of revascularization when compared to medical therapy in patients with
stable and unstable coronary artery disease
among the risks of the natural course of coronary artery disease placed
into perspective with the results of recently reported trials having
investigated hard end-points in revascularized patients with coronary
download time 02 Min 02 seconds at 28.8 kbs: only for patient consumers
update, 26. Oct. 2000, have a look at my comments about FRISC II
following discussion addresses specifically the questions, whether
treated with revascularization have a better outcome in terms of cardiac
death and acute myocardial infarction than medically treated patients,
angiography is a reliable tool to predict the functional severity and
prognostic impact of coronary narrowing and the caveats we should know
from the presence of coronary thrombus in patients undergoing
||what might be
the impact of non-invasive stress testing in patients with known or
suspected coronary artery disease.
the success achieved by revascularization in perspective with the
natural course of coronary artery disease derived from historical groups
of patients with known coronary anatomy and normal or near normal left
ventricular function, the net benefit in terms of risk reduction for
cardiac death and acute myocardial infarction appears not quite
impressive. Especially in low to medium risk patients treated with
Stents/PTCA further randomized studies are urgently needed, in order to
establish, which patients may benefit from revascularization.
review, however, excludes patients with severely impaired left
ventricular function (e.g.< 30%), a subgroup of patients, for whom
revascularization (especially when CABG is performed) has
view of extensively used revascularization procedures despite risk
reductions achieved with a modern medical treatment, specifically
aspirin, statins, betablockers and abciximab, it seems correct to
compare medical treatment with revascularization in specific subsets of
patients. Some studies of that kind are underway, although the numbers
of patients enrolled are relatively small.
thought, that the risk of coronary artery disease (CAD) has been
substantially reduced using either medical treatment or
revascularization procedures with subsequent risk reduction for hard
endpoints in all subsets of the clinical expressions of CAD over time.
However, no large-scale trials compared the merits of revascularization
in relation to medical therapy with aspirin, betablockers and statins in
stable CAD and additional abciximab in medically treated patients with
unstable coronary syndromes. Such trials are urgently needed, because
revascularization may be hazardous in comparison to medical therapy in
specific subsets of patients with stable and unstable CAD.
trials comparing different strategies for the treatment of CAD were
inprecise in reporting base-line characteristics of patients especially
with regard to left ventricular function, which is still the most
important variable for the risk stratification in all subsets of CAD
(stable and unstable).
of cardiac death (CD) and acute myocardial infarction (AMI) in a
population of subjects with angiographically documented CAD could be
expressed in absolute terms, e.g. death and infarction rates per 1000
patients per year and with statement of left ventricular function and
the number of diseased vessels, the degree of vessel obstruction and the
site of obstruction in order to allow for appropriate comparison of
outcomes among different large-scale randomized trials.
of reporting scientific data was observed mainly in the CASS-registry1.
From this study, firm evidence was derived in that CABG is essentially
benefical in comparison to medically treated subjects only if
impaired left ventricular function or
angina (class III-IV) in patients with normal left ventricular function
was noted at baseline.
do not dispose from large-scale trials comparing medical with
revascularization therapy, we may use surrogate control groups derived
from historical trials having looked at the natural outcome of patients
with different expressions of CAD in order to place the merits of
revascularization in perspective.
Stable coronary syndromes.
fibrous plaque with small lipid core: low risk for rupture (=acute
coronary syndrome) despite high degree reduction of luminal area.
control group (DUKE registry): Absolute
death rates for medically treated patients with significant coronary
narrowing (>75%) and normal or near normal left ventricular function
(ejection fraction >50%) during a five year follow-up period15
were 18% for single vessel CAD (1VD, N=307), 28% for 2VD (N=309),
46% for 3VD (N=521) and 39% for 2+3VD (multi vessel disease, MVD, N=830
with 62% of patients having 3 VD). The annual incidence for CD was
12/1000/year in 1 VD, 20/1000/year in 2 VD, 48/1000/year in 3 VD and the
corresponding numbers for AMI were 24, 36 and 44 respectively with
corresponding numbers for the combined risk for CD and AMI of 36, 56 and
92 respectively (table 1). The CD rate was 38/1000/year for MVD. The
corresponding number for AMI rate was 40, the combined number (CD and
AMI rates) was 78/1000/year15.
Of note, the overall CD rate of 38/1000/y in the DUKE registry was quite
comparable to the CD rate of 34/1000/year reported in the CASS registry1,
a number taken from the observational arm of medically treated patients
with follow-up of 5 years and having MVD (N=930, 71% of patients having
1: The natural course of CAD, Duke registry15
CD: denotes cardiac
death. AMI: denotes acute myocardial infarction. VD: denotes vessel
registry numbers were derived from patients who did not take aspirin or
statins. Aspirin may reduce cardiac death rates by 3/1000 treated
patients4 , statins by 7/1000 treated patients3
with an expected overall effect in absolute risk reduction of CD rates
of about 10/1000 treated patients. Corresponding numbers for the risk
reduction of developing non-fatal AMI are 7/1000/year for aspirin4
and 14/1000/year for statins3.
these numbers in the 5 year follow-up DUKE medically treated patient
registry15 with MVD e.g. we would expect an anually CD rate
of 28/1000 and an AMI rate of 19/1000 in medically treated patients and
an absolute risk for CD and AMI rates of 47/1000/year instead of
78/1000/year. Such numbers could serve as a reference to which any type
of intervention in patients with CAD, normal or near normal left
ventricular function at rest and stable coronary disease could be
scale randomized trials have been reported in the past few years
addressing the question, whether CABG offers advantages in comparison to
PTCA in terms of risk reduction for hard end points in patients with
multivessel disease2,11,12 and found no difference for hard
event outcomes in patients with multi-vessel CAD except for a strong
favorisation of CABG over PTCA in patients using anti-diabetic
medication11. None of these studies reported the absolute
death and AMI rates in relation to the number of diseased vessels and
impaired left ventricular function precisely. Moreover, there is no
large scale randomized trial comparing medical therapy with
revascularization in patients with normal left ventricular function.
Importantly, patients who refused to be randomized to revascularization
had a statistically better outcome for cardiac death rates than their
group (DUKE registry 1969-78) versus CABG or PTCA
and AMI rates for patients with MVD and normal or near normal left
ventricular function can be derived from the recently reported CABG
versus PTCA treatment trials having included a total of 2285 patients
during a follow- up time of slightly more than one year2,11,12.
In these trials, CD rates of revascularized patients with MVD was
15/1000/ year, AMI rate 31/1000/year and combined rates of CD and AMI
46/1000/year. Thus, in comparison to the reference group taken from the
DUKE registry, revascularization can be expected to reduce CD rates by
about 23/1000/year and AMI rates by 9/1000/year. It must be emphasized
however, that about 65% of medically treated patients had 3 VD in the
DUKE registry, whereas 3 VD was present in only about 40% of patients
randomized in the ERACI and EAST trial (percent of patients with 3VD are
not available from the published report of the BARI trial) and that none
of the patients from the DUKE registry had a medical therapy with
aspirin and statins.
compilation of the effect of CABG in randomized trials compared to
medical therapy was published in the Lancet in 19946. In
these 2649 observationally studied patients the medically treated
patients had significantly lower event rates for the combined outcome of
CD and AMI (80/1000 vs 116/1000, p<0.001) at the follow-up of one
year. At a 5 year follow-up, the overall AMI rate was identical for CABG
and medically treated patients (28,4/1000 vs 29,8/1000) whereas cardiac
mortality was significantly lower in CABG patients having saved 12 lives
in 1000 treated patients during a follow-up period of one year (20/1000
vs 32/1000). Thus, CABG offered an overall advantage for the reduction
of CD but not AMI rates, but thousands of patients had to be treated in
order to show a small but statistically significant benefit of
revascularization over medical treatment, despite the fact, that most
medically treated patients did not take aspirin (about 80%) and no
patient took statins.
EPISTENT trial18 compared 2399 multicenter patients from
Canada and the U.S. and showed a dramatic risk reduction with ReoPro of
54% for the combined end point of CD, AMI or need for urgent
revascularization at 30 days of follow-up in a population with various
expression of CAD, mainly about 35% with UAP (<48 hours) and 16% with
AMI (<7 days). The combined end point of hard events at 30 days was
defined as 1. cardiac death, 2. non-fatal transmural infarction, and 3.
large non-Q wave myocardial infarction (CK elevation >5 times). 4.
Small non-Q wave myocardial infarctions (CK elevation 3-5 times) were
considered negligible and not included in the main analysis. However,
patients with periprocedural small myocardial infarctions have a poor
outcome10 and should be treated like acute myocardial
infarction (see below: section entitled thrombus). The number of hard
endpoints (CD or any size of AMI) at 30 days of follow-up was 102/1000
for revasularized Stent + placebo patients (without ReoPro) and 48/1000
in patients with Stent + abciximab therapy. Placing these results
into perspective with the results reported by Yusuf6, the
addition of ReoPro (Abciximab) prevented the hazards due to extensively
performed revascularization prodecures with an achievement of comparable
outcome in hard end-points among patients treated between 1972 and 1984
with CABG (48/1000/year) or medically (62/1000/year) and keeping in mind
that the EPISTENT hard events were derived from an only 30 days
follow-up. Furthermore, the excessively high rate of CD and AMI of
102/1000/year in the EPISTENT trial with regard to the Stent + placebo
group versus 62/1000/y hard events in the historical medically treated
group with 2 or 3 VD (see Table 1) and 88/1000/y of hard events in a
large number of patients with UAP treated medically before 1990 (Table
2) raises some concerns about the safety of coronary interventions in
patients without the use of ReoPro.
groups versus PTCA
to compare medical therapy with PTCA in randomized trials were rare so
far. The RITA-2 trial adds evidence to the concern about the
safety of PTCA in a large-scale randomized trial (N=1018) having
included patients with mainly mild coronary artery disease (60% had
single vessel CAD) and found a statistically significant excess rate for
CD and AMI (6.3% vs 3.3% at 2.7 years of follow-up, p=0.02)46.
The medically treated arm of patients in this trial (follow-up 2.7
years) had a hard event rate (CD + non fatal AMI) of 9/1000/y,
significantly lower when compared to the patients treated with PTCA
(19/1000/y). Thus, although PTCA may offer immediate, but often (40%)
not constant symptom relief to coronary patients, it may have a negative
impact on their prognosis.
landmark study (AVERT-trial)
reported in November 1998 at the American Heart Meeting in Dallas, Texas
compared the effect of a) high dose Atorvastatin to b) PTCA and usual
medical therapy in 341 patients with mainly single vessel disease and
normal left ventricular function who were candidates for PTCA and with
follow-up of 18 months. The goal of the intensive lipid therapy was to
achieve an LDL-level below 2.6 mmol/l. In this study, 87% of the medical
group patients remained free of cardiovascular events during follow-up.
The percent of cardiovascular events - defined as nonfatal MI, bypass
surgery, PTCA, and worsening angina - was 13% in the medical and 21% in
the PTCA group (p NS).
ACIP trial50 recently published in Circulation, the two year
outcome (cardiac death or non-fatal MI) of patients randomized to either
early revascularization or ischemia-guided maximal medical therapy were
not statistically significant.From the same investigators comes a
recently bublished cost-effective analysis (Am J Cardiol
1999;84:1311-1316):"Our study is the first to compare costs
associated with randomly assigned initial treatment strategies for
patients with chronic [coronary artery disease]," Dr. Knatterud and
colleagues say. "These treatments are routinely used with choices
representing personal preferences in the absence of controlled trial
data."The team concludes that "...early revascularization with
long-term follow-up may prove to be cost-effective while improving
quality of life during a patient's more productive years."
view of the favorable results of these pilot-type trials outlined above
(eg, short follow up, small numbers of patients and events), larger and
longer definitive prognostic trials are clearly required. To this end,
the National Heart Lung Blood Institute is initiating two large scale
intermediate duration of follow up (5-6 years) in 6000 and 3260 patients
respectively, where intensive medical therapy is compared with
Unstable coronary syndromes
Lipid rich plaque with large lipid core and thin fibrous cap: high
risk of rupture (=acute coronary syndrome) despite insignifcant
(<50%) degree reduction of luminal area..
clot versus red clot:
with unstable angina pectoris (UAP) class III (Braunwald classification)
have frequently white clot thrombus (platelet rich thrombus), which can
normally not be dissolved by fibrinolytic agents used to dissolve red
thrombus, which is very frequent in patients with transmural AMI21.
Developement of UAP on the base of disrupted lipid-rich plaques leads to
aggregation of thrombocytes or to white clot thrombosis with subsequent
increase in vasomotor tone (vasospasm) due to a release of serotonin and
thromboxane A222. Thus UAP and possibly non-Q AMI represent a
white clot problem, which can be managed by medical therapy using
aspirin, heparin, betablockers and glycoprotein IIb/IIIa inhibitors like
abciximab or tirofiban and statins, with a risk reduction of any cardiac
event at 3 months by about 50% as shown previously for the combined use
of aspirin and heparin 23 and recently by an additional risk
reductin of 27% when tirofiban is added to a conventional aspirin and
heparin treatment with 8.7 deaths or myocardial infarctions at 30 days
and 12.3 deaths or myocardial infarctions at 6 months for the active
treatment with tirofiban, aspirin and heparin45.
patients with acute coronary syndromes it is known, that the culprit
lesion after successful thrombolysis is usually not severe (mean value
56%30,47) what further underlines the evidence that UAP and
acute myocardial infarction is a clot and unstable plaque problem on the
top of a usually not severe coronary narrowing. A very exciting albeit
small study, the recently published TIMI 14 Trial in Circulation 54
has shown, that combining accelerated TPA with abciximab resulted in a
TIMI 3 flow in 76% of patients at 90 minutes, a results that is
perfectly comparable to results previously reported for early
revascularisation and that this combination of thrombo- and fibrinolysis
resolves coronary thrombus on top of mainly non-obstructive leasons.
in unstable angina:
recently used Abciximab (ReoPro) in unstable coronary syndromes in
patients revascularized with PTCA or Stent24,25,26 reduces
the risk of in hospital CD, AMI and urgent revascularization rates,
these rates remain high (about 65/1000/6 months CD+AMI with and about
130/1000/6 months without RePro in the EPIC24 and EPILOG25
trial) and have not been tested in randomized trials against a medical
strategy using aspirin, heparin, abciximab, statins and risk
stratification with perfusion myocardial scintigraphy in medically
stabilized patients. ReoPro in unstable angina: Although recently used
Abciximab (ReoPro) in unstable coronary syndromes in patients
revascularized with PTCA or Stent24,25,26 reduces the risk of
in hospital CD, AMI and urgent revascularization rates, these rates
remain high (about 65/1000/6 months CD+AMI with and about 130/1000/6
months without RePro in the EPIC24 and EPILOG25
trial) and have not been tested in randomized trials against a medical
strategy using aspirin, heparin, abciximab, statins and risk
stratification with perfusion myocardial scintigraphy in medically
studies having collected data in patients studied between 1980-88, where
both aspirin and revascularization were used far less frequently than
today, we can derive a „natural course„ group from 4 studies31,32,
33,34 having treated 1722 patients for UAP with an overall CD+AMI
rate of 88/1000/year (table 2). Moreover, this comparison shows an
excess risk for patients with UAP treated with revascularization before
the use of ReoPro when compared to medically treated patients
(130/1000/6 months versus 88/1000/year) which rises serious concerns
about the use of revascularization in UAP, an argument that underlines
the importance of the idea, that broadly used revascularization
procedures should be compared in randomized trials with medical therapy
in specific subsets of patients with CAD.
in unstable aninga
OASIS studies reported at the ESC-meeting in Vienna 1998: More evidence,
about what a conservative approach can do in patients treated for UAP
comes from the OASIS trials (combined data from the OASIS pilot study
and the large OASIS II study), which was reported by Salim Yusuf. In
these trials having compared the potential benefits of the specific
thrombin inhibitor hirudin vs heparin in 11049 patients with UAP, 6% of
patients had early refractory angina during medical therapy and only a
total of 7% of patients had to undergo early revascularization (< 7
days from the onset of symptoms). Despite this very low rate of coronary
interventions, the 30 day combined endpoint for CD and AMI was 73/1000
(68/1000 in patients randomized to hirudin). These patients, however,
were not treated with GPIIa/IIIb inhibitors and compare well with the
outcome in patients treated with ReoPro in the EPIC24 and
EPILOG25 trials. Since it is known, that beyond 4-8 weeks
after the onset of UAP CD and AMI do rarely occur, we can expect that
the follow up data (e.g. 6 months) of these patients in the OASIS
studies will not be changed substantially.
very important and large scale study in the context of nonQ-wave
instable coronary syndromes was reported in the New England Journal of
Medicine recently49 comparing eptifibatide (a GP IIb/IIIa
inhibitor) to placebo in 9461 patients recruited in the US, in Latin
American and in Western and Eastern Europe. This trial showed many
interesting results with regard to different baseline characteristics of
patients and use of revascularization. with respect to the
different regions. Subgroup analyses with respect to outcome and cost
efficiency are currently underway. However, preliminary data from the US
New England and the British cohort (both traditionally using invasive
strategies much less frequently than most remainders) showed these
regions to be most effective in terms of costs per live saved.
CD: denotes cardiac
death. AMI: denotes acute myocardial infarction. N: denotes numbers of
from the VANQWISH trial
view is underscored by the result of the VANQWISH trial which found a
significantly higher death rate in patients with early invasive strategy
in nonQ-AMI as compared to a conservative strategy17 at one
year of follow-up (N=920: CD 49 in conservative versus 61 in invasive
strategy group, non fatal AMI 26 versus 36). It must be emphasized
however, that most adverse outcomes int the invasive strategy group were
due to high event rates in patients treated with CABG (11%) and not with
PTCA (0%). Interestingly, in the invasive group, which did not undergo
non-invasive risk assessment N=442), the one-year CD and AMI were
highest in the subgroup not having undergone revascularization (N=204 vs
238, CD 31 vs 21 and AMI 25 vs 11) which may be explained by the failure
of coronary angiography to risk stratify patients correctly based on
plaque morphology only. It will be left to the future analysis, what
will be the exact impact of the VANQWISH trial on medical practice.
Caveat from the VANQWISH trial: This view is underscored by the result
of the VANQWISH trial which found a significantly higher death rate in
patients with early invasive strategy in nonQ-AMI as compared to a
conservative strategy17 at one year of follow-up (N=920: CD
49 in conservative versus 61 in invasive strategy group, non fatal AMI
26 versus 36). It must be emphasized however, that most adverse outcomes
int the invasive strategy group were due to high event rates in patients
treated with CABG (11%) and not with PTCA (0%). Interestingly, in the
invasive group, which did not undergo non-invasive risk assessment
N=442), the one-year CD and AMI were highest in the subgroup not having
undergone revascularization (N=204 vs 238, CD 31 vs 21 and AMI 25 vs 11)
which may be explained by the failure of coronary angiography to risk
stratify patients correctly based on plaque morphology only. It will be
left to the future analysis, what will be the exact impact of the
VANQWISH trial on medical practice.
results are supported by the 49, where a strategy comparing
revascularisation of AMI patients (N=1008) with documented ischemia
(ST-segment depression during exercise) had statistically significant
lower event rates (reinfarction 5.6% vs 10.5%) if revascularized in
comparison to patients with post-infarct ischemia and a conservative
strategy. In contrast to the VANQWISH trial however, this study did not
allow to assess the benefit from non-invasive testing to detect patients
who most likely may benefit from revascularization (=those with ischemia
small but provocative pilot study53 examined the effect of
intensive medical therapy compared with coronary angioplasty, both
directed at suppressing ischemia in survivors of myocardial infarction.
Each patient had large perfusion defects on Thallium scintigraphy which
was reduced similarly in both treatment groups and with comparable event
rates during follow-up
this evidence prompts the argument that risk reduction of CD and AMI
rates using revascularization procedures may not reach statistically
relevant proportions in future studies comparing the outcome especially
in patients under optimal medical therapy even if MVD is present. In
view of the relatively high number of hard event rates reported even in
the most recent trials using PTCA, Stent implantation and ReoPro18,
it seems reasonable to argue, that the time for testing lipid lowering
and aspirin and ReoPro versus revascularization has come.
IV was presented at ESC, Amsterdam 2000
stands for "GLOBAL USE OF STRATEGIES TO OPEN OCCLUDED ARTERIES IN
ACUTE CORONARY SYNDROMES". In this large trial having included 7800
patients with unstable angina and nonq-wave myocardial infarctions not
deemed eligible for percutaneouy interventions, the hypothesis was
tested, that adding the potent platelet inhibitor ABCIXIMAB on top of
aspirin, heparin and betablockers would reduce hard end points at 30
days, however it did not. The authors expected an event rate for acute
MI and cardiac death of 11% at 30 days, but observed only 8% events
irrespective of Abciximab. The reasons for this unsuspected findings
will not be clarified, until the definitive results will be published.
in favour of aggressive early strategies in unstable coronary syndromes
more aggressive approach is generally accepted in high risk patients not
responding to medical therapy, exemplified in the TIMI IIIb database
substudy of patients not responding to medical therapy, mainly patients
with ongoing chest pain, ST-depression, and older age55 .
recently, the FRISC II study involving 2457 patients with UAP oder non Q
AMI was presented in the Lancet in 199956 6
and has shown an impressive risk reduction in favour of early invasive
revascularization versus initial ischemia guided therapy. After a follow
up of 6 months the risk for death and non fatal AMI was 9,4% in the
invasive versus 12,1% in the medical treatment arm (p=0.031).
Why was the risk of death and non fatal AMI higher for medically treated
patients when compared to previous studies (see Table 2 !)?
Why was the risk of primary end points not reduced in women ?
At least 10% of patients in the invasive arm received ReoPro outside of
the study protocol, which was not the case in the conservative arm.
Around 25% of patients had previous myocardial infarction. In these
patients, risk stratification based on ECG stress tests is often
hampered by baseline changes in the rest ECG. Moreover, the cutoff value
for exercise induced ischemia was set at a > 3 mm ST depression cut
off point (!).
Here a closer look at FRISC II in comparison to VANQWISH: The
conservative arm of Vanqwish (N=458) and the conservative arm
ofFRISC II (N=1235) may be compared: Age 62 vs 65 almost
identical, men 97% vs 68%, revascularisation after 30 days
33% vs 22%, revascularisation after 6 months 38%(?) vs 39%, CD
and AMI after 1 year (Vanqwish) in 97% of men 10.7%, after
6 months (FRISC II) only in men 13.9% (women had a better
outcome with respect to CD and AMI in the conservative vs
invasive strategy (8.3% vs 10.5% !!!). Indication for switch to
invasive arm: pathological Thallium scan (Vanqwish),
ST-depresssion over 3.0 mm (sic !!!) in FRISC II. In other
words: in FRISC II the male patients in the conservative arm
were revascularized too late because of too tough ischemia
criteria. Moreover: in patients randomized to Dalteparin, there
was no significant difference in outcome for the combined
endpoint of CD+AMI in the conservative and invasive arm of that
In a study
published in the NEJM in the first issue of November 1999 a rather small
number of patients were randomized either to primary PTCA (N=194) or
Streptokinase (N=201) in the setting of acute myocardial infarction. In
the short as well as in the long term (5 years) these Dutch authors
observed a significantly and sustained better outcome with regard to
cardiac death and non fatal AMI in the patients treated with early PTCA57.
and prognostic problems inherent to coronary angiography
the angiographer point of view, stenosis >70% are functionally
relevant, whereas stenosis of 50(60)-70% are probably functionally
relevant. The correct interpretation of coronary stenosis is hampered
for several reasons: a) collateral and functionally relevant
subepicardial coronary flow cannot be reliably assessed by CA, b)
epi-stenotic thrombus is frequently not diagnosed by CA, c) the degree
of stenosis is increased during physical exercise, and d) the degree of
stenosis is a rather poor predictor for subsequent cardiac events
flow may be assessed by CA. In one study, visible epicardial flow by CA
in patients with acute anterior myocardial infarction was associated
with in-hospital death rates of 8% with versus 23% in patients
without angiographyically visible collateral flow respectively14.
Subepicardial collateral flow is not visible with routine CA or if
visible, not always functionally relevant and may yield completely
cardioprotective dimensions when assessed by myocardial contrast
echocardiography during acute coronary occlusion with PTCA13.
Thus, oculo-stenotic reflexes may lead to revascularization of
angiographically relevant but functionally irrelevant coronary artery
thrombus is frequently present in patients with CAD (e.g. in 69% in
patients with recent AMI, 54% in unstable angina and 29% in stable
angina) 16. The sensitivity to detect intracoronary thrombus
by CA is 65% and the negative predictive value is 58%16. In
patients with intracoronary thrombus, revascularization using PTCA,
especially stent-implantation, was defined as the worst ennemy of the
interventional cardiologist and is strongly underestimated by coronary
angiography16. Relevant CK-elevations (> 3 times normal)
occur in up to 15% of patients having undergone PTCA, should be treated
as myocardial infarction (irrespective of ECG-findings) and have a poor
prognostic outcome, like acute myocardial infarctions10. The
in-hospital death, AMI and emergency CABG rate was 14% in patients with
and 2% in patients without intracoronary thrombus having undergone
revascularization with PTCA20, where 50 (68%) out of 74
thrombi detected by angioscopy where missed by angiography.
Degree of stenosis:
vasomotor tone has been recognized to play a crucial role in determining
the ischemic threshold and the occurence of spontaneous and
exercise-induced myocardial ischemia9. Normal coronary
vessels show exercise-induced dilation (+14% lumen diameter) which is
further enhanced after sublingual nitroglycerin (+32% lumen diameter).
In contrast, stenosis show exercise-induced vasoconstriction (-28% lumen
diameter), which is partially reversed after sublingual nitroglycerin
(+8% lumen diameter). Importantly, there is a significant, inverse
correlation between the number of cardiovascular risk factors and mean
exercise-induced percent change in coronary luminal area. Newly
introduced intracoronary pressure gradient estimations are costly
(around 1000 US $ per catheter) and reflect the degree of stenosis after
maximal coronary dilatation with nitroglycerin; thus, this method may
not be suited to identify the culprit lesion responsible for patients
symptoms during physical acitivity.
Prediction of coronary events:
the more severe a stenosis is found at the time of CA, the higher is the
subsequent risk for CD and AMI, thus sealing high grade plaques with
PTCA is thought to stabilize the plaque and helps to avoid future
cardiac events. The idea of plaque sealing has, to my knowledge, not
specifically been tested in clinical trials.
|The risk for
subsequent CD and AMI can be assessed by left ventricular function
studies, by the extent score (number of vessels exhibiting a 5 to
75% stenosis in a 15 segment model of the coronary tree), by the
number of coronary vessels with stenosis > 75% (e.g. Gensini and
Friesinger score=stenosis score), by nuclear imaging and by
stress-echocardiography. Comparing left ventricular function, the
extent score and the stenosis score in 312 patients with follow-up
over a mean period of 3.4 years, Moise35 found (using Cox
multivariate analysis) that left ventricular function was the best
predictor for CD (chi-square 17.78), followed by the extent score
(chi-square 9.87) and the stenosis score (chi-square 6.61). The only
statistically relevant predictors of the combinded endpoints (CD,
AMI and unstable angina) were left ventricular function (chi-square
12.02) and the extent score (chi-square 8.12), whereas the stenosis
score was statistically not significant in this historical
population with known CAD and without aspirin and statin medication.
Thus, it is the number of minimal to moderate plaques found in the
coronary tree that more precisely defines the patients risk for
subsequent cardiac hard-point events more than the presence of
severe coronary obstruction. Of note, left ventricular function was
found to be the best predictor for subsequent cardiac events, over
another study38, 17 patients with AMI were identified
with previous coronary angiograms. Only in 4 patients, the previous
stenosis was found to have a degree of obstruction > 70%.
location of future AMI was correctly predicted by SestaMIBI
myocardial perfusion imaging in 63% of patients37a and by
stress-echocardiography in 46%37b.
modern pathophysiological concept explaining these findings has been
described extensively elsewhere36. In brief (see figures
above), mainly lipid-rich (unstable) plaques may cause disruption or
thrombus formation on the base of intimal erosion with subsequently
increased risk for CD, AMI and unstable angina. These plaques are
rarely obstructive but may appear obstructive by thrombus formation
on coronary angiography.
these observational studies we are confronted with the
counterintuitive and remarkable conclusions, that CA does not
accurately predict the site of future coronary events, that plaque
sealing most often is performed in sites where future cardiac events
may not occur and that aspirin and statins appear as a valuable,
low-cost and scientifically approved means for plaque sealing
(stabilization) in the whole coronary tree.
view of the potential hazards of plaque sealing of coronary vessels
without documented ischemia, the concept of plaque sealing should be
abandoned except for high risk stenosis (proximal > 90% stenosis
in two of the main coronary vessels). Plaque sealing is so far just
an idea, which was never tested in randomized trials.
did not significantly reduce CD rates in comparison with medical
therapy for any subset of severity of CAD reported from an
observational trial including 3557 patients with medical therapy and
2626 patients having undergone PTCA39 during a follow-up
time of 5 years.
myocardial perfusion scintigraphy has been shown to yield
incremental information with regard to cardiac prognosis over
clinical and coronary angiographic data44.
Cedars Sinai Medical
Center: great experience with myocardial perfusion imaging
clinical point of view, we need to know, which patients may benefit from
revascularization and in which patients we can safely avoid coronary
angiography. Because of the importance of this issue for public health,
only large scale trials should be addressed to answer this question.
recently published in Circulation8, 5183 patients followed up
for a mean of 642 days and assessed by myocardial perfusion
scintigraphy, showed a death rate of 3/1000/year and an AMI rate of
5/1000/year in normal scans (combined 9/1000/year) and a death death
rate of 8/1000/year and an AMI rate of 27/1000/year in mildly abnormal
scintigraphic scans (combined CD+AMI rates of 35/1000/year). From this
large-scale trial, we can argue with keeping mortality and AMI rates
reported from recently published revascularization trials in mind, that
no revascularization modality may reduce cardiac risk in this low-risk
population. Similar results were published recently for the
stress-echocardiography with dobutamine and atropine48.
Moreover, the Hachamovich study adds important scientific information to
the concept of risk reduction by ischmia guided therapy.
efficacy (negative predictive values >90%) in risk assessment using
non-invasive testing has been reported in patients with unstable
concept of performing CA only in patients with persistent coronary
symptoms despite medical therapy, in patients with relevant ischemia as
assessed by non-invasive testing or in patients with relevant reductions
of left ventricular function (e.g. EF<30%) is in agreement with the
official guidelines of the European Society of Cardiology40,42
having been published for the management of stable angina pectoris and
acute myocardial infarction. Moreover, there is a perception of coronary
intervention overuse also in patients post AMI, as pointed out recently
in an editorial in the European Journal of Cardiology28.
assessment, exercise testing, myocardial perfusion scintigraphy and
stress echocardiography offer important clues to the risk management
of patients with suspected or proven coronary artery disease
presenting with stable and unstable coronary syndromes and should be
used extensively to identify patients with low risk for subsequent
cardiac death and myocardial infarction in order to avoid
potentially hazardous revascularizations of „dangerous"
coronary artery stenoses as defined by coronary angiography.
several caveats are known to the medical community inherent to the
invasive approach of CAD treatment, and keeping in mind the high
efficacy of stabilizing patients in terms of subsequent risk of
cardiac death and acute myocardial infarction using medical
treatment and the „help" of non-invasive risk stratification
strategies, the time to test the outcome of CAD patients in
large-scale studies comparing invasive versus medical strategies
addressing mainly patients with normal or near normal left
ventricular function, which is the most powerful discriminator for
subsequent cardiac risk, has come.
data reported in this review place the enthusiasm of invasively
acting cardiologists treating patients with various clinical
expressions of coronary artery disease in perspective and furnishes
arguments to a maximal medical, yet conservative approach in the
management of patients with acceptable cardiac risk as assessed by
clinical evaluation and non-invasive testing.
must be emphasized, however, that the recent progress in term of
risk reduction achieved by invasive strategies using the adjuncts
of GPIIa/IIIb inhibitors and Stent implantation is dramatic (up to
- 50%). Nevertheless, it must be proven in the future, that these
strategies do not only offset the harm of too extensively
used revascularization as performed recently (not having used
these adjuncts) and remain cost efficient and prognostically
relevant in comparison to an aggressive, yet conservative approach
offered to patients suffering from acute and chronic coronary
opinion leaders, even when acting as interventional cardiologists,
are clearly supporting these conclusions and await future
randomized trials comparing medical vs invasive therapeutic
stratagies in coronary artery disease. In the short come, we
expect stenting and the use of GP IIb/IIIa receptor blockers to
have an overwhelming use. Awaiting trials in the farer future, the
question is: " Non-invasive therapy might be better. How soon
will this be finally proven ?".
this review is a subject of
continuous reevaluation furnished by newer scientific reports, has not
been published anywhere, is not peer reviewed and is meant as a paper
open for debate.
klick here to send a message: firstname.lastname@example.org
CASS registry. Kaiser GC et al. J Thorac Cardiovasc Surg 1985;89:513.
EAST Trial. AJC 1997;79:1453.
4S Trial. Lancet 1994;344:1383.
SAPAT study. Juul-Möller, Lancet 1992;340:1421-1425.
GABI trial. Eur Heart H 1996;17:1192.
Yusuf. Lancet 1994;344:563.
DUKE registry. Circulation 1994;89:2015.
Myocardial perfusion scintigraphy for prediction of death and AMI.
Coronary stenosis vasoconstriction: impact on myocardial ischemia. Eur
Heart J 1997;18:1853.
Myonecrosis. JACC 1998;31:241.
BARI trial. Circulation 1997;96:2162.
ERACI trial. JACC 1996;27:1178.
Collaterals. Am J Cardiol 1997;79:1329.
Collaterals and death in acute anterior AMI. N. Perez et al. JACC
DUKE registry of patients having undergone CA between1969-1978. Harris
and coworkers, Circulation 1980;62:718.
Bertrand. Data reported at ESC 1997.
VANQWISH trial, NEJM 98;25:338.
The Epistent Trial. Lancet, 1998;352:87-92.
AVERT trial, AJC97;80:1130: 341 patients open label randozimed trial to
atorvastatin or PTCA with outcome measurements at 18 months.
Initial results presented at AHA meeting Nov 1998.
White CJ et al. Coronary thrombi increase PTCA risk. Circulation
Mizuno et al. NEJM 1992;326:287.
Willerson et al. Circulation 1980; 80:198.
Theroud et al. NEJM 1992;327:141.
EPIC trial. JACC 1997;30:149-56.
EPILOG trial. NEJM 1997;336:1689.
CAPTURE trial. Lancet 1997;349:1429-35.
Prognostic value of predischarge dipyridamole technetium 99m sestamibi
myocardial tomography in medically treated patients with unstable
angina. Am Heart J (United States), Oct 1995, 130(4) p734-40. Stratmann
H et al.
Prognostic evaluation of patients after myocardial infarction:
incremental value of sestamibi single-photon emission computed
tomography and echocardiography. J Nucl Cardiol , 1997;4:117-24. Zanco P
Prognostic value of exercise 201Tl tomography in patients treated with
thrombolytic therapy during acute myocardial infarction. Circulation
(United States), Dec 1 1996, 94(11) p2735-42. Dakik H et al.
Brown B et al. Circulation 1986;73:653.
Swahn E et al. Am J Cardiol 1987;59:208.
Severi S et al. Eur Heart J 1988;9:441.
Madsen J et al. Eur Heart J 1988;9:611.
Nyman L et al. RISC study group. Am Heart J 1992;123:324.
Moise A et al. Clinical and angiographic correlates and prognostic
significance of the coronary extent score. Am J Cardiol 1988;61:1255.
Falk E et al. Coronary plaque disruption. Circulation 1995;92:657.
Trabulo M. Predicitve value of coronary angiography in the localization
of arterial lesions responsible for future infarcts to the myocardium.
Rev Port Cardiol 1996;15:11.
G.Miller. Relation between perfusion defects on stress technetium-99m
sestamibi SPECT scintigraphy and the location of a subsequent acute
myocardial infarction Am J Cardiol 1996;78:26.
Varga A. Does stress testing and coronary angiography predict the site
of future myocardial infarction? A large-scale multicenter study. EPIC
(Echo Persantine International Cooperative) and EDIC (Echo Dobutamine
International Cooperative) study groups. J Am Coll Cardiol 1996, 28, 45.
Mark D. Continuing evolution of therapy for coronary artery disease.
Initial results from the era of coronary angioplasty. Circulation
Guidelines. Management of stable angina pectoris. Recommendations of the
Task Force of the European Society of Cardiology. Eur Heart J
MIRACL Study. Atorvastatin in UAP and nonQ-AMI vs placebo. Am J Cardiol
Guidelines. Acute myocardial infarction: pre-hospital and in-hospital
management. Eur Heart J 1996;17:43.
Naylor J. et al. Coronary angiography and revascularization after acute
myocardial infarction: which rate is right?. Eur J Cardiol 1998;19:529.
Scintigraphy better than CA. Search.
Myocardial infarction inhibition of the platelet glycoprotein IIb/IIIa
receptor with tirofiban in unstable angina and non-q-wave infarction. N
Engl J Med 1998;338:1488-97.
RITA-2 Trial. Lancet 1997;350:461.
E. Lell et al. Relevanz nicht signifikanter proximaler Koronarstenosen -
klinische Bedeutung im Langzeitverlauf. Abstract SGK 1998. Schweiz Med
Wochenschr 1998;128:Suppl 97.
Chuah SC. Role of dobutamine stress echocardiography in predicting
outcome in 860 patients with known or suspected coronary artery disease.
PURSUIT Trial. NEJM 1998;339:436.
Davies et al. ACIP trial. Circulation 1997;95:2037.
SOCRATES study: Study of Coronary Revascularization and Therapeutic
COURAGE study: Clinical outcomes Utilization Revascularization and
Aggressive druG Evaluation
Dakik H, et al. Intensive medical therapy vs PTCA in survivors of
myocardial infarction. Circulation 1998;98:2017.
Abciximab facilitates the rate and extent of thrombolysis. E Braunwald
et al. Circulation.1999;99:2720-2732.)
Factors associated with failure of medical therapy in patients with
unstable angina and non Q wave myocardial infarction. Eur Heart J
FRISC II study. Lancet 1999;354:78-15.
N Engl J Med 1999;341:1413-9
and Internet files:
TITLE: Influence of collateral circulation on in-hospital death from
anterior acute myocardial infarction.
SOURCE: J Am Coll Cardiol (United States), Mar 1 1998, 31(3) p512-8
Perez-Castellano N; Garcia EJ; Abeytua M; Soriano J; Serrano JA; Elizaga
J; Botas J; Lopez-Sendon JL; Delcan JL
OBJECTIVES: Our purpose was to study whether the in-hospital prognosis
of anterior acute myocardial infarction (AMI) is influenced by
preexistent collateral circulation to the infarct-related artery.
BACKGROUND: Collateral circulation exerts beneficial influences on the
clinical course after AMI, but demonstration of improved survival is
lacking. METHODS: We studied 238 consecutive patients with anterior AMI
treated by primary angioplasty within the first 6 h of the onset of
symptoms. Fifty-eight patients with basal Thrombolysis in Myocardial
Infarction (TIMI) flow 1 in the infarct-related artery or with
inadequate documentation of collateral circulation were excluded.
Collateral channels to the infarct-related artery before angioplasty
were angiographically assessed, establishing two groups: 115 patients
(64%) without collateral vessels (group A) and 65 patients (36%) with
collateral vessels (group B). RESULTS: There were no differences in
baseline characteristics between groups A and B, except for the greater
prevalence of previous angina in group B (15% vs. 34%, p = 0.003).
During the hospital stay, 26 patients (23%) in group A and 5 (8%) in
group B died (p = 0.01). Cardiogenic shock accounted for 74% of deaths.
Cardiogenic shock developed in 30 patients (26%) in group A and in 4
(6%) in group B (p = 0.001). The absence of collateral circulation
appeared to be an independent predictor of in-hospital death (odds ratio
3.4, 95% confidence interval 1.2 to 9.6, p = 0.02) and cardiogenic shock
(odds ratio 5.6, 95% confidence interval 1.9 to 17, p = 0.002).
CONCLUSIONS: Preexistent collateral circulation decreases in-hospital
death from anterior AMI by reducing the incidence of cardiogenic shock.
TITLE: Coronary thrombi increase PTCA risk. Angioscopy as a clinical
SOURCE: Circulation (United States), Jan 15 1996, 93(2) p253-8
White CJ; Ramee SR; Collins TJ; Escobar AE; Karsan A; Shaw D; Jain SP;
Bass TA; Heuser RR; Teirstein PS; Bonan R; Walter PD; Smalling RW
BACKGROUND: The presence of angiographically identified intracoronary
thrombus has been variably associated with complications after coronary
angioplasty. Angiography has been shown to be less sensitive than
angioscopy for detecting subtle details of intracoronary morphology,
such as intracoronary thrombi. The clinical importance of thrombi
detectable by angioscopy but not by angiography is not known. METHODS
AND RESULTS: Percutaneous coronary angioscopy was performed in 122
patients undergoing conventional coronary balloon angioplasty (PTCA) at
six medical centers. Unstable angina was present in 95 patients (78%)
and stable angina in 27 (22%). Therapy was not guided by angioscopic
findings, and no patient received thrombolytic therapy as an adjunct to
angioplasty. Coronary thrombi were identified in 74 target lesions (61%)
by angioscopy versus only 24 (20%) by angiography. A major in-hospital
complication (death, myocardial infarction, or emergency bypass surgery)
occurred in 10 of 74 patients (14%) with angioscopic
intracoronary thrombus, compared with only 1 of 48 patients (2%) without
thrombi (P = .03). In-hospital recurrent ischemia (recurrent angina,
repeat PTCA, or abrupt occlusion) occurred in 19 of 74 patients (26%)
with angioscopic intracoronary thrombi versus only 5 of 48 (10%) without
thrombi (P = .03). Relative risk analysis demonstrated that angioscopic
thrombus was strongly associated with adverse outcomes (either a major
complication or a recurrent ischemic event) after PTCA (relative risk,
3.11; 95% CI, 1.28 to 7.60; P = .01) and that angiographic thrombi were
not associated with these complications (relative risk, 0.85; 95% CI,
0.36 to 2.00; P = .91). CONCLUSIONS: The presence of intracoronary
thrombus associated with coronary stenoses is significantly
underestimated by angiography. Angioscopic intracoronary thrombi, the
majority of which were not detected by angiography, are associated with
an increased incidence of adverse outcomes after coronary angioplasty.
TITLE: Clinical and angiographic implications of coronary stenting in
SOURCE: J Am Coll Cardiol (United States), Mar 15 1997, 29(4) p725-33
Alfonso F; Rodriguez P; Phillips P; Goicolea J; Hernandez R;
Perez-Vizcayno MJ; Fernandez-Ortiz A; Segovia J; Banuelos C; Aragoncillo
P; Macaya C
OBJECTIVES: This study sought to determine the results of coronary
stenting in thrombus-laden lesions. BACKGROUND: The angiographic
evidence of intracoronary thrombus has classically been considered a
formal contraindication to stent implantation. However, with increasing
use of stenting, the indications for this technique have widened to
include treatment of patients who have an acute coronary syndrome or
lesions with adverse anatomic features. METHODS: We studied 86
consecutive patients (mean age +/- SD 61 +/- 11 years, 14 women)
undergoing coronary stenting of a thrombus-containing lesion; the
procedure was performed electively in 39% and after angioplasty failure
in 61%. Sixty-four patients (75%) were treated for unstable angina, and
19 (22%) underwent the procedure during an acute myocardial infarction.
A specific protocol that included clinical and late angiographic
follow-up was used. RESULTS: Angiographic success was obtained in 83
patients (96%). Five patients (6%) died during the hospital stay despite
angiographic success; four of these had cardiogenic shock, and one (1%)
had subacute stent thrombosis. Non-Q wave myocardial infarction
developed in five additional patients (6%), and four of these five had
data consistent with distal embolization. Of the 78 patients discharged
with angiographic success, 67 (86%) were event-free and clinically
improved at last follow-up visit (12 +/- 11 months). During the
follow-up period, eight patients required repeat angioplasty, one
patient required heart transplantation, and two patients died.
Quantitative angiography demonstrated excellent angiographic results
after stenting (minimal lumen diameter 0.31 +/- 0.4 vs. 2.77 +/- 0.6
mm). Late angiographic follow-up (5.5 +/- 1 months) was obtained in 50
patients with 54 lesions (93% of eligible), revealing a minimal lumen
diameter of 2.0 +/- 1 mm and restenosis (lumen narrowing 50%) in 18
lesions (33%). CONCLUSIONS: Coronary stenting constitutes an effective
therapeutic strategy for patients with thrombus-containing lesions,
either after failure of initial angioplasty or electively as the primary
procedure. Coronary stenting in this adverse anatomic setting results in
a high degree of angiographic success, a low incidence of subacute
thrombosis and an acceptable restenosis rate.
TITLE: Evidence for prevention of death and myocardial infarction with
platelet membrane glycoprotein IIb/IIIa receptor blockade by abciximab
(c7E3 Fab) among patients with unstable angina undergoing percutaneous
coronary revascularization. EPIC Investigators.Evaluation of 7E3 in
Preventing Ischemic Complications.
SOURCE: J Am Coll Cardiol (United States), Jul 1997, 30(1) p149-56
Lincoff AM; Califf RM; Anderson KM; Weisman HF; Aguirre FV; Kleiman NS;
Harrington RA; Topol EJ
OBJECTIVES: We sought to evaluate whether patients with unstable angina
undergoing coronary intervention derive particular clinical benefit from
potent platelet inhibition. BACKGROUND: Plaque rupture and platelet
aggregation are pathogenetic processes common to unstable angina and
ischemic complications of percutaneous coronary intervention. METHODS:
Of the 2,099 patients undergoing a coronary intervention in the
Evaluation of 7E3 in Preventing Ischemic Complications (EPIC) trial, 489
were enrolled with the diagnosis of unstable angina and randomized to
receive placebo, an abciximab (c7E3) bolus immediately before the
intervention or an abciximab bolus followed by a 12-h infusion. The
primary end point was a composite of death, myocardial infarction (MI)
or urgent repeat revascularization within 30 days of randomization. The
occurrence of death, MI or any revascularization within 6 months was
also assessed. RESULTS: Compared with placebo, the bolus and infusion of
abciximab resulted in a 62% reduction in the rate of the primary end
point (12.8% vs. 4.8%, p = 0.012) among patients with unstable angina,
due primarily to a reduction in the incidences of death (3.2% vs. 1.2%,
p = 0.164) and MI (9% vs. 1.8%, p = 0.004). By 6 months, cumulative
death and MI were further reduced by abciximab (6.6% vs. 1.8%, p = 0.018
and 11.1% vs. 2.4%, p = 0.002, respectively). The magnitude of the risk
reduction with abciximab was greater among the patients with unstable
angina than among other patients in the EPIC trial without unstable
angina for the end points of death (interaction: p = 0.008 at 30 days, p
= 0.002 at 6 months) and MI (interaction: p = 0.004 at 30 days, p =
0.003 at 6 months). CONCLUSIONS: The syndrome of unstable angina
identifies patients who will experience particularly marked reductions
in the risk of death and MI with abciximab during coronary intervention.
TITLE: Angioplasty of complex lesions in ischemic rest angina: results
of the Thrombolysis and Angioplasty in Unstable Angina (TAUSA) trial.
SOURCE: J Am Coll Cardiol (United States), Oct 1995, 26(4) p961-6
Mehran R; Ambrose JA; Bongu RM; Almeida OD; Israel DH; Torre S; Sharma
SK; Ratner DE
OBJECTIVES. This study sought to analyze the role of complex lesion
morphology on the acute results of angioplasty. BACKGROUND. Acute
complications of angioplasty are higher in unstable than in stable
angina. The unstable culprit lesion is usually complex, indicative of
plaque disruption and thrombus formation. Previous nonrandomized studies
have shown that the presence of intracoronary thombus increases
morbidity after coronary angioplasty. The role of complex morphology in
coronary angioplasty outcome was studied in a prespecified subgroup
analysis of a large multicenter coronary angioplasty trial. METHODS. The
results of coronary angioplasty from the Thrombolysis and Angioplasty in
Unstable Angina (TAUSA) trial were analyzed. This large trial randomized
469 patients in double-blinded manner to receive either intracoronary
urokinase or placebo during coronary angioplasty of the culprit lesion
in ischemic rest angina with or without recent infarction. The study
presented here analyzes in detail the results of coronary angioplasty in
complex versus simple lesions in the urokinase and placebo groups.
Complex lesions were defined before angioplasty by a core laboratory as
having one or more of the following: irregular borders, overhanging
edges, ulcerations or intraluminal filling defects proximal or distal to
the lesion. RESULTS. Of the 469 patients, 458 had identifiable culprit
lesions, of which 245 were complex and 213 were simple. Complex lesions
were associated with a higher abrupt closure rate than simple lesions
(10.6% vs. 3.3%, respectively, p 0.003). Patients with complex lesions
also had higher recurrent in-hospital angina (p 0.02) and emergent
bypass surgery (p 0.02). Further analysis of complex lesions revealed
that abrupt closure was particularly high in the urokinase group (15.0%
vs 5.9% for the placebo group, p 0.03), and most abrupt closures were
thrombotic. Composite clinical end points were also significantly higher
with complex lesions and urokinase. In the placebo group, complex
lesions had a higher abrupt closure rate as well as postcoronary
angioplasty filling defects, but clinical end points were not
significantly different. CONCLUSIONS. Complex lesions before coronary
angioplasty increase acute complication rates after coronary
angioplasty. Urokinase as administered in the TAUSA trial had
significant adverse effects, especially in complex lesions. However,
even in the placebo arm, complex lesions were associated with higher
complication rates than simple lesions. Newer antithrombotic measures
that particularly target the platelet may eventually decrease complication
rates in these lesions.
TITLE: Increased risk of non-Q wave myocardial infarction after
directional atherectomy is platelet dependent: evidence from the EPIC
trial. Evaluation of c7E3 for the Prevention of Ischemic Complications.
SOURCE: J Am Coll Cardiol (United States), Oct 1996, 28(4) p849-55
Lefkovits J; Blankenship JC; Anderson KM; Stoner GL; Talley JD; Worley
SJ; Weisman HF; Califf RM; Topol EJ
OBJECTIVES: We sought to determine the effects of platelet glycoprotein
IIb/IIIa receptor blockade on adverse outcomes, especially non-Q wave
myocardial infarction, in patients undergoing directional atherectomy in
the Evaluation of c7E3 for the Prevention of Ischemic Complications
(EPIC) trial. BACKGROUND: Randomized trials comparing directional
atherectomy with percutaneous transluminal coronary angioplasty (PTCA)
have demonstrated modest benefits favoring atherectomy but at a cost of
increased acute ischemic complications, notably non-Q wave myocardial
infarction. The mechanism for this excess risk is unknown. METHODS: Of
2,038 high risk patients undergoing coronary intervention in the EPIC
trial, directional atherectomy was performed in 197 (10%). Patients
randomly received the chimeric glycoprotein IIb/IIIa antibody 7E3
(c7E3), as a bolus or a bolus and 12-h infusion or placebo. Study end
points included death, myocardial infarction, repeat intervention or
bypass surgery. RESULTS: Patients undergoing directional atherectomy had
a lower baseline risk for acute complications but had a higher incidence
of any myocardial infarction (10.7% vs. 6.3%, p = 0.021) and non-Q wave
myocardial infarction (9.6% vs. 4.9%, p = 0.006). Bolus and infusion of
c7E3 reduced non-Q wave myocardial infarctions by 71% after atherectomy
(15.4% for placebo vs. 4.5% for bolus and infusion, p = 0.046). Non-Q
wave myocardial infarction rates after PTCA were not affected by c7E3,
although Q wave myocardial infarctions were reduced from 2.6% to 0.8% (p
= 0.017). CONCLUSIONS: The EPIC trial confirmed the increased risk of
non-Q wave myocardial infarction with directional atherectomy use
compared with PTCA. A bolus and 12-h infusion of the glycoprotein
IIb/IIIa receptor inhibitor c7E3 abolished this excess risk. Directional
atherectomy-related non-Q wave myocardial infarction appears to be
platelet aggregation dependent.
TITLE: An overview of the results of the EPIC trial.
SOURCE: Eur Heart J (England), Nov 1995, 16 Suppl L p43-9
Califf RM; Lincoff AM; Tcheng JE; Topol EJ
The Evaluation of 7E3 for the Prevention of Ischaemic Complications
(EPIC) trial assessed the use of abciximab in the treatment of patients
at high risk undergoing percutaneous revascularization procedures.
Abciximab (c7E3) is a chimeric monoclonal antibody targeted to block the
glycoprotein IIb/IIIa receptor on the surface of the platelet; this
receptor is believed to be the final common pathway of platelet
aggregation. Administered at the time of angioplasty or directional
coronary atherectomy, abciximab had a beneficial effect in the
population studied, which included patients considered to be at high
risk from complications of the procedure, based on the presence of acute
or recent myocardial infarction, severe unstable angina or adverse
coronary morphological characteristics. Abciximab reduced the risk of
the primary endpoint at 30 days (death, myocardial infarction, repeat
angioplasty or bypass surgery for recurrent ischaemia, balloon pump or
stent insertion for ischaemia) by 35%: from 12.8% in the placebo group
to 8.3% in patients treated with abciximab bolus and infusion. This
trend was observed as a whole and in each component of the primary
endpoint. At 6 months follow-up, the effect of the treatment was
modestly enhanced beyond 30 days. A variety of substudies have
documented substantial evidence of treatment benefit in patients with
acute myocardial infarction and unstable angina. Non-fatal infarction,
observed as beyond that normally expected in other studies with
directional coronary atherectomy, was not above normal in patients
treated with abciximab, and there was evidence of a treatment benefit in
the elderly, although more information would be helpful in patients over
the age of 70. The substantial site-to-site variability indicates that
standardization of percutaneous revascularization could enhance the
benefit of abciximab, while reducing bleeding complications.
TITLE: Stress echocardiographic results predict risk of reinfarction
early after uncomplicated acute myocardial infarction: large-scale
multicenter study. Echo Persantine International Cooperative (EPIC)
SOURCE: J Am Coll Cardiol (United States), Oct 1995, 26(4) p908-13
Picano E; Pingitore A; Sicari R; Minardi G; Gandolfo N; Seveso G;
Chiarella F; Bolognese L; Chiaranda G; Sclavo MG; et al
OBJECTIVES. This study sought to assess the value of dipyridamole
echocardiography in predicting reinfarction in patients evaluated early
after uncomplicated acute myocardial infarction. BACKGROUND. The
identification of future nonfatal reinfarction seems an elusive target
for physiologic testing. However, a large sample population is needed to
detect minor differences in phenomena with a low event rate. METHODS. We
assessed the value of dipyridamole echocardiography in predicting
reinfarction in 1,080 patients (mean [+/- SD] age 56 +/- 9 years; 926
men, 154 women) evaluated early (10 +/- 5 days) after uncomplicated
acute myocardial infarction and followed up for 14 +/- 10 months.
RESULTS. Submaximal studies due to limiting side effects occurred in 14
patients (1.3%); these test results were included in the analysis.
Results of dipyridamole echocardiography were positive in 475 patients
(44%). During follow-up, there were 50 reinfarctions: 45 nonfatal, 5
fatal (followed by cardiac death or = 4 days after reinfarction).
Reinfarction (either nonfatal or fatal) occurred in 30 patients with
positive and 20 with negative results (6.3% vs. 3.3%, p 0.01). Nonfatal
reinfarction occurred in 25 patients with positive and 20 with negative
results (5% vs. 3.3%, p 0.05). Reinfarction was fatal in 5 of 30
patients with positive and in none of 20 with negative results (16.6%
vs. 0%, p = 0.07). The relative risk of reinfarction was 1.9.
CONCLUSIONS. Dipyridamole echocardiographic positivity identifies
patients evaluated early after uncomplicated acute myocardial infarction
at higher risk of reinfarction, especially fatal reinfarction.
TITLE: Platelet glycoprotein IIb/IIIa receptor blockade and low-dose
heparin during percutaneous coronary revascularization. The EPILOG
SOURCE: N Engl J Med (United States), Jun 12 1997, 336(24) p1689-96
BACKGROUND: Blockade of the platelet glycoprotein IIb/IIIa receptor with
abciximab (a monoclonal-antibody Fab fragment directed against the
receptor) has been shown to diminish ischemic complications among
patients undergoing high-risk coronary angioplasty or directional
atherectomy but increases bleeding complications. The widespread
applicability of this treatment is unknown, particularly in view of the
observed risk of hemorrhage. METHODS: In a prospective, double-blind
trial, we randomly assigned patients undergoing urgent or elective
percutaneous coronary revascularization at 69 centers to receive
abciximab with standard-dose, weight-adjusted heparin (initial bolus of
100 U per kilogram of body weight); abciximab with low-dose,
weight-adjusted heparin (initial bolus of 70 U per kilogram); or placebo
with standard-dose, weight-adjusted heparin. The primary efficacy end
point was death from any cause, myocardial infarction, or urgent
revascularization within 30 days of randomization. RESULTS: The trial
was terminated at the first interim analysis, with 2792 of the planned
4800 patients enrolled. At 30 days, the composite event rate was 11.7
percent in the group assigned to placebo with standard-dose heparin; 5.2
percent in the group assigned to abciximab with low-dose heparin (hazard
ratio, 0.43; 95 percent confidence interval, 0.30 to 0.60; P 0.001); and
5.4 percent in the group assigned to abciximab with standard-dose
heparin (hazard ratio, 0.45; 95 percent confidence interval, 0.32 to
0.63; P 0.001). There were no significant differences among the groups
in the risk of major bleeding, although minor bleeding was more frequent
among patients receiving abciximab with standard-dose heparin.
CONCLUSIONS: Inhibition of the platelet glycoprotein IIb/IIIa receptor
with abciximab, together with low-dose, weight-adjusted heparin,
markedly reduces the risk of acute ischemic complications in patients
undergoing percutaneous coronary revascularization, without increasing
the risk of hemorrhage.
TITLE: Randomised placebo-controlled trial of abciximab before and
during coronary intervention in refractory unstable angina: the CAPTURE
SOURCE: Lancet (England), May 17 1997, 349(9063) p1429-35
BACKGROUND: Platelet aggregation is a dominant feature in the
pathophysiology of unstable angina. Percutaneous transluminal coronary
angioplasty (PTCA) in patients with this disorder carries an increased
risk of thrombotic complications. Abciximab (c7E3) blocks the platelet
glycoprotein IIb/IIIa receptor, thus preventing platelet adhesion and
aggregation. The CAPTURE study was a randomised placebo-controlled
multicentre trial to assess whether abciximab can improve outcome in
patients with refractory unstable angina who are undergoing PTCA.
METHODS: The study recruited patients with refractory unstable angina,
defined as recurrent myocardial ischaemia under medical treatment
including heparin and nitrates. Predefined stopping rules were met at a
planned interim analysis of data for 1050 patients, and recruitment was
stopped. Data for 1265 patients (of 1400 scheduled) are presented here.
After angiography, patients received a randomly assigned infusion of
abciximab or placebo for 18-24 h before PTCA, continuing until 1 h
afterwards. The primary endpoint was the occurrence within 30 days after
PTCA of death (any cause), myocardial infarction, or urgent intervention
for recurrent ischaemia. Analyses were by intention to treat. FINDINGS:
By 30 days, the primary endpoint had occurred in 71 (11.3%) of 630
patients who received abciximab compared with 101 (15.9%) of 635 placebo
recipients (p = 0.012). The rate of myocardial infarction was lower in
the abciximab than in the placebo group before PTCA (four [0.6%] vs 13
[2.1%], p = 0.029) and during PTCA (16 [2.6%] vs 34 [5.5%], p = 0.009).
Major bleeding was infrequent, but occurred more often with abciximab
than with placebo (24 [3.8%] vs 12 [1.9%], p = 0.043). At 6-month
follow-up, death, myocardial infarction, or repeat intervention had
occurred in 193 patients in each group. INTERPRETATION: In patients with
refractory unstable angina, treatment with abciximab substantially
reduces the rate of thrombotic complications, in particular myocardial
infarction, before, during, and after PTCA. There was no evidence that
this regimen influenced the rate of myocardial infarction after the
first few days, or the need for subsequent reintervention.
TITLE: Intracoronary morphology of culprit lesions after reperfusion in
acute myocardial infarction: serial angioscopic observations.
SOURCE: J Am Coll Cardiol (United States), Mar 1 1996, 27(3) p606-10
Ueda Y; Asakura M; Hirayama A; Komamura K; Hori M; Komada K
OBJECTIVE: This study sought to elucidate the morphologic and pathologic
characteristics of culprit lesions in patients with acute myocardial
infarction. BACKGROUND: The pathogenic mechanisms of acute myocardial
infarction have been discussed on the basis of postmortem histologic
examinations. Disruption of lipid-rich plaques is thought to render them
thrombogenic. However, the details of coronary morphology have not been
elucidated in survivors of myocardial infarction. The quality of
angioscopic images has been greatly improved, and clear visualization of
the intracoronary milieu can now be obtained. METHODS: Eleven patients
with acute myocardial infarction and angiographic demonstration of the
culprit lesion were entered into the study. Angioscopic observations
were made immediately after reperfusion and at 1-month follow-up.
RESULTS: Angioscopic observations were successfully performed in 10
patients immediately after reperfusion and in 10 at 33 +/- 26 (mean +/-
SD) days of follow-up. Immediately after reperfusion, red thrombus,
white thrombus, yellow plaques and intimal flaps were recognized in 30%
(95% confidence interval [CI] 25.7 to 35.7), 100%, 100% and 50% (95% CI
45.0 to 55.0) of patients, respectively. At follow-up, these were
recognized in 10% (95% CI 6.6 to 16.4), 60% (95% CI 54.6 to 64.7), 100%
and 40% (95% CI 35.3 to 45.4) of patients, respectively. CONCLUSIONS:
The thrombus in acute myocardial infarction was always recognized over
the yellow plaques. The thrombus formed directly over the plaque was
mainly white. Red thrombus might be formed after the blood flow was
obstructed by the white thrombus. At approximately 1 month, yellow
plaques remained in all patients, and 50% still had adherent white
TITLE: A randomized trial of low osmolar ionic versus nonionic contrast
media in patients with myocardial infarction or unstable angina
undergoing percutaneous transluminal coronary angioplasty.
SOURCE: J Am Coll Cardiol (United States), May 1996, 27(6) p1381-6
Grines CL; Schreiber TL; Savas V; Jones DE; Zidar FJ; Gangadharan V;
Brodsky M; Levin R; Safian R; Puchrowicz-Ochocki S; Castellani MD;
OBJECTIVES: The purpose of this study was to determine prospectively
whether the differences in anticoagulant and antiplatelet effects of
ionic and nonionic contrast media after angiographic or clinical
outcomes in patients with unstable ischemic syndromes undergoing
percutaneous transluminal coronary angioplasty. BACKGROUND: The
interaction of platelets and thrombin with the endothelium of injured
vessels contributes to thrombosis and restenosis after coronary
angioplasty. Case reports and retrospective observations have reported
an increased risk of thrombosis with the use of nonionic contrast media.
METHODS: A total of 211 patients with acute myocardial infarction or
unstable angina undergoing coronary angioplasty were randomized to
receive nonionic or ionic low osmolar contrast media. Coronary
angiograms were assessed by a technician blinded to the study contrast
media, and clinical events were monitored by an independent nurse for 1
month. RESULTS: Patients receiving the ionic media were significantly
less likely to experience decreased blood flow during the procedure
(8.1% vs. 17.8%, p = 0.04). After the angioplasty, residual stenosis,
vessel patency, the incidence of moderate to large thrombi and use of
adjunctive thrombolytic therapy were similar between the two groups.
However, patients receiving ionic media had fewer recurrent ischemic
events requiring repeat catheterization (3.0% vs. 11.4%, p = 0.02) and
repeat angioplasty during the initial hospital stay (1.0% vs. 5.8%, p =
0.06). One month after angioplasty, patients receiving ionic contrast
media reported significantly fewer symptoms of any angina (8.5 vs.
20.0%, p = 0.04) or of angina at rest (1.4% vs. 11.8%, p = 0.01) and a
reduced need for subsequent bypass surgery (0% vs. 5.9%, p = 0.04),
compared with patients receiving the nonionic media. CONCLUSIONS: These
findings demonstrate that in patients with unstable ischemic syndromes
undergoing coronary angioplasty, the use of ionic low osmolar contrast
media reduces the risk of ischemic complications acutely and at 1 month
after the procedure. Therefore, low osmolar ionic contrast media should
be strongly considered when performing interventions in patients with
unstable angina or myocardial infarction.
TITLE: Management of unstable angina: the role of noninvasive risk
SOURCE: J Nucl Cardiol (United States), Mar-Apr 1997, 4(2 Pt 2) pS164-8
Many cardiologists rely primarily on catheterization to evaluate, and
revascularization to treat, patients with unstable angina. In this era
of managed care and cost containment, it is useful to determine whether
some patients with unstable angina might benefit sufficiently from
noninvasive testing and medical therapies. Several studies provide
evidence that myocardial perfusion imaging is valuable for evaluating
cardiac risk and thus determining the best candidates for medical
treatment. Comparative studies indicate that myocardial perfusion
imaging is superior to stress electrocardiography for assessing risk in
patients with unstable angina.
TITLE: Prognostic value of predischarge dipyridamole technetium 99m
sestamibi myocardial tomography in medically treated patients with
SOURCE: Am Heart J (United States), Oct 1995, 130(4) p734-40
Stratmann HG; Tamesis BR; Younis LT; Wittry MD; Amato M; Miller DD
Recently developed unstable angina clinical practice guidelines have
recommended risk stratification with dipyridamole thallium-201
myocardial imaging in patients at "intermediate" pretest
clinical risk who cannot exercise maximally. The prognostic value of
predischarge dipyridamole technetium 99m sestamibi (MIBI) tomography has
not been assessed in this clinical setting. To this end, 128 medically
treated patients with unstable angina at intermediate pretest clinical
risk underwent follow-up for 16 +/- 11 (mean +/- SD) months after
predischarge intravenous dipyridamole MIBI tomography. An abnormal MIBI
scan result was present in 99 patients (77%), of whom 47 had one or more
reversible and 76 had one or more fixed perfusion defects. Cardiac
events occurred in 68 (53%) patients after dipyridamole testing:
recurrent unstable angina (n = 36), nonfatal acute myocardial infarction
(n = 6), or death (n = 26). A cardiac event occurred in 10% of patients
with normal MIBI tomography results compared with 69% of those with
abnormal results (p 0.01). Event rates associated with specific
perfusion defects were similar (reversible = 68%; fixed = 71%) and were
greater than rates in patients without defects (both p 0.05). Clinical
variables associated with increased risk of cardiac events by univariate
analysis included a history of congestive heart failure, prior
myocardial infarction, and diabetes mellitus (all p 0.05). Independent
multivariable predictors (Cox proportional hazards model) of any cardiac
event were an abnormal result of MIBI scan (relative risk [RR] = 4.3,
95% confidence interval [CI] 1.5 to 12.0) and a reversible (RR = 1.8,
95% CI 1.1 to 2.9) or a fixed perfusion defect (RR = 2.9, 95% CI 1.6 to
5.4).(ABSTRACT TRUNCATED AT 250 WORDS).
TITLE: Rapid angiographic progression of coronary artery disease in
patients with angina pectoris. The role of complex stenosis morphology.
SOURCE: Circulation (United States), Oct 15 1995, 92(8) p2058-65
Kaski JC; Chester MR; Chen L; Katritsis D
BACKGROUND: Rapid disease progression commonly underlies acute coronary
events, and "complex" stenosis morphology may play a role in
this phenomenon. METHODS AND RESULTS: We studied the role of complex
stenosis morphology in rapid disease progression in 94 consecutive
patients awaiting routine coronary angioplasty. Coronary arteriography
was repeated at 8 +/- 3 months' follow-up, immediately preceding
angioplasty (68 patients) or after an acute coronary event (26
patients). Disease progression of 217 stenoses, of which 79 (36%) were
"complex" and 138 (64%) were "smooth," was assessed
by computerized angiography. At presentation, 63 patients had stable
angina pectoris and 31 had unstable angina that settled rapidly with
medical therapy. At follow-up, 23 patients (24%) had progression of
preexisting stenoses and 71 (76%) had no progression. Patients with
progression were younger (55 +/- 12 years) than those without (58 +/- 9
years) but did not differ with regard to risk factors, previous
myocardial infarction, or severity and extent of coronary disease.
Twenty-three lesions (11%) progressed, 15 to total occlusion (11 complex
and 4 smooth; 65%). Progression occurred in 17 of the 79 complex
stenoses (22%) and in 6 of the 138 smooth lesions (4%) (P = .002). Mean
stenosis diameter reduction was also significantly greater in complex
than in smooth lesions (11.6% versus 3.9% change; P .001). Acute
coronary events occurred in 57% of patients with progression compared
with 18% of those without progression (P .001) and were more frequent in
patients who presented with unstable angina (P = .002). CONCLUSIONS:
Rapid stenosis progression is not uncommon, and complex stenoses are at
risk more than smooth lesions.
TITLE: Prognostic evaluation of patients after myocardial infarction:
incremental value of sestamibi single-photon emission computed
tomography and echocardiography.
SOURCE: J Nucl Cardiol (United States), Mar-Apr 1997, 4(2 Pt 1) p117-24
Zanco P; Zampiero A; Favero A; Borsato N; Chierichetti F; Rubello D;
BACKGROUND: This study compares the prognostic value of 99mTc-labeled
methoxyisobutyl isonitrile (MIBI) single-photon emission computed
tomographic (SPECT) imaging, echocardiography, and other clinical and
laboratory prognostic factors in the long-term risk stratification of
patients with stable uncomplicated infarcts. METHODS AND RESULTS:
Ninety-one consecutive patients affected by a first myocardial
infarction without serious complications were enrolled. After at least 3
months from the infarction, they were submitted to stress-rest MIBI
SPECT and rest echocardiography. Eighty-six patients completed a
follow-up of at least 4 years (range 48 to 72 months; mean 55 months).
By univariate (log-rank test) and multivariate analysis (Cox
proportional hazards model), the main clinical, electrocardiographic,
scintigraphic, and echocardiographic findings were evaluated and
correlated statistically with the incidence of ensuing cardiac events.
Twenty-five patients had cardiac events during the follow-up (four
cardiac deaths, four myocardial infarctions, and 17 cases of unstable
angina). At the multivariate analysis, the presence of reversible
defects on MIBI SPECT (p = 0.008 and relative risk [RR] = 7.09), the
wall motion score index, and the ejection fraction at echocardiography
(respectively, p = 0.010, RR = 3.67, p = 0.036, and RR = 3.12), and
stress angina (p = 0.007 and RR = 3.40) were significant and independent
prognostic factors. CONCLUSIONS: In our long-term follow-up, MIBI SPECT
and echocardiography appeared to be significant and independent
prognostic tools in the risk stratification of patients with stable,
uncomplicated infarcts, furnishing complementary information. The
reversibility of MIBI defects appeared the best indicator for a bad
TITLE: Prognostic value of exercise 201Tl tomography in patients treated
with thrombolytic therapy during acute myocardial infarction.
SOURCE: Circulation (United States), Dec 1 1996, 94(11) p2735-42
Dakik HA; Mahmarian JJ; Kimball KT; Koutelou MG; Medrano R; Verani MS
BACKGROUND: Although myocardial perfusion scintigraphy is of proven
value in the risk stratification of patients with a recent myocardial
infarction who receive conventional therapy, its value in patients
undergoing thrombolytic therapy remains controversial. METHODS AND
RESULTS: Seventy-one patients who received thrombolytic therapy for
acute myocardial infarction had exercise 201Tl tomography and coronary
angiography before hospital discharge. Eleven (15%) of 71 patients had
ischemic ST-segment depression during exercise, whereas 27 patients
(38%) had scintigraphic ischemia. Twenty-five (37%) of 68 patients had a
cardiac event consisting of either death (n = 2), recurrent myocardial
infarction (n = 5), congestive heart failure (n = 7), or unstable angina
(n = 11) during a follow-up of 26 +/- 18 months. Univariate predictors
of cardiac events were as follows: Killip class (P = .04); left
ventricular ejection fraction (P .0005); total (P = .002) and ischemic
(P .0005) perfusion defect size; percent thallium lung uptake (P =
.001); presence of infarct-zone redistribution (P = .02); and
multivessel coronary artery disease (P = .01). By multivariate analysis,
the significant joint predictors of risk were ejection fraction (P
.0005) and ischemic perfusion defect size (P = .005). The combination of
ejection fraction and thallium tomography added significant incremental
prognostic information to the clinical data, whereas angiography did not
further improve a model that included clinical, ejection fraction, and
tomographic variables. CONCLUSIONS: Quantitative exercise 201Tl
tomography provides important incremental, long-term prognostic
information in patients receiving thrombolytic therapy for acute
TRIAL: results are supported by many other studies
and Overuse of Angiography and Revascularization for Acute Coronary
Syndromes (with references at the end)
England Journal of Medicine -- June 18, 1998 -- Volume 338, Number 25
past two decades, clinical and pathological studies have examined the
pathophysiology of the acute coronary syndromes, unstable angina, and
non-Q-wave and Q-wave myocardial infarction. In these conditions,
rupture of atherosclerotic plaques leads to varying amounts of platelet
adhesion and aggregation, vasoconstriction, and the formation of
partially or totally occlusive thrombus. Although the inhibition of
platelet aggregation and thrombus formation and the restoration of
antegrade flow in occluded coronary arteries improve survival and reduce
the incidence of recurrent ischemia and infarction, residual
coronary-artery stenosis may cause ischemia, infarction, or even death.
As a result, there has been considerable interest in the routine use of
coronary angiography and percutaneous revascularization in patients with
these syndromes, in the hope of reducing the risk of adverse events.
publication of the results of the Veterans Affairs Non-Q-Wave Infarction
Strategies in Hospital (VANQWISH) Trial in this issue of the Journal (1)
brings to four the number of large prospective, randomized studies
comparing "aggressive" and "conservative" management
of acute coronary syndromes. Together, these trials have studied more
than 6400 patients with unstable angina, (2,3) non-Q-wave infarction,
(1,2,3) or Q-wave infarction treated with thrombolytic therapy (4,5,6)
who have been assigned to routine aggressive management or to a more
conservative strategy, in which angiography and revascularization are
performed only in patients with spontaneous or provokable myocardial
ischemia (i.e., ischemia-guided therapy). With remarkable clarity and
consistency, all four studies show that routine angiography and
revascularization do not reduce the incidence of nonfatal reinfarction
or death as compared with the more conservative, ischemia-guided
approach. In fact, in the VANQWISH study of patients with non-Q-wave
infarction, (1) the aggressive strategy (which these investigators call
"invasive") was associated with increased mortality during
hospitalization, at one month, and at one year.
all four trials (1,2,3,4,5,6) found that the incidence of adverse events
was similar (or greater) in patients whose acute coronary syndromes were
managed aggressively than in those assigned to conservative management,
an aggressive approach continues to be chosen by most physicians in the
United States, whereas a conservative strategy is more likely to be
followed in Canada and Europe. In the Global Utilization of
Streptokinase and Tissue Plasminogen Activator for Occluded Coronary
Arteries (GUSTO) trial, (7) which was performed in the United States and
abroad, four thrombolytic regimens were compared in patients with Q-wave
infarction. After each patient had received one of the four thrombolytic
regimens, treatment was determined by his or her own physician.
the patients enrolled in the United States were more likely than their
Canadian counterparts to undergo coronary angiography (68 percent vs. 35
percent, respectively) and subsequent revascularization (31 percent vs.
12 percent), the incidence of reinfarction and death during more than
three years of follow-up was similar. (8) The chief predictors of the
decision by U.S. physicians to use coronary angiography were a
relatively young age of the patient and the availability of a
catheterization facility. Furthermore, there was marked regional
variation within the United States in the rates of use of angiography
and revascularization, (9) which was not explained by differences in the
characteristics of the patients or the incidence of complications of
myocardial infarction. A strong relation was noted between the
availability of angiography in a geographic area and the likelihood that
aggressive management would be chosen. However, the increased use of
invasive procedures did not reduce the incidence of recurrent infarction
coronary angiography and revascularization often performed in patients
with acute coronary syndromes in the United States, even without an
obvious indication? Several factors may be responsible. First, in an era
in which invasive cardiac procedures are manifestations of
high-technology, resource-intensive medical care, many patients and
their family members expect and insist on aggressive management. The
term "conservative management" may project the impression (to
physicians and patients alike) of obsolescence, inadequacy, and
inferiority rather than of thoughtful reflection and the application of
scientifically based, ischemia-guided therapy. In the event of an
adverse outcome, the patient and his or her family may be more
understanding and forgiving if an aggressive approach was pursued (i.e.,
if "everything possible was done"), even if such an approach
contributes, directly or indirectly, to the adverse outcome. In the
GUSTO trial, (7) physicians in the United States more often reported
that requests by the patient or family members as well as concern about
liability influenced them to pursue aggressive management than did their
Canadian counterparts. (8)
some physicians in the United States express skepticism about the
applicability of the results of the aforementioned trials to their
patients. In the three randomized comparisons of aggressive and
conservative management strategies conducted in the United States,
(1,2,4) 70 to 80 percent of the patients initially assigned to
conservative management nonetheless underwent coronary angiography
during or shortly after their index hospitalization (9,10); in many
cases, angiography was recommended without a clear indication. Of the
physicians in the United States who participated in the GUSTO trial who
were surveyed, (8) 54 percent said they routinely recommended coronary
angiography for survivors of uncomplicated myocardial infarction, 71
percent did so for those receiving thrombolytic therapy, and 93 percent
did so for survivors of infarction who were less than 45 years old, even
though these groups of patients are at low risk for subsequent
complications regardless of the manner in which they are treated. In
Europe and Canada, (8,11) in contrast, patients who received
thrombolytic therapy and were assigned to conservative management
underwent angiography and revascularization one third to one half as
often as their U.S. counterparts, yet their outcome was similar, and
routine aggressive management offered no substantial benefit.
studies that substantiate preconceived notions are likely to be embraced
and their recommendations followed, whereas those that do not are often
ignored. For example, primary angioplasty for acute myocardial
infarction is widely used and enthusiastically advocated, yet direct
comparisons with thrombolytic therapy in relatively small numbers of
patients showed, at best, only a small benefit of angioplasty, and
larger studies showed none. (12) Many physicians in the United States,
even today, continue to believe that all patients with acute coronary
syndromes are best treated with prompt coronary angiography and
revascularization, despite the absence of scientific support for such an
as compared with Canada and Europe, the United States has an abundance
of facilities for prompt angiography and revascularization, physicians
trained to perform these procedures, and monetary remuneration to the
facilities and physicians. The combination of these factors encourages
the use of angiography and revascularization without a clear indication.
Physicians who work in hospitals with catheterization facilities are
more likely to recommend coronary angiography than those without easy
access to such a facility. (9,10,11) Cardiologists are more likely to
recommend angiography than internists, and cardiologists who perform
angiography are even more likely than their colleagues who do not
perform the procedure to recommend it. (8,10,13)
present, particularly in the United States, a substantial number of
patients with acute coronary syndromes undergo coronary angiography and
revascularization without a clear indication. Which patients with
unstable angina or myocardial infarction should undergo angiography?
First, those who have spontaneous or provokable ischemia despite
reasonable medical therapy should undergo invasive evaluation and
revascularization. For these patients, angiography and revascularization
are clearly indicated and beneficial. Second, symptomatic patients or
those with evidence from noninvasive tests of left ventricular systolic
dysfunction should undergo angiography, with the goal of identifying
those who would be expected to benefit from subsequent surgical
revascularization. (14) The treatment of patients whose course is
uncomplicated should be guided by the results of the relevant trials,
(1,2,3,4,5,6) such as VANQWISH, (1) rather than physicians' preference
or other, nonmedical incentives.
A. Lange, M.D. L. David Hillis, M.D. University of Texas Southwestern
Dallas, TX 75235-9047
References to the
article of Dr. Lange
WE, O'Rourke RA, Crawford MH, et al. Outcomes in patients with acute
non-Q-wave myocardial infarction randomly assigned to an invasive as
compared with a conservative management strategy. N Engl J Med
Williams DO, Braunwald E, Thompson B, Sharaf BL, Buller CE, Knatterud
GL. Results of percutaneous transluminal coronary angioplasty in
unstable angina and non-Q-wave myocardial infarction: observations from
the TIMI IIIB Trial. Circulation 1996;94:2749-55.
Anderson HV, Cannon CP, Stone PH, et al. One-year results of the
Thrombolysis in Myocardial Infarction (TIMI) IIIB clinical trial: a
randomized comparison of tissue-type plasminogen activator versus
placebo and early invasive versus early conservative strategies in
unstable angina and non-Q wave myocardial infarction. J Am Coll Cardiol
TIMI Study Group. Comparison of invasive and conservative strategies
after treatment with intravenous tissue plasminogen activator in acute
myocardial infarction: results of the Thrombolysis in Myocardial
Infarction (TIMI) phase II trial. N Engl J Med 1989;320:618-27.
ML, Williams DO, Kleiman NS, et al. Two-and three-year results of the
Thrombolysis in Myocardial Infarction (TIMI) Phase II clinical trial. J
Am Coll Cardiol 1993;22:1763-72.
(Should We Intervene Following Thrombolysis?) Trial Study Group. SWIFT
trial of delayed elective intervention v conservative treatment after
thrombolysis with anistreplase in acute myocardial infarction. BMJ
GUSTO Investigators. An international randomized trial comparing four
thrombolytic strategies for acute myocardial infarction. N Engl J Med
L, Granger C, Armstrong PW, Mark DB, Hlatky MA. Differences in the
treatment of myocardial infarction between the United States and Canada:
a survey of physicians in the GUSTO trial. Med Care 1995;33:598-610.
L, Califf RM, Sapp S, et al. Regional variation across the United States
in the management of acute myocardial infarction. N Engl J Med
Pilote L, Miller DP, Califf RM, Rao JS, Weaver WD, Topol EJ.
Determinants of the use of coronary angiography and revascularization
after thrombolysis for acute myocardial infarction. N Engl J Med
de Werf F, Topol EJ, Lee KL, et al. Variations in patient management and
outcomes for acute myocardial infarction in the United States and other
countries: results from the GUSTO trial. JAMA 1995;273:1586-91.
RA, Hillis LD. Should thrombolysis or primary angioplasty be the
treatment of choice for acute myocardial infarction? Thrombolysis -- the
preferred treatment. N Engl J Med 1996;335:1311-2.
NR, Larson EB, Litwin PE, et al. The association between on-site cardiac
catheterization facilities and the use of coronary angiography after
acute myocardial infarction. N Engl J Med 1993;329:546-51.
Alderman EL, Bourassa MG, Cohen LS, et al. Ten-year follow-up of
survival and myocardial infarction in the randomized Coronary Artery
Surgery Study. Circulation 1990;82:1629-46.
of percutaneous transluminal coronary angioplasty in unstable angina and
non-Q-wave myocardial infarction. Observations from the TIMI IIIB Trial.
1996 Dec 1;94(11):2749-2755
DO, Braunwald E, Thompson B, Sharaf BL, Buller CE, Knatterud GL
of Medicine, Rhode Island Hospital, School of Medicine, Brown
University, Providence 02903, USA.
BACKGROUND: This report
describes the results of percutaneous transluminal coronary angioplasty
(PTCA) in the Thrombolysis in Myocardial Ischemia (TIMI) IIIB
Investigation. METHODS AND RESULTS: PTCA was performed before hospital
discharge in 444 of 1473 patients with either unstable angina pectoris
or non-Q-wave myocardial infarction (NQWMI) enrolled in TIMI IIIB.
Angiographic success was observed in 96.1% of patients. For the entire
cohort, the cumulative incidences of death and infarction at 1 year were
2.0% and 8.2%, respectively. The periprocedural incidence of myocardial
infarction was 2.7%; emergency coronary bypass surgery, 1.4%; and death,
0.5%. By 1 year of follow-up, 122 patients (28.0%, Kaplan-Meier) had an
additional revascularization procedure, 75 (61.5%) had PTCA only, 30
(24.6%) had coronary bypass surgery only, and 17 (13.9%) had both
procedures. The results of PTCA were not improved by routine
pretreatment with intravenous tissue plasminogen activator (TPA).
Periprocedural myocardial infarction was more common among patients
receiving TPA than placebo (odds ratio [OR], 2.19; P = .03) and among
those with unstable angina than those with NQWMI (OR, 15.5; P = .007).
No difference in outcome was observed when patients were analyzed
according to age (OR, 1.06; P = .092) or sex (OR, 1.54; P = .51).
Variables predictive of poor outcome were PTCA within the first 24 hours
of enrollment, PTCA site being the left anterior descending coronary
artery, and unsuccessful angiography. CONCLUSIONS: In TIMI IIIB, PTCA
was performed for patients with unstable angina and NQWMI with a very
high rate of angiographic success and a low incidence of complications.
By 1 year, repeat revascularization was performed in 28.0% of patients.
Routine pretreatment with thrombolysis did not enhance outcome.
results of the Thrombolysis in Myocardial Infarction (TIMI) IIIB
clinical trial. A randomized comparison of tissue-type plasminogen
activator versus placebo and early invasive versus early conservative
strategies in unstable angina and non-Q wave myocardial infarction.
J Am Coll
Cardiol 1995 Dec;26(7):1643-1650
HV, Cannon CP, Stone PH, Williams DO, McCabe CH, Knatterud GL, Thompson
B, Willerson JT, Braunwald E
of Texas Health Science Center, Houston 77225, USA.
OBJECTIVES. We report
mortality, infarction, revascularization and repeat hospital admission
events for 1 year after enrollment and randomization in the Thrombolysis
in Myocardial Ischemia (TIMI) IIIB clinical trial. BACKGROUND. The
purpose of this trial was to investigate the role of a thrombolytic
agent added to conventional medical therapies and to compare an early
invasive management strategy to a more conservative early strategy in
patients with unstable angina and non-Q wave myocardial infarction.
METHODS. There were 1,473 patients enrolled, and they received
conventional anti-ischemic medical therapies. They were randomized to
therapy with either tissue-type plasminogen activator (t-PA) or placebo
and also to an early invasive management strategy with coronary
arteriography at 18 to 48 h, followed by revascularization as soon as
possible if appropriate, or, alternatively, to an early conservative
strategy with arteriography and revascularization reserved for failure
of initial therapy to prevent recurrent ischemia. The primary end point
was a composite outcome variable and was assessed at 42 days. Patients
were then managed entirely at the discretion of their treating
physician. Follow-up contacts were made at 1 year. RESULTS. The
incidence of death or nonfatal infarction for the t-PA- and
placebo-treated groups was similar after 1 year (12.4% vs. 10.6%, p =
0.24). The incidence of death or nonfatal infarction was also similar
after 1 year for the early invasive and early conservative strategies
(10.8% vs. 12.2%, p = 0.42). A trial of this size should be able to
detect differences in relative risk for death or infarction > or =
1.81 with a power of 80% at a significance level (alpha) of 0.01.
Revascularization by 1 year was common, but was slightly more common
with the early invasive than the early conservative strategy (64% vs.
58%, p < 0.001). This result was related entirely to a small
difference in angioplasty rates (39% vs. 32%, p < 0.001) inasmuch as
rates of bypass grafting by 1 year were equivalent (30% in each group, p
= 0.50). The high rate of revascularization in both strategies was
accompanied by comparable clinical status at the 1-year follow-up
contact. CONCLUSIONS. In this large study of unstable angina and non-Q
wave myocardial infarction, the incidence of death and nonfatal
infarction or reinfarction was low but not trivial after 1 year (4.3%
mortality, 8.8% nonfatal infarction). An early invasive management
strategy was associated with slightly more coronary angioplasty
procedures but equivalent numbers of bypass surgery procedures than a
more conservative early strategy of catheterization and
revascularization only for signs of recurrent ischemia. The incidence of
death or nonfatal infarction, or both, did not differ after 1 year by
strategy assignment, but fewer patients in the early invasive strategy
group underwent later repeat hospital admission (26% vs. 33%, p <
0.001). Either strategy is appropriate for patient management;
differences in hospital admissions and revascularization procedures,
with their attendant costs, are likely to be minimal.
and three-year results of the Thrombolysis in Myocardial Infarction
(TIMI) Phase II clinical trial.
J Am Coll
Cardiol 1993 Dec;22(7):1763-1772
ML, Williams DO, Kleiman NS, Willerson J, Mueller HS, Desvigne-Nickens
P, Forman SA, Knatterud GL, Braunwald E
Medical Research Institute, Baltimore 21210.
OBJECTIVES. This report
describes the survival and reinfarction rates for 2- and 3-year
follow-up in the Thrombolysis in Myocardial Infarction (TIMI) Phase II
clinical trial. BACKGROUND. Patients enrolled in TIMI II were randomly
assigned to an invasive (1,681 patients) or a conservative (1,658
patients) management strategy to follow receipt of intravenous
recombinant tissue-type plasminogen activator for acute myocardial
infarction. METHODS. Eligibility required presentation within 4h of
onset of symptoms and at least 1-mV ST segment elevation in two
contiguous electrocardiographic leads. The invasive strategy group
underwent cardiac catheterization 18 to 48 h after study entry and, when
appropriate, percutaneous transluminal coronary angioplasty or coronary
artery bypass grafting. In the conservative strategy group these
diagnostic and revascularization procedures were reserved for recurrent
spontaneous ischemia or ischemia on low level exercise at the time of
hospital discharge. RESULTS. Complete 2-year follow-up data are
available for 3,187 patients (95.4%). Cumulative life-table rates of
death or reinfarction were 17.6% for the invasive strategy group and
17.9% for the conservative strategy group (p = NS) and mortality was
8.9% and 8.7% (p = NS), respectively. Complete data are available for
1,959 (90.1%) of the 2,174 patients enrolled for 3 years. Rates of death
or reinfarction were 21.0% for the invasive strategy group with 20.0%
for the conservative strategy group (p = NS), with mortality of 11.5%
and 11.0% (p = NS), respectively. In this cohort, the mortality was 1.3%
in the 2nd year and 1.7% in the 3rd year from study entry. CONCLUSIONS.
TIMI II invasive and conservative strategies resulted in similar
favorable outcomes after 2 and 3 years. Mortality and reinfarction rates
in the two strategies were comparable. Deaths were infrequent in the 2nd
and 3rd years from study entry.
trial of delayed elective intervention v conservative treatment after
thrombolysis with anistreplase in acute myocardial infarction. SWIFT
(Should We Intervene Following Thrombolysis?) Trial Study Group.
OBJECTIVE--To see whether
early elective angiography with a view to coronary angioplasty or bypass
grafting of a stenosed infarct related vessel would improve outcome in
acute myocardial infarction treated by thrombolysis with anistreplase.
DESIGN--Randomised study of two treatment strategies with analysis of
results over 12 months. SETTING--21 district hospitals and regional
cardiac centres in Britain and Ireland. SUBJECTS--800 of 993 patients
presenting with clinical and electrocardiographic features of acute
myocardial infarction up to three hours after the onset of major
symptoms. TREATMENT STRATEGIES--Intravenous anistreplase 30 units
followed by a standard regimen of heparin, warfarin, and timolol and (in
patients so randomised) early angiography plus appropriate intervention.
MAIN OUTCOME MEASURE--Death or reinfarction within 12 months.
RESULTS--397 patients were randomised to receive early angiography plus
appropriate intervention (coronary angioplasty in 169 cases, coronary
grafting in 59) and 403 patients to receive conservative care (of these,
12 had angioplasty and seven bypass grafting during the initial
admission). By 12 months mortality (5.8% (23 patients) in the
intervention group v 5.0% (20) in the conservative care group; p = 0.6)
and rates of reinfarction (15.1% (60 patients) v 12.9% (52); p = 0.4)
were similar in the two groups. No significant differences in rates of
angina or rest pain were found at 12 months. Left ventricular ejection
fraction at three and 12 months was the same in both groups. Median
hospital stay was longer in the intervention group (11 days v 10 days; p
less than 0.0001). CONCLUSION--For most patients given thrombolytic
treatment for acute myocardial infarction a strategy of angiography and
intervention is appropriate only when required for clinical indications.
Variation across the United States in the Management of Acute Myocardial
England Journal of Medicine -- August 31, 1995 -- Volume 333, Number 9
Louise Pilote, Robert M.
Califf, Shelly Sapp, Dave P. Miller, Daniel B. Mark, W. Douglas Weaver,
Joel M. Gore, Paul W. Armstrong, E. Magnus Ohman, Eric J. Topol, for the
Differences in the management of acute myocardial infarction have been
reported among countries, but few studies have investigated this issue
in regions of the United States. METHODS: We compared the management of
acute myocardial infarction among census regions across the United
States, using data from the first Global Utilization of Streptokinase
and Tissue Plasminogen Activator for Occluded Coronary Arteries trial
(GUSTO-1) comprising 21,772 patients, and from the American Hospital
Association. RESULTS: We found substantial regional variation in the
management of acute myocardial infarction in the United States.
Beta-blockers (prescribed for a range of 55 to 81 percent of patients in
the various regions), nitrates (prescribed for 61 to 77 percent), and
angiotensin-converting-enzyme inhibitors (prescribed for 18 to 23
percent) were used most often in New England, whereas calcium-channel
blockers (31 to 42 percent) and lidocaine (14 to 43 percent) were used
least often there. Similarly, the proportion of patients undergoing
various cardiac procedures differed among regions (range for
angiography, 52 to 81 percent of patients; angioplasty, 22 to 35
percent; and coronary-artery bypass surgery, 9 to 17 percent) and was
lowest in New England. The regional use of cardiac procedures was
closely related to their availability, except in New England. After the
analysis was adjusted for clinical and hospital variables, patients in
New England were found to be less likely to undergo angiography than
patients in the other regions (odds ratio, 0.37; 95 percent confidence
interval, 0.32 to 0.42). There was no apparent relation between the use
of cardiac procedures and rates of recurrent infarction or death at 30
days or 1 year. CONCLUSIONS: There is substantial regional variation in
the use of cardiac medications and procedures to manage acute myocardial
infarction in the United States. The use and availability of cardiac
procedures are closely related. The management of acute myocardial
infarction in New England is atypical in that the relatively limited
availability of cardiac procedures does not account for their relatively
low use in that region.
the utilization of coronary angiography for elderly patients with an
acute myocardial infarction. An analysis using hierarchical logistic
Med Care (United States),
Jun 1995, 33(6) p625-42
AUTHOR(S): Gatsonis CA;
Epstein AM; Newhouse JP; Normand SL; McNeil BJ
ABSTRACT: This article
reports a study of variations in the utilization of angiography for
Medicare recipients who had an acute myocardial infarction. The study
cohort consisted of 1987 Medicare beneficiaries who had a recent acute
myocardial infarction. Variations were examined from three perspectives:
patient characteristics, regional practice patterns, and on-site
availability of the procedure. Factors associated with variation within
and among states were incorporated into the analysis using hierarchical
logistic regression models. The probability of angiography during the
first 90 days after an acute myocardial infarction was estimated as a
function of patient age, gender, race, and comorbidity for patients in
51 states (including the District of Columbia). Interstate differences
were examined in relation to geographic region and on-site availability
of angiography. Observed rates of angiography ranged between 13.8% and
38.3% (median, 24.7%). Variation was nearly threefold based on estimated
state probabilities of angiography for a patient with characteristics
set at the national average. Observed and estimated rates were lower in
northeastern states than in other parts of the United States. States
with more extensive onsite availability of angiography tended to have
higher angiography rates after adjusting for patient characteristics and
geographic region. Adjusted angiography rates were on average higher for
younger patients, males, and nonblacks. There was substantial interstate
variation in race differences, with states in the Southeast generally
having the largest differences. The adjusted black-to-nonblack odds
ratio ranged from a low of 0.41 to a high of 0.94. Interstate variation
in age and gender differences was moderate. The work reported in this
article illustrates the potential of hierarchical regression modeling as
a framework for the analysis of variations and some methodologic issues
connected with its implementation. Our results show that large
variations in the utilization of procedures can exist, despite uniform
insurance coverage and a relatively homogeneous patient cohort.
Aggressive use of angiography was highly variable across states as was
the degree of access to the procedure for blacks and nonblacks. The
state rate of on-site availability of angiography facilities was an
important predictor of utilization. Increased on-site availability of
angiography, however, was not associated with a reduction of differences
in access to the procedure.
in patient management and outcomes for acute myocardial infarction in
the United States and other countries. Results from the GUSTO trial.
Global Utilization of Streptokinase and Tissue Plasminogen Activator for
Occluded Coronary Arteries.
Werf F, Topol EJ, Lee KL, Woodlief LH, Granger CB, Armstrong PW, Barbash
GI, Hampton JR, Guerci A, Simes RJ, et al
of Cardiology, University Hospital Gasthuisberg, Leuven, Belgium.
differences in outcomes and patient management between patients in the
United States and outside the United States undergoing thrombolysis for
acute myocardial infarction. DESIGN, SETTING, AND PATIENTS--Patients in
the United States (n = 23,105) and 14 other countries (n = 17,916) were
randomized to receive streptokinase plus either subcutaneous or
intravenous (IV) heparin, accelerated recombinant tissue-type
plasminogen activator (rt-PA) plus IV heparin, or combined streptokinase
and rt-PA plus IV heparin. OUTCOME MEASURES--Differences in 30-day
mortality and patient management were compared among treatments and
between US and non-US patients. Treatment-by-country interactions were
assessed by logistic regression analyses. Expected mortality of US and
non-US patients was estimated using a predictive model and was compared
with observed mortality. RESULTS--Mortality reduction with accelerated
rt-PA vs streptokinase was greater in the United States (1.2% absolute
decrease vs 0.7% elsewhere), but the test for treatment-by-country
interaction against streptokinase was not significant (P = .30).
Benefits of accelerated rt-PA over combination therapy were observed in
the United States, but not in other countries (P = .02). Despite
differences in base-line characteristics and patient management, 30-day
mortality was not significantly different: 6.8% in the United States vs
7.2% elsewhere (P = .09). After adjustment for baseline differences,
observed vs predicted outcomes were slightly better in the United States
(6.8% vs 7.0%) than elsewhere (7.2% vs 7.0%), indicating that enrollment
in the United States was a marginally significant predictor of better
survival (P = .047). CONCLUSIONS--No significant evidence for a
differentially greater benefit of accelerated rt-PA over streptokinase
was found in US vs non-US patients. However, increased procedure and
treatment use in the United States was associated with only a small
decrease in short-term mortality. Long-term follow-up is required to
clarify the relationship between survival and the more intensive US
Thrombolysis or Primary Angioplasty Be the Treatment of Choice for Acute
England Journal of Medicine -- October 24, 1996 -- Volume 335, Number 17
community-based study reported in this issue of the Journal, Every et
al. compared the benefits of thrombolytic therapy with those of primary
coronary angioplasty for acute myocardial infarction. Although earlier
trials had suggested that primary angioplasty may be superior, Every et
al. found the two approaches essentially equivalent. How should
physicians choose between them?
We solicited two opposing
opinions, along with rebuttals, which we present in the first of a new
series of occasional pieces called "Clinical Debate." Lange
and Hillis argue that thrombolytic therapy should be the initial
therapy, whereas Grines favors coronary angioplasty. Is there a single,
right answer? Readers will have to judge for themselves.