Outcomes in patients with acute non-Q-wave myocardial infarction randomly
assigned to an invasive as compared with a conservative management strategy
| Authors |
Boden W, O'Rourke R, Crawford M, Blaustein A, Deedwania
P, Zoble R, Wexler L et al, for the VANQUISH Trial investigators. |
| Source |
New England Journal of Medicine. 338:1785-92. June
18, 1998. |
| Institutions |
Multiple Veterans Affairs Medical Centers in the United
States. |
| Support |
VA Cooperative Studies Program and Hoechst Marion Roussel. |
Background
Patients with acute non-Q-wave myocardial infarctions are at a relatively
high risk for ischemic complications (re-infarction and angina) both early
and late post-infarct. These patients are often managed with early angiography,
particularly in the United States, despite a lack of clear evidence for
benefit with this approach. The VA Non-Q-Wave Infarct Strategies in Hospital
study (VANQWISH) was designed to investigate this issue. Patients post
NQMI were randomized to an invasive (early angiography) or a conservative
(angiography when clinically indicated) arm. Endpoints were early and late
re-infarction and mortality. |
Methods
Patients
Inclusion criteria: evolving acute myocardial infarction with
CPK-MB greater than 1.5 times normal.
Exclusion criteria: new abnormal Q-waves (or R-waves in V1-V2)
on serial EKG's (at least one taken 48 hours after admission); ischemia
at rest and severe heart failure despite medical therapy.
Intervention
Patients were randomized to an early invasive or early conservative
strategy and stratified according to age, prior MI, use of thrombolytics,
anterior MI location and ST-segment depression on entry EKG.
All patients received 325 mg enteric coated aspirin and long-acting
diltiazem (180 to 300 mg daily). Other therapy, including thrombolytic
therapy, was given as judged necessary.
Patients assigned to the early invasive group underwent angiography
soon after randomization; baloon angioplasty was recommended for single
vessel disease, bypass surgery for patients with multivessel disease, but
the decision was left to the local study investigators.
In the early conservative group, patients underwent radionuclide ventriculography
and thallium perfusion scanning (planar or SPECT, exercise or dipyridamole).
Coronary angiography (and revascularization, when deemed appropriate) was
performed if any of the following criteria were met:
-
recurrent angina with EKG changes
-
at least 2 mm ST segment depression on the pre-discharge exercise test
-
ischemia with increased lung uptake or ischemia in two or more vascular
territories on the stress thallium scan
Analysis
Patients were seen one month after discharge and at three month intervals
thereafter; trial enrollment began in 1993 and ended on December 31, 1995;
follow-up was until December 31, 1996.
The primary endpoint was death or nonfatal myocardial infarction; other
endpoints were overall mortality and complications from procedures.
|
Results
Patients
2738 patients with non-Q-wave infarctions were identified; 247 were
excluded because of early ischemic complications. The study population
consisted of 920 patients (34% of the 2738 patients with NQMI), 462 randomized
to the invasive strategy, 458 to the conservative strategy.
Baseline characteristics were well-matched between the groups and included
(average of the two groups when not specified):
-
Age 62 years; 97% male sex.
-
Smokers: 43%; hypertensive: 54%; hypercholesterolemic: 17%; IDDM: 26%;
prior MI: 43%.
-
Medications prior to the NQMI: nitrates: 31%; beta-blockers: 22%; calcium
antagonists: 36%; aspirin: 46%; lipid-lowering drugs: 13%.
-
MI location by ECG was inferior or posterior in approximately 40% of patients.
Primary end points
During an average 23 months of follow-up, a total of 152 events occurred
in the invasive group (80 deaths and 72 non-fatal infarctions), vs.
139 events in the conservative group (59 deaths and 80 infarctions), not
significantly different (p=0.35).
During the early post-MI period, however, patients in the conservative
strategy group fared significantly better, and this benefit diminished
gradually. At one year, there were 111 events in the invasive group vs.
85 in the conservative group (p=0.05) and 58 vs. 36 deaths (p=0.025).
Angiography, revascularization and mortality
|
Invasive group
(462 patients) |
Conservative group
(458 patients) |
| Total undergoing coronary angiography |
96% |
48% |
| Angiography before hospital discharge |
94% |
24% (approximately half for recurrent angina; half for abnormal stress
tests) |
| Double, triple or left main disease among patients who underwent
angiography |
74% |
80% |
| Revascularization performed |
44% of the group (approximately half underwent CABG) |
33% of the group (approx. 2/3 had CABG) |
| 30-day mortality among revascularized patients |
0/98 PTCA
11/95 CABG
0/11 PTCA + CABG
Total: 11/204 |
2/55 PTCA
3/87 CABG
1/10 PTCA + CABG
Total: 6/152 |
Among the 52% of patients in the conservative group who did not undergo
angiography, 1 year mortality was 6%.
Subgroup analyses
There was no evidence for an advantage of the invasive strategy in
any of the subgroups studied: by MI location, use of thrombolytics, prior
MI, ST-segment depression or age.
|
Author's discussion
The authors conclude that there is no benefit to early and systematic
angiography in patients with non-Q-wave myocardial infarction and, in fact,
there was evidence of detriment with this approach during the first year
post-MI. Absence of automatic, early angiography does not mean blindly
applying medical therapy, however, since angiography was performed when
indicated (in half of all patients, ultimately). Thus, this was not
a trial of medical versus interventional therapy post-non-Q-wave MI.
Limitations of the trial include the fact that it studied almost exclusively
men and was conducted before coronary stenting and glycoprotein receptor
antagonists were widely available.
|
Editorial
In an accompanying editorial, Lange and Hillis note that the results of
this trial are in accord with the results of studies looking at the role
of early angiography in other acute coronary syndromes (unstable angina
and post-thrombolytic therapy). None of these studies found a significant
advantage to early, systematic intervention. Despite these results,
an aggressive approach with early angiography is often taken, particularly
in the United States. Some of the reasons for this are discussed in the
editorial.
|
|
Reader Comments
Date: Thu, 30 Jul 1998
From: Sandra & Colin Rose <colros@odyssee.net>
Exactly the same comments could be made for patients
with chronic angina. The RITA-2 study showed almost identical results to
VANQWISH study but in patients with stable angina. It's about time
a moratorium were declared on all elective angioplasties in patients with
either chronic symptoms or post MI until it can be determined by controlled
studies in a few centers exactly which patients benefit from this procedure.
We are wasting a lot of resources and doing a lot of harm in a futile effort
to deal with the small proportion of the total atheroscerotic burden which
appears on angiograms.
Dr. Colin Rose
Montreal
I agree that the exact benefit of angioplasty
has not yet been adequately determined and that this procedure is over-utilized,
particularly in the US. VANQWISH was not designed to look at this issue
directly, however, but rather at the utility of performing angiography
(and then revascularization) routinely post NQWMI or only when indicated
by evidence of ischemia. -- mj
Date: Fri, 14 Aug 1998
From: <SBerger475@aol.com>
I think most of us agree that the degree of ischemia post-MI (Q-wave
or non-Q wave) is very significant in our management, thus the issue scratched
at by VANQUISH is whether patients after non-Q wave MI who have no obvious
residual ischemia can be managed conservatively. It would seem this
answer is probably yes, though I agree the impact of stent therapy will
need to be taken into account. Even more importantly, however, is
the issue of "optimal" medical therapy, including the proper risk analysis
and treatment of LDL cholesterol, LVH, tobacco addiction, hypertriglyceridemia,
homocysteinemia, etc. Our understanding of the impact of these
risks is advancing as fast or faster than our coronary intervention
technologies and sadly our implementation of proven "medical therapy" is
no where near ideal!
From the corresponding author of this study, Dr. William Boden:
Date: Fri, 18 Sep 1998
From: "Boden, William E" <William.Boden@med.va.gov>
I agree with Mike Jacobson's response to Dr. Rose. VANQWISH was
not designed to compare myocardial revascularization to medical therapy,
but rather two strategies (angiography with revascularization, if feasible
or necessary versus. medical therapy, non-invasive testing and subsequent
angiography + revascularization if ischemia developed or was induced).
Thus, since we did not really adress this issue of revascularization per
se in a prospective, randomized fashion, I think it would be unfair to
call for a moratorium on interventional procedures.
But, VANQWISH shows that 52% of the conservative strategy patients did
not require coronary angiography during a 44 month follow-up, and hence,
would be regarded as a relatively low-risk subset. This means that
one CAN risk stratify, and that we need to use non-invasive testing as
part of an ischemia-guided strategy for NQMI management.
Finally, I agree with Dr. Berger that medical therapy in VANQWISH, by
1998 standards, was not up to speed. But, since the trial began in
1993 before any of the major statin trials were published, and before GP
IIb/IIIa inhibitors were available, one can certainly make the point that
outcomes in the conservative arm might have been even better, had we aggressively
altered lipids or had access to other, newer agents. I don't know
what impact stents will have; bear in mind that, using only standard
balloon angioplasty, we had 0% 30-day mortality in the invasive group,
and only a 1.3% overall 30-day mortality among the 153 patients who underwent
PTCA. It might be hard to improve upon these numbers with stents...
--WEB
[Dr. Boden also pointed out an error I made in the summary -- I
listed the p-value for the event rates at one year
as 0.5 instead of 0.05; I have rectified this mistake -- mj].
November 19, 1998
Letters
to the editor (November 5, 1998 NEJM) concerning this study.
A number of important objections are raised, all of which are dealt
with by the authors of the study. These include the problems of suboptimal
therapy in both groups, low rates of intervention in the aggressive group,
high event rates in patients undergoing CABG and the question of myocardial
viability studies.
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