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. 


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.



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. 


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
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. 



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. 


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. 


This study of 920 predominantly male patients  with acute non-Q-wave myocardial infarction found no benefit to the routine, systematic performance of coronary angiography over an approach that performed angiography only when indicated by spontaneous or stress-test provoked ischemia. In fact, patients randomized to the aggressive therapy arm fared worse over the first year of follow-up (the difference was not statistically significant thereafter). 

Coronary stents were not in widespread use during most of the trial. The rapidly evolving nature of invasive cardiovascular therapy is an unavoidable problem with most studies like this, but medical therapy also improves over time, which should provide some balance. 
Although this study will probably not alter the behavior of the most "invasive" cardiologists, it will give much needed support to those who are more comfortable with the more conservative approach. 

July 30, 1998 


References related to this article from the NLM's PubMed database. 

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 

    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... 

[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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