The unstable angina national cooperative study was comprised of a high ... From the Texas Heart Institute, St. Luke's Episcopal Hospital and Clayton Foundation.
Commentary
CORONARY ARTERY BYPASS-ARE MULTICENTER COOPERATIVE RANDOM STUDIES MISLEADING? ROBERT J. HALL, M.D., EFRAIN GARCLA, M.D., VIRENDRA S. MATHUR, M.D., and CARLOS M. DE CASTRO, JR., M.D. Two multicenter cooperative random studies of angina pectoris, one on unstable angina' and a more recent study on stable angina,2 have reported no difference between the effects of medical and surgical therapy on long-term survival. Both reports, as well as an editorial by E. Braunwald,3 suggest the long-term survival of medically managed patients, 90% at two years for patients with unstable angina and 87% at three years for patients with stable angina (an average annual attrition of 5% and 4.33%, respectively), may be better than previously reported. Both cooperative studies, however, have certain features that raise concern regarding the validity of their conclusions. Both reports involved multiple institutions, eight in the unstable angina study and 13 in the stable angina study. The average number of patients randomized each year, according to medical and surgical therapy by each participating hospital, was relatively small: only 121 and 152 patients, respectively. Both studies excluded left main coronary artery disease and both excluded patients who had had a myocardial infarction within three4 to six months6 prior to randomization. Luminal diameter narrowing of 50% was the angiographic criterion in the stable angina study and 70%b in the unstable angina study. The unstable angina national cooperative study was comprised of a high percentage (65%o) of patients with single and double vessel disease ;4 and those excluded from randomization because of patient or physician preference have not been further characterized.5 Patients excluded from the Veterans Administration Cooperative Study2 have been accounted for in a previous report.6 Of patients eligible for randomization, slightly over one-quarter were "rejected"; of these, 8% by death, 38% "unwilling to enter study" and 48% for "other" but unspecified reasons. During the five years of the Veterans Administration Cooperative Study6 (only the last three of which make up the preliminary report of survival2), 80 patients (1.4% of the number screened or 7.9% of the number randomized) died from the time of initial screening but before randomization. The favorable long-term survival statistics in both of these studies, after randomization to medical therapy, probably resulted from excluding patients with more serious disease. Braunwald3 noted that the incidences of multi-vessel disease were high among those randomized in the Veterans Administration study. Yet, there is considerable variability of myocardial jeopardy between 50% and near total luminal diameter narrowing.
From the Texas Heart Institute, St. Luke's Episcopal Hospital and Clayton Foundation for Research Laboratory, Houston, Texas. Address for reprints: Robert J. Hall, M.D., Medical Director, Texas Heart Institute, P. 0. Box 20269, Houston, Texas 77025. 12
Cardiovascular Diseases, Bulletin of the Texas Heart Institute, Vol. 5, Number 1
Although each multicenter group excluded left main coronary disease, surgical mortality in both randomized studies was high. After excluding higher risk patients, those with left main coronary disease, unstable angina, those of the female sex, and including 44%o who were under 50 years, the Veterans Administration Cooperative group interpreted a 30-day operative mortality of 5.6% as representative of the period.2 In a consecu-tive series of 846 personally-observed patients7 who underwent coronary bypass surgery from late 1969 to June 1976, there was a 3.0% (2.6% in males) 30-day mortality. During the years 1972-1974, the years of the random studies, the overall 30-day mortality was 3.4% and in males was 3.0%o. In this total series, 66% of the patients were 50 years or older. Based upon 75%o or greater luminal diameter narrowing, triple vessel disease was present in 49%, double in 38%o and left main coronary disease in 8%. Eighty-two percent had angina, functional class III or IV (NYHA); 70% had prior myocardial infarction by ECG criteria; 17% had unstable angina (early mortality of 3.5%^ ); and 48%o had reduced ejection fractions. Fifty-three percent received three or more bypasses (2.53 per patient compared to 1.9 per patient in the Veterans Administration Cooperative study group). The five-year actuarial survival for these patients is 88.2%o (an average annual attrition, including surgery, of 2.36% per year). Although comparison of these survival data with older "noncurrent" medical controls has been criticized,3 the data7 compare favorably with "current" medical survival curves,1 2 both reports of which are based upon patient populations that excluded the major high risk categories cited earlier (Figure 1). ANGINA-SURVIVAL CURVES COMPARISON RANDOM STABLL AND KANUUM UNbIAbLL SERIES vs TEXAS HEART INSTITUTE SURGICAL SERIES
In0 98* x
96|
'J
*-* StableAnginaNedicalP, ;VAH-4.33%/Year a-o Stable Angina,SurgicalFl ;VAH-4 0%/YeOrSl-3 YEARS Y-T Unstable Angina,Medical R, ;NHLI-4.55/Year 22 YEARS
V-V Unstable Angina,Surgical Ft ;NHLI-5.2%/Yei THI 846 Cases, Surgical F ;2.46%/YeOar -\x P, -5 YEARS - THI 143 Cases, Unstable
\-x
Angina,SurgcolYearJ
132.44% K
> 94cn
0
e 92
V~~~~~~~~~~~~~ 90
88
88
x
878%
\877% %87%
30d 1/2
2
3
4
5
YFARS
Fig. 1. Actuarial survival curves for the two reported randomized medical and surgical series are shown. The five-year actuarial survival curves of the total "personally observed" surgical bypass series and the subset of patients with unstable angina, surgically managed, are plotted for comparison. The latter surgical series demonstrate survival characteristics more favorable than "current" medical controls from the random studies.
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The issue of prolonging life following coronary bypass surgery is not yet closed. For the reasons we have described, the multicenter cooperative random studies tend to confuse rather than clarify the issues.
REFERENCES 1. National Cooperative Study Group of National Heart, Lung and Blood Institute: In Acute Unstable Angina: Medical Approach Better Than Previously Reported . Clinical Trends in Cardiology 6:1-3, 1977 2. Murphy ML, Hultgren HN, Detre K et al: Treatment of chronic stable angina: A preliminary report of survival data of the randomized Veterans Administration Cooperative Study. N Eng J Med 297:621-627, 1977 3. Braunwald E: Coronary-artery surgery at the crossroads. N Eng J Med 297:661-663, 1977 4. Russell RO, Moraski RE, Kouchoukos N et al: Unstable angina pectoris: National Cooperative Study Group to compare medical and surgical therapy. I. Report of protocol and patient population. Am J Cardiol 37:896-902, 1976 5. Scheidt SS: Unstable angina: Medical management of surgery? Editorial and comment. Cardiovascular Medicine 2:541-543, 1977 6. Detre K, Hultgren H, Takaro T: Veterans Administration Cooperative Study for coronary arterial occlusive disease. III. Methods and baseline characteristics, including experience with medical treatment. Am J Cardiol 40:212-225, 1977 7. Hall RJ, Garcia E, Mathur VS et al: Factors influencing early and late survival after aortocoronary artery bypass: A preliminary report. Cardiovasc Dis, Bull Texas Heart Inst 4:120-128, 1977
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