Background. Thrombolysis has altered treatment of acute myocardial infarction (AMI). Therefore, reevaluation of predictors of outcome and treatment strategies is appropriate. Methods and Results. Clinical variables collected prospectively for the 3,339 patients of the Thrombolysis in Myocardial Infarction II study were analyzed retrospectively to identify predictors of clinical events at 42 days and earlier and to identify subgroups in which an invasive or conservative strategy might be superior. Pulmonary edema/cardiogenic shock presented as the strongest independent correlate with death (relative risk, 6.0). In two subgroups, mortality differed between the invasive and conservative strategies: 1) Patients with versus without prior AMI had a higher mortality in the conservative strategy (11.5% versus 3.5%, p<0.001); in the invasive strategy, the mortality rates were similar (6.0%o and 5.1%). 2) Patients with diabetes mellitus and no prior AMI had a higher mortality in the invasive than in the conservative strategy (14.8% versus 4.2%, p<0.001). Reinfarction was not independently correlated with baseline characteristics except with history of angina (relative risk, 1.9). Mortality was lower in current smokers and ex-smokers versus never-smokers (3.6% and 4.8% versus 8.0%, p<0.001). Current smokers had a lower risk profile (p<0.001), including age, pulmonary edema/cardiogenic shock, history of hypertension, and diabetes. The rate of reinfarction was lower in current smokers versus ex-smokers and never-smokers (4.6% versus 8.3% and 8.8%, p<0.001). "Not current smoker" was an independent correlate with reinfarction (relative risk, 1.9). The coronary anatomy did not differ among the current smokers, ex-smokers, and never-smokers. Conclusions. The strong independent correlation of pulmonary edema/cardiogenic shock with death suggests that thrombolysis is not sufficient to improve survival in these patients. The higher mortality in patients with versus without priorAMI in the conservative strategy suggests that early catheterization and revascularization of these patients might be beneficial. Conversely, the higher mortality in diabetics without prior AMI in the invasive than in the conservative strategy suggests that early aggressive management might not be suitable in this subgroup except for clinical indications. Reinfarction was not predictable by clinical variables except by history of angina. The finding that "not current smoker" was

The Coronary Artery Surgery Study (CASS) randomized 780 patients to an initial strategy of coronary surgery or medical therapy. Of medically randomized patients, 6% had surgery within 6 months and a total of 40%o had surgery by 10 years. At 10 years, there was no difference in cumulative survival (medical, 79%, vs. surgical, 82%; NS) and no difference in percentage free of death and nonfatal myocardial infarction (medical, 69%o vs. surgical, 66%; NS). Patients with

To examine whether digitalis use is associated with an increased mortality in certain highrisk subsets of patients with coronary artery disease, we analyzed the data of 14,547 patients in the Coronary Artery Surgery Study (CASS) registry who had significant coronary artery stenosis (¢ 70% narrowing) and received medical treatment for their disease. At the time of entry, 2600 patients (18%) Were taking a digitalis preparation. At a mean follow-up of 41/2 years, the cumulative mortality rate for these patients was 18%, compared with 5% for the 11,947 patients not taking digitalis (p < 0.001). Univariate analysis showed significant differences between the two groups in the following baseline variables: prior infarction, multiple infarction, age, degree of congestive heart failure (CHF), extent of disease, cardiomegaly and wall motion abnormalities. Cox regression analysis of the entire population failed to show digitalis to be one of the 13 variables independently predictive of survival. High-risk subsets of patients with CHF, myocardial infarction within 2 months preceding entry and patients with prior cardiac arrest or arrhythmia were analyzed separately by Cox analysis. The number of vessels diseased and left ventricular wall motion were the two most important variables predictive of survival in each group. Digitalis therapy failed to enter the final model in any subset of patients studied. The expected mortality of our study population classified according to the degree of CHF was similar to the observed mortality whether the patients were on or off digitalis. This study fails to confirm the findings of earlier reports showing a substantial mortality associated with digitalis use in certain high-risk subsets of patients with coronary artery disease. Although we could demonstrate no benefit in terms of survival for patients receiving digitalis in this population study, we conclude that digitalis therapy is not likely to be an independent risk factor contributing significantly to mortality in patients with coronary artery disease.

The prevalence of coronary artery stenoses 2 70% or left main stenosis > 50% was evaluated in 20,391 patients who underwent angiography in the Coronary Artery Surgery Study from 1975-1979. After the patients with unstable angina or myocardial infarction were excluded, the disease prevalence in the 8157 patients with definite angina, probable angina, and nonspecific chest pain was 93%, 66% and 14% in men and 72%, 36% and 6% in women (p < 0.001). The age and sex of the patients and character of chest pain were important determinants of disease prevalence and severity. Left main or three-vessel coronary disease occurred in more than 50% of middle-aged

In 380 patients, coronary calcifications were quantified by electron beam tomography and compared with the predicted 10-year cardiovascular event risk determined by the Framingham equation, Adult Treatment Panel III tables, and the PROCAM algorithm. The correlation between the amount of calcium and the predicted cardiac event risk was low (correlation coefficient range 0.19 to 0.28). The assessment of coronary calcium may thus potentially yield information that is additive to the analysis of traditional risk factors.

Objectives. The Coronary Artery Surgery Study (CASS) required participants to undergo follow-up angiography at 5 years to identify clinical and angiographic features associated with progression of coronary artery disease.Background. The CASS randomized 780 patients at 11 participating clinical centers between an initial strategy of medical therapy versus bypass surgery. Five clinical sites accomplished follow-up angiography in >50% of their randomized subjects within a 42- to 66-month period after the entry arteriogram (n 314).Methods. Qualified clinical site angiographers, using side by side film review, evaluated an average of 13 segments/patient on both arteriograms for initial stenosis severity, morphologic features, lesion location and occurrence of disease progression or occlusion. Progression was defined as further definite narrowing by greater-than-or-equal-to 15% and occlusion as lesion progression to greater-than-or-equal-to 98%. Lesions were subcategorized as to whether they were univariate and had or had not been treated with bypass surgery. Multivariate logistic regression analyses were performed.Results. For nonbypassed segments, right coronary artery and left anterior descending artery proximal and midlocations were associated with disease progression. For stenosis-containing segments, the initial severity, a non-left anterior descending artery location and increased treadmill duration predicted progression. Segment occlusion was associated with initial lesion severity, right coronary artery location and subsequent interval myocardial infarction. There were few predictors of progression or occlusion in bypassed arteries, other than initial lesion severity.Conclusions. Univariate and multivariate associations with lesion progression and occlusion included diabetes, lesion location, elevated cholesterol level, interval infarction and lesion morphology. These angiographic results, collected in a prospective trial, are consistent with known risk factors.

The Coronary Artery Surgery Study (CASS) includes 780 patients with mild or moderate stable angina pectoris or asymptomatic survivors of a myocardial infarction who were randomized to either medical or surgical therapy and 1,319 patients who were eligible for randomization but were not randomized (randomizable patients). There were no substantial aggregate differences observed in any of the survival comparisons after 10 years of follow-up study between the randomized and randomizable patients assigned to the medical (79% versus 80%) or surgical (82% versus 81%) groups or in patient subgroups stratified according to coronary artery disease extent and left ventricular ejection fraction. Cox regression analyses were done with independent variables known to be predictors of survival, including surgical versus medical therapy and randomized versus randomizable group, to test the null hypothesis of a mortality difference between medical versus surgical assignment according to group assignment (randomized versus randomizable). In no case did the initial group category enter as a significant predictor of survival. The results in the randomizable group reinforce those in the randomized group with respect to the medical versus surgical comparison. Two subgroups are identified with a significant surgical advantage: 1) patients with proximal left anterior descending coronary artery stenosis greater than or equal to 70% and an ejection fraction less than 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction less than 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p less than 0.05). After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial.

This nonrandomized study compared the results of early coronary artery bypass grafting to those of initial medical therapy in a group of 2,023 patients with severe angina pectoris and 2 major epicardial coronary arteries having greater than or equal to 70% diameter luminal narrowing. Medical therapy was selected for 706 patients, and 1,317 patients were treated by coronary artery bypass grafting. The 6-year survival rate was 76% for patients treated medically and 89% for patients treated surgically (p less than 0.0001). Cox multivariate analysis showed that surgical treatment was a beneficial independent predictor of survival (p less than 0.001). For patients with 2-vessel coronary artery disease who had Canadian Heart Association class III and IV angina at presentation, surgical therapy provided a survival advantage for patients with impaired left ventricular function and proximal narrowing of 1 or more coronary arteries.

The relation between vasectomy and renal disease was examined in the data collection phase of a study of vasectomy and coronary artery disease. The date of onset and type of urological disease was obtained for 11,205 men enrolled in the US Coronary Artery Surgery Study. Urolithiasis was the most common reported urological disease. The relative risk for calculi in men who had had a vasectomy ranged from 2.6 for patients 30-35 years old to 1.3 for those aged 55-65. The age-adjusted relative risk was 1.67 (p less than 0.001).

Angiographic evidence of coronary artery disease was present in 16,002 patients in the Coronary Artery Surgery Study (CASS) registry. Of these patients, 551 had a history of cardiac arrest before enrollment angiography. Cardiac arrest was a complication of acute myocardial infarction (AMI) in 372 patients (68%). Electrocardiographic documentation of the responsible rhythm was available in 283 patients. Ventricular fibrillation (VF) was present in 112 (60%), ventricular tachycardia (VT) in 41 (22%) and both VT and VF in 26 (14%) patients. Stepwise linear discriminant analysis comparing the 551 cardiac arrest patients with the other 15,451 patients selected left ventricular wall motion score (F = 265), use of digitalis (F = 71), impaired blood supply to any segment (F = 16) and particularly to the anterior wall (F = 11) as discriminating variables associated with cardiac arrest. Patients with cardiac arrest occurring as a complication of AMI were younger (F = 12), had greater impairment of coronary blood supply (F = 7) and were more likely to be on a cholesterol-lowering diet (F = 16) than were patients with arrest remote from infarction. Comparison of patients with VT versus those with VF showed a positive association of VT with age (F = 8), a trend toward worse left ventricular function and presence of a left ventricular aneurysm, but no difference in severity and collateralization of coronary artery disease. It is concluded that cardiac arrest is related to the extent of myocardial damage. Cardiac arrest in the context of AMI is associated with somewhat more extensive distal coronary disease than cardiac arrest remote from AMI, which is more highly correlated with prior infarction and more clinically manifest heart failure. VF was less frequently associated with chronic myocardial scar and VT, raising the possibility that other factors such as ischemia could be contributory.

The effect of medical and surgical treatment on subsequent sudden cardiac death was assessed in 13,476 patients in the Coronary Artery Surgery Study registry who had significant coronary artery disease, operable vessels, and no significant valvular disease. (Patients were assigned to medical or surgical therapy on the basis of clinical judgment and not according to a randomization scheme; therefore, biases associated with unknown variables could not be evaluated.) Sudden cardiac death occurred in 452 patients (3.4%) during a mean follow-up of 4.6 years. Five year survival free of sudden death for medically treated patients was 94 +/- 0.3%, and that for surgically treated patients was 98 +/- 0.2% (p less than .0001). Twelve baseline clinical, electrocardiographic, and angiographic variables were significantly different between patients alive at the last follow-up and those suffering sudden death. Data on these variables were available for 11,508 patients. Sudden death occurred in 257 (4.9%) of 5258 medically treated and 101 (1.6%) of 6250 surgically treated patients. In a high-risk patient subset with three-vessel disease and history of congestive heart failure, 91% of surgically treated patients had not suffered sudden death compared with 69% of medically treated patients. After Cox survival analysis was used to correct for baseline variables, surgical treatment had an independent effect on sudden death (p less than .0001). This reduction was most pronounced in high-risk patients.

We compared the results of coronary artery bypass surgery with those of medical therapy alone in 1491 nonrandomized patients 65 years of age or older. Cumulative survival at six years (adjusted for major differences in important base-line characteristics) was 79 per cent in the surgical group and 64 per cent in the medical group (P less than 0.0001). At five years, chest pain was absent in 62 per cent of the surgical group and 29 per cent of the medical group (P less than 0.0001). Analysis by the Cox proportional-hazards model suggested an independent beneficial effect of surgery on survival (P less than 0.0001). Patients were divided into risk quartiles on the basis of preoperative predictors of survival identified by the Cox model. Surgical benefit was greatest in "high-risk" patients (those in the two quartiles containing patients with the poorest prognosis). Among 234 "low-risk" patients with mild angina, relatively good ventricular function, and no left main coronary artery disease, there was no survival difference between those treated medically and those treated surgically. We conclude that in specific higher-risk subsets of non-randomized patients 65 years of age or older, coronary bypass surgery appeared to improve survival and symptoms in comparison with medical therapy alone. These conclusions must be tempered by consideration of the limitations of nonrandomized studies, particularly since patients in the two treatment groups differed substantially with regard to important base-line characteristics.

A preliminary report is presented of a prospective randomized trial conducted by eight cooperative institutions under the auspices of the National Heart and Lung Institute to compare the effectiveness of medical and surgical therapy in the management of the acute stages of unstable angina pectoris. To date 150 patients have been included in the randomized trial, 80 assigned to medical and 70 to surgical therapy; the clinical presentation, coronary arterial anatomy and left ventricular function in the two groups are similar. Some physicians have been reluctant to prescribe medical or surgical therapy by a random process, and the ethical basis of the trial has been questioned. Since there are no hard data regarding the natural history and outcome of therapy for unstable angina pectoris, randomization appears to provide a rational way of selecting therapy. Furthermore, subsets of patients at high risk may emerge during the process of randomization. The design of this randomized trial is compared with that of another reported trial. Thus far, the study has shown that it is possible to conduct a randomized trial in patients with unstable angina pectoris, and that the medical and surgical groups have been similar in relation to the variables examined. The group as a whole presented with severe angina pectoris, either as a crescendo pattern or as new onset of angina at rest, and 84 percent had recurrence of pain while in the coronary care unit and receiving vigorous medical therapy. It is anticipated that sufficient patients will have been entered into the trial within the next 12 months to determine whether medical or surgical therapy is superior in the acute stages of unstable angina pectoris.

The 3 year cumulative survival rate of 1,492 patients with left main coronary artery disease (50 percent or greater stenosis of luminal diameter) enrolled in the Collaborative Study in Coronary Artery Surgery (CASS) was 91 percent for the surgical group and 69 percent for patients treated medically (p less than 0.0001). Mortality was significantly greater in patients with impaired left ventricular function. The difference between medical and surgical therapy was significant for patients who had normal, moderately abnormal and severely impaired left ventricular function and for patients with stenosis of the left main coronary artery of 50 to 59, 60 to 69, 70 to 79 and 80 percent or greater. Aortocoronary bypass surgery did not significantly improve survival in patient subgroups who had (1) a nonstenotic dominant right or balanced coronary circulation, (2) a stenotic dominant right coronary artery and normal left ventricular function, and (3) left main coronary stenosis of 50 to 59 percent and normal or mildly abnormal left ventricular function. The Cox proportional hazards model was used to select baseline variables that were independent predictors of long-time mortality. The model selected left ventricular score, age, congestive heart failure score, hypertension, percent left main coronary arterial stenosis and coronary arterial dominance as the baseline variables most predictive of long-term survival. A clinical and angiographic prognostic risk index developed from these six baseline variables showed significantly improved survival for the surgical cohort in each of four risk categories. In the best and worst risk category, the 3 year survival rate was 97 and 82 percent, respectively, for the surgical group and 85 and 34 percent, respectively, for the medical group (p less than or equal to 0.0002). The data from this observational study show that coronary bypass surgery prolongs life in most patients with left main coronary artery disease, particularly those who have severe narrowing of the left main coronary artery or impaired left ventricular function. The results permit a better understanding of the natural history of left main coronary artery disease and permit a more accurate estimate of long-term survival for individual patients through the use of a clinical-angiographic risk index.