Long-term survival of medically treated patients in the Coronary Artery Surgery Study (CASS) Registry.

BACKGROUND: This study describes the impact of clinical, angiographic, and demographic characteristics on the long-term survival of Coronary Artery Surgery Study (CASS) patients while they were under medical treatment. Revascularization rates for the population are also provided. METHODS AND RESULTS: All CASS patients who had not received heart surgery before enrollment (23,467 patients) were included in this survival analysis while they were under medical treatment or surveillance. Follow-up time ranged from 0 to 17 years (median, 12 years). Long-term vital status is known for 95.8% of these patients. Log-rank tests, Kaplan-Meier survival curves, and Cox proportional-hazards regression are used to describe and assess the impact of patient characteristics on survival. Characteristics that had a significant impact on survival, in order of observed explanatory power, are age, number of diseased vessels, congestive heart failure score, smoking history, ejection fraction, sex, presence of left main coronary artery disease, presence of diabetes, left ventricular wall motion score, presence of other illnesses, history of myocardial infarction, and presence of left main equivalent disease. Overall, 12-year survival for patients with zero-, one-, two- and three-vessel disease is 88%, 74%, 59%, and 40%, respectively. Twelve-year survival for patients with at least one diseased vessel and ejection fractions in the ranges of 50% to 100%, 35% to 49%, and 0% to 34% is 73%, 54%, and 21%, respectively. High myocardial jeopardy, high anginal class, and two or three proximal diseased vessels characterize the profile of patients most likely to have received surgical treatment during follow-up. CONCLUSIONS: These results contribute to the understanding of the natural history of coronary artery disease and are also of historical interest. The poor survival of patients with three-vessel disease and low ejection fractions continues to emphasize the importance of considering revascularization for these patients.

Effect of coronary artery bypass graft surgery on survival: overview of 10-year results from randomised trials by the Coronary Artery Bypass Graft Surgery Trialists Collaboration.

We carried out a systematic overview using individual patient data from the seven randomised trials that have compared a strategy of initial coronary artery bypass graft (CABG) surgery with one of initial medical therapy to assess the effects on mortality in patients with stable coronary heart disease (stable angina not severe enough to necessitate surgery on grounds of symptoms alone, or myocardial infarction). 1324 patients were assigned CABG surgery and 1325 medical management between 1972 and 1984. The proportion of patients in the medical treatment group who had undergone CABG surgery was 25% at 5 years, 33% at 7 years, and 41% at 10 years: 93.7% of patients assigned to the surgery group underwent CABG surgery. The CABG group had significantly lower mortality than the medical treatment group at 5 years (10.2 vs 15.8%; odds ratio 0.61 [95% CI 0.48-0.77], p = 0.0001), 7 years (15.8 vs 21.7%; 0.68 [0.56-0.83], p < 0.001), and 10 years (26.4 vs 30.5%; 0.83 [0.70-0.98]; p = 0.03). The risk reduction was greater in patients with left main artery disease than in those with disease in three vessels or one or two vessels (odds ratios at 5 years 0.32, 0.58, and 0.77, respectively). Although relative risk reductions in subgroups defined by other baseline characteristics were similar, the absolute benefits of CABG surgery were most pronounced in patients in the highest risk categories. This effect was most evident when several prognostically important clinical and angiographic risk factors were integrated to stratify patients by risk levels and the extension of survival at 10 years was examined (change in survival -1.1 [SE 3.1] months in low-risk group, 5.0 [4.2] months in moderate-risk group, and 8.8 [5.4] months in high-risk group; p for trend < 0.003). A strategy of initial CABG surgery is associated with lower mortality than one of medical management with delayed surgery if necessary, especially in high-risk and medium-risk patients with stable coronary heart disease. In low-risk patients, the limited data show a non-significant trend towards greater mortality with CABG.

Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Participating Investigators and Staff.

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 > or = 15% and occlusion as lesion progression to > or = 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.

Ten-year follow-up of survival and myocardial infarction in the randomized Coronary Artery Surgery Study.

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% 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% vs. surgical, 66%; NS). Patients with an ejection fraction of less than 0.50 exhibited a better survival with initial surgery treatment (medical, 61% vs. surgical, 79%; p = 0.01). Conversely, patients with an ejection fraction greater than or equal to 0.50 exhibited a higher proportion free of death and myocardial infarction with initial medical therapy (medical, 75% vs. surgical, 68%; p = 0.04) although long-term survival remained unaffected (medical, 84% vs. surgical, 83%; p = 0.75). There were no significant differences either in survival and freedom from nonfatal myocardial infarction, whether stratified on presence of heart failure, age, hypertension, or number of vessels diseased. Thus, 10-year follow-up results confirm earlier reports from CASS that patients with left ventricular dysfunction exhibit long-term benefit from an initial strategy of surgical treatment. Patients with mild stable angina and normal left ventricular function randomized to initial medical treatment (with an option for later surgery if symptoms progress) have survival equivalent to those patients randomized to initial surgery.

Coronary Artery Surgery Study (CASS): comparability of 10 year survival in randomized and randomizable patients.

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.

Myocardial revascularization for unstable angina pectoris.

We reviewed 14 reports from 1978 to 1988 of 6,136 patients with unstable angina pectoris treated by coronary artery bypass grafting (CABG). The mean age was 56.8 years, and 23% were female. Mean operative mortality in the 14 reports was 3.7% (1.2-8.5%). The mean incidence of perioperative myocardial infarction was 9.9% (3.8-17%). The mean incidence of postoperative low cardiac output was 16% (8-35%). No risk factors for morbidity or mortality different from those observed in patients with chronic stable angina were identified. Clinical subgroups of the heterogeneous group of patients with unstable angina pectoris are associated with different prognoses and treatment results. Variable pathological changes are associated with these subgroups. Reductions in morbidity and mortality of those patients undergoing CABG may require better preoperative management of the underlying pathological process and improved myocardial preservation at the time of CABG. Angina relief, improved survival, and reduction in late nonfatal myocardial infarction is similar to that observed in patients with chronic stable angina after CABG.

Asymptomatic left main coronary artery disease in the Coronary Artery Surgery Study (CASS) registry.

Left main coronary artery disease (i.e., greater than or equal to 50% stenosis) was found in 1,477 of 20,137 patients in the Coronary Artery Surgery Study (CAS) registry. Of these patients, 53 (3.6%) were asymptomatic. Asymptomatic and symptomatic patients were similar in regard to 1) severity of left main coronary artery stenosis (67% vs. 70%), 2) extent of proximal coronary artery disease (no differences in number of or severity of proximal stenoses), 3) left ventricular end-diastolic pressure (13 mm Hg vs. 14 mm Hg), 4) left ventricular wall motion score 9.1 vs. 8.7), and 5) number of coronary artery segments with greater than 70% stenosis (4.4 vs. 4.8). Among the asymptomatic patients, 47% received medical and 49% received surgical treatment. In the symptomatic group, 20% received medical and 78% received surgical therapy. The survival rate 5 years after surgery for treatment of left main coronary artery stenosis was 84% for the symptomatic patients and 88% for the asymptomatic patients (p = NS). Medical management of left main coronary artery disease produced a 5-year survival rate of 57% for asymptomatic patients and 58% for symptomatic patients. Within the asymptomatic subgroup, 88% of those surgically treated survived 5 years, whereas only 57% of those medically treated survived 5 years (p = 0.02). Thus, for CASS patients with left main coronary artery disease, the percentage of those that were asymptomatic is low (3.6%); asymptomatic and symptomatic patients with left main coronary artery disease had no significant difference in severity of left main coronary artery stenosis, extent of overall coronary artery disease, or left ventricular function.(ABSTRACT TRUNCATED AT 250 WORDS)

Vasectomy and urolithiasis.

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).

Features of cardiac arrest episodes with and without acute myocardial infarction in the Coronary Artery Surgery Study (CASS).

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.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of coronary bypass surgery for 'left main equivalent' coronary disease: the Coronary Artery Surgery Study registry.

Combined proximal left anterior descending and proximal left circumflex, or "left main equivalent" (LMEQ), disease defines a prognostic angiographic high-risk patient population. We assessed the effect of coronary bypass surgery compared with medical therapy in 903 patients with LMEQ disease by stratified life table and Cox regression analysis. The 5 year survival rates of the 639 and 264 patients who received surgical vs medical therapy was 85% vs 55%, respectively (p less than .001). Analysis of patient subsets stratified by age, angina class, right coronary disease, and ejection fraction revealed a significant survival benefit for surgically treated patients in most strata. Cox regression analysis revealed improved survival for surgically treated patients after adjustment for important baseline variables known to influence prognosis. Surgically treated patients had significantly less angina and need for antianginal drugs compared with the medically treated group. When the Coronary Artery Surgery Study randomized and randomizable LMEQ patients were analyzed, coronary bypass surgery improved 5 year survival when preoperative ejection fraction was under 0.50 but not when ejection fraction was 0.50 or higher. Thus coronary bypass surgery prolongs and improves quality of life (as defined by angina status and need for antianginal drugs) in most patients with LMEQ disease but does not appear to improve 5 year survival in a small subset of LMEQ patients who are asymptomatic after myocardial infarction or who have mild chronic stable angina and are under age 65 with well-preserved left ventricular function.

The effect of medical and surgical treatment on subsequent sudden cardiac death in patients with coronary artery disease: a report from the Coronary Artery Surgery Study.

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.

Effect of cigarette smoking on survival of patients with angiographically documented coronary artery disease. Report from the CASS registry.

Through a multicenter registry of patients in the Coronary Artery Surgery Study, we prospectively evaluated morbidity and mortality in 4,165 smokers with angiographically proved coronary artery disease, 2,675 of whom continued to smoke and 1,490 of whom quit. At five years, mortality (adjusted by Cox analysis for baseline differences) was 22% for those who continued smoking and 15% for quitters. The relative risk (also from the Cox analysis) for mortality in continuers vs quitters was 1.55 (95% confidence interval, 1.29 to 1.85). The adverse effect of smoking mainly took the form of higher frequencies of myocardial infarction--associated death and sudden death: the frequencies of these events during follow-up in continuers vs quitters were 7.9% vs 4.4% for myocardial infarction--associated death and 2.8% vs 1.5% for sudden death. This study supports the recommendation that patients with coronary artery disease should stop smoking.

Coronary artery surgery study (CASS): a randomized trial of coronary bypass surgery. Eight years follow-up and survival in patients with reduced ejection fraction.

Survival data after 8 years of follow-up for all patients and after 7 years for certain subgroups are reported from CASS, a randomized trial of surgical or medical treatment assignment in patients with coronary artery disease who have less than severe angina or are asymptomatic after myocardial infarction. After 8 years, survival curves are not significantly different between medical and surgical groups; 87% of patients assigned to surgical and 84% of those assigned to medical treatment are alive. A significant advantage favoring surgical assignment was observed in patients with three-vessel disease and reduced ejection fractions (less than 0.5. but greater than 0.35); after 7 years of follow-up, 88% of the patients in the surgical group and 65% of those in the medical group are alive (p = .009). Survival curves for patients with normal resting ejection fractions are identical after 7 years. We conclude that the CASS trial reveals a significant advantage favoring surgical therapy in patients with three-vessel disease and impaired ventricular function who are randomly assigned to treatment.

Epidemiology of congestive heart failure.

The incidence of congestive heart failure (CHF) is influenced by a variety of factors, including availability of medical care, socioeconomic status, geography, nutrition and race. The etiology of CHF in China, England, Botswana and Sweden will be examined and compared with prospective findings from Boston and Detroit. Because the therapy used in the treatment of CHF varies with the underlying causes, which may be as diverse as rheumatic fever, systemic hypertension and viral infection, the importance of fully determining its pathogenesis is emphasized.

A randomized trial of coronary artery bypass surgery. Survival of patients with a low ejection fraction.

The Coronary Artery Surgery Study (CASS) was designed to compare medical and surgical treatment of selected patients with chronic, stable coronary artery disease. This report concerns a subset of patients with reduced ventricular function. Of 780 patients randomly assigned to medical or surgical treatment, 160 had ejection fractions above 0.34 but below 0.50 at base line and have been followed for an average of seven years. Eighty-two patients were assigned to medical therapy, and 78 to surgery; the two groups were comparable at base line with regard to prognostically important variables. At seven years, 84 per cent of patients in the surgical group were alive, as compared with 70 per cent of the medical group (P = 0.01). Nearly half the patients with impaired ventricular function had triple-vessel disease at entry; at seven years, observed survival in this group was 88 and 65 per cent for those assigned to surgical and medical treatment, respectively (P = 0.009). Survival of patients with single-vessel or double-vessel disease was similar in the two treatment groups. We conclude that patients with triple-vessel disease and ejection fractions higher than 0.34 but lower than 0.50 appear to have improved seven-year survival with elective bypass surgery.