Martial G. Bourassa

Comparison of coronary bypass surgery with angioplasty in patients with multivessel disease. The Bypass Angioplasty Revascularization Investigation (BARI) Investigators.

BACKGROUND Coronary-artery bypass grafting (CABG) and percutaneous transluminal coronary angioplasty (PTCA) are alternative methods of revascularization in patients with coronary artery disease. We tested the hypothesis that in selected patients with multivessel disease suitable for treatment with either procedure, an initial strategy of PTCA does not result in a poorer five-year clinical outcome than CABG. METHODS Patients with multivessel disease were randomly assigned to an initial treatment strategy of CABG (n = 914) or PTCA (n = 915) and were followed for an average of 5.4 years. Analysis of outcome events was performed according to the intention to treat. RESULTS The respective in-hospital event rates for CABG and PTCA were 1.3 percent and 1.1 percent for mortality, 4.6 percent and 2.1 percent for Q-wave myocardial infarction (P < 0.01), and 0.8 percent and 0.2 percent for stroke. The five-year survival rate was 89.3 percent for those assigned to CABG and 86.3 percent for those assigned to PTCA (P = 0.19; 95 percent confidence interval of the difference in survival, -0.2 percent to 6.0 percent). The respective five-year survival rates free from Q-wave myocardial infarction were 80.4 percent and 78.7 percent. By five years after study entry, 8 percent of the patients assigned to CABG had undergone additional revascularization procedures, as compared with 54 percent of those assigned to PTCA; 69 percent of those assigned to PTCA did not subsequently undergo CABG. Among diabetic patients who were being treated with insulin or oral hypoglycemic agents at base line, a subgroup not specified by the protocol, five-year survival was 80.6 percent for the CABG group as compared with 65.5 percent for the PTCA group (P = 0.003). CONCLUSIONS As compared with CABG, an initial strategy of PTCA did not significantly compromise five-year survival in patients with multivessel disease, although subsequent revascularization was required more often with this strategy. For treated diabetics, five-year survival was significantly better after CABG than after PTCA.

Rhythm control versus rate control for atrial fibrillation and heart failure.

BACKGROUND It is common practice to restore and maintain sinus rhythm in patients with atrial fibrillation and heart failure. This approach is based in part on data indicating that atrial fibrillation is a predictor of death in patients with heart failure and suggesting that the suppression of atrial fibrillation may favorably affect the outcome. However, the benefits and risks of this approach have not been adequately studied. METHODS We conducted a multicenter, randomized trial comparing the maintenance of sinus rhythm (rhythm control) with control of the ventricular rate (rate control) in patients with a left ventricular ejection fraction of 35% or less, symptoms of congestive heart failure, and a history of atrial fibrillation. The primary outcome was the time to death from cardiovascular causes. RESULTS A total of 1376 patients were enrolled (682 in the rhythm-control group and 694 in the rate-control group) and were followed for a mean of 37 months. Of these patients, 182 (27%) in the rhythm-control group died from cardiovascular causes, as compared with 175 (25%) in the rate-control group (hazard ratio in the rhythm-control group, 1.06; 95% confidence interval, 0.86 to 1.30; P=0.59 by the log-rank test). Secondary outcomes were similar in the two groups, including death from any cause (32% in the rhythm-control group and 33% in the rate-control group), stroke (3% and 4%, respectively), worsening heart failure (28% and 31%), and the composite of death from cardiovascular causes, stroke, or worsening heart failure (43% and 46%). There were also no significant differences favoring either strategy in any predefined subgroup. CONCLUSIONS In patients with atrial fibrillation and congestive heart failure, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared with a rate-control strategy. (ClinicalTrials.gov number, NCT00597077.)

Percutaneous transluminal coronary angioplasty in 1985-1986 and 1977-1981. The National Heart, Lung, and Blood Institute Registry

In August 1985, the Percutaneous Transluminal Coronary Angioplasty Registry of the National Heart, Lung, and Blood Institute reopened at its previous sites to document changes in angioplasty strategy and outcome. The new registry entered 1802 consecutive patients who had not had a myocardial infarction in the 10 days before angioplasty. Patient selection, technical outcome, and short-term major complications were compared with those of the 1977 to 1981 registry cohort. The new-registry patients were older and had a significantly higher proportion of multivessel disease (53 vs. 25 percent, P less than 0.001), poor left ventricular function (19 vs. 8 percent, P less than 0.001), previous myocardial infarction (37 vs. 21 percent, P less than 0.001), and previous coronary bypass surgery (13 vs. 9 percent, P less than 0.01). The new-registry cohort also had more complex coronary lesions, and angioplasty attempts in these patients involved more multivessel procedures. Despite these differences, the in-hospital outcome in the new cohort was better. Angiographic success rates according to lesion increased from 67 to 88 percent (P less than 0.001), and overall success rates (measured as a reduction of at least 20 percent in all lesions attempted, without death, myocardial infarction, or coronary bypass surgery) increased from 61 to 78 percent (P less than 0.001). In-hospital mortality for the new cohort was 1 percent, and the nonfatal myocardial infarction rate was 4.3 percent. Both rates are similar to those for the old registry. The long-term efficacy of current angioplasty remains to be determined.

Aspirin and dipyridamole in the prevention of restenosis after percutaneous transluminal coronary angioplasty.

To examine the role of antiplatelet therapy in the prevention of arterial restenosis after percutaneous transluminal coronary angioplasty (PTCA), we conducted a randomized, double-blind, placebo-controlled study in 376 patients. The active treatment consisted of an oral aspirin-dipyridamole combination (330 mg-75 mg) given three times daily, beginning 24 hours before PTCA. Eight hours before PTCA, the oral dipyridamole was replaced with intravenous dipyridamole at a dosage of 10 mg per hour for 24 hours, and oral aspirin was continued. Sixteen hours after PTCA, the initial combination was reinstituted. Treatment was continued in patients with a successfully dilated vessel until follow-up angiography four to seven months after PTCA--or earlier, if symptoms dictated. Of 249 patients who underwent follow-up angiography, 37.7 percent of patients receiving the active drug had restenosis in at least one segment, as compared with 38.6 percent of patients taking placebo (P not significant). The number of stenotic segments was virtually the same in the two groups. Among the 376 randomized patients, there were 16 periprocedural Q-wave myocardial infarctions--13 in the placebo group and 3 in the active-drug group (6.9 percent vs. 1.6 percent, P = 0.0113). Although the use of this antiplatelet regimen before and after PTCA did not reduce the six-month rate of restenosis after successful coronary angioplasty, it markedly reduced the incidence of transmural myocardial infarction during or soon after PTCA. Thus, the short-term use of antiplatelet agents in relation to PTCA can be recommended.

Probucol and Multivitamins in the Prevention of Restenosis after Coronary Angioplasty

BACKGROUND Oxidizing metabolites generated at the site of coronary angioplasty can induce chain reactions that may lead to restenosis. Antioxidants may counter oxidative stress and modify neointimal formation and vascular remodeling. Experimental data and small clinical studies have suggested that antioxidants may prevent restenosis after angioplasty. In a double-blind, randomized trial, we studied whether drugs with antioxidant properties decrease the incidence and severity of restenosis after angioplasty. METHODS One month before angioplasty, 317 patients were randomly assigned to receive one of four treatments: placebo, probucol (500 mg), multivitamins (30,000 IU of beta carotene, 500 mg of vitamin C, and 700 IU of vitamin E), or both probucol and multivitamins-all given twice daily. Patients were treated for four weeks before and six months after angioplasty. Patients received an extra 1000 mg of probucol, 2000 IU of vitamin E, both probucol and vitamin E, or placebo 12 hours before angioplasty, according to their treatment assignments. Base-line and follow-up angiograms were interpreted by blinded investigators using a quantitative approach. RESULTS The mean (+/-SD) reduction in luminal diameter six months after angioplasty was 0.12 +/- 0.41 mm in the probucol group, 0.22 +/- 0.46 mm in the combined-treatment group, 0.33 +/- 0.51 in the multivitamin group, and 0.38 +/- 0.50 mm in the placebo group (P = 0.006 for those receiving vs. those not receiving probucol, and P = 0.70 for those receiving vs. those not receiving vitamins. Restenosis rates per segment were 20.7 percent in the probucol group, 28.9 percent in the combined-treatment group, 40.3 percent in the multivitamin group, and 38.9 percent in the placebo group (P = 0.003 for probucol vs. no probucol). The rates of repeat angioplasty were 11.2 percent. 16.2 percent, 24.4 percent, and 26.6 percent, respectively (P = 0.009 for probucol vs. no probucol). CONCLUSIONS The antioxidant probucol is effective in reducing the rate of restenosis after balloon coronary angioplasty.

Effect of Enalapril On Myocardial-infarction and Unstable Angina in Patients With Low Ejection Fractions

An association between raised renin levels and myocardial infarction has been reported. We studied the effects of enalapril, an angiotensin-converting enzyme (ACE) inhibitor, on the development of myocardial infarction and unstable angina in 6797 patients with ejection fractions < or = 0.35 enrolled into the two Studies of Left Ventricular Dysfunction (SOLVD) trials. Patients were randomly assigned to placebo (n = 3401) or enalapril (n = 3396) at doses of 2.5-20 mg per day in two concurrent double-blind trials with the same protocol. Patients with heart failure entered the treatment trial (n = 2569) and those without heart failure entered the prevention trial (n = 4228). Follow-up averaged 40 months. In each trial there were significant reductions in the number of patients developing myocardial infarction (treatment trial: 158 placebo vs 127 enalapril, p < 0.02; prevention trial: 204 vs 161 p < 0.01) or unstable angina (240 vs 187 p < 0.001; 355 vs 312, p < 0.05). Combined, there were 362 placebo group patients with myocardial infarction compared with 288 in the enalapril group (risk reduction 23%, 95% CI 11-34%; p < 0.001). 595 placebo group patients developed unstable angina compared with 499 in the enalapril group (risk reduction 20%, 95% CI 9-29%, p < 0.001). There was also a reduction in cardiac deaths (711 placebo, 615 enalapril; p < 0.003), so that the reduction in the combined endpoint of deaths, myocardial infarction, and unstable angina was highly significant (20% risk reduction, 95% CI 14-26%; p < 0.0001). Enalapril treatment significantly reduced myocardial infarction, unstable angina, and cardiac mortality in patients with low ejection fractions.

Social support, depression, and mortality during the first year after myocardial infarction

BACKGROUND We previously reported that depression after myocardial infarction (MI) increases the long-term risk of cardiac mortality. Other research suggests that social support may also influence prognosis. This article examines the interrelationships between baseline depression and social support in terms of cardiac prognosis and changes in depression symptoms over the first post-MI year. METHODS AND RESULTS For this study, 887 patients completed the Beck Depression Inventory (BDI) and the Perceived Social Support Scale (PSSS) at about 7 days after MI. Some 32% had BDIs > or =10, indicating mild to moderate depression. One-year survival status was determined for all patients. Follow-up interviews, including the BDI, were conducted with 89% of survivors. There were 39 deaths (35 cardiac). Elevated BDI scores were related to cardiac mortality (P=0.0006), but PSSS scores and other measures of social support were not. There was a significant interaction between depression and the PSSS (P=0. 016). The relationship between depression and cardiac mortality decreased with increasing support. Furthermore, residual change score analysis revealed that among 1-year survivors who had been depressed at baseline, higher baseline social support was related to more improvement in depression symptoms than expected. CONCLUSIONS Post-MI depression is a predictor of 1-year cardiac mortality, but social support is not directly related to survival. However, very high levels of support appear to buffer the impact of depression on mortality. Furthermore, high levels of support predict improvements in depression symptoms over the first post-MI year in depressed patients. High levels of support may protect patients from the negative prognostic consequences of depression because of improvements in depression symptoms.

Enalapril Decreases the Incidence of Atrial Fibrillation in Patients With Left Ventricular Dysfunction Insight From the Studies Of Left Ventricular Dysfunction (SOLVD) Trials

Background Atrial fibrillation (AF) is frequently encountered in patients with heart failure (HF) and is also a predictor of morbidity and mortality in this population. Recent experimental studies have shown electrical and structural atrial remodeling with increased fibrosis in animals with HF and have suggested a preventive effect of ACE inhibitors (ACEi) on the development of AF. To verify the hypothesis that ACEi prevent the development of AF in patients with HF, we conducted a retrospective analysis of the patients from the Montreal Heart Institute (MHI) included in the Studies Of Left Ventricular Dysfunction (SOLVD). Methods and Results Clinical charts were reviewed and serial ECGs interpreted by a single cardiologist blinded to drug allocation. Patients with AF or flutter on the baseline ECG were excluded. Baseline characteristics were obtained from the SOLVD databases. The mean follow‐up was 2.9±1.0 years. Of the 391 patients randomly assigned at MHI, 374 were in sinus rhythm at the time of random assignment, with 186 taking enalapril and 188 taking placebo. Baseline characteristics were similar in the two groups except for a higher incidence of previous myocardial infarction in the enalapril group. Fifty‐five patients had AF during the follow‐up: 10 (5.4%) in the enalapril group and 45 (24%) in the placebo group (P<0.0001). By Cox multivariate analysis, enalapril was the most powerful predictor for risk reduction of AF (hazard ratio, 0.22; 95% CI, 0.11 to 0.44; P<0.0001). Conclusions Treatment with the ACEi enalapril markedly reduces the risk of development of atrial fibrillation in patients with left ventricular dysfunction. (Circulation. 2003;107:2926‐2931.)

Asymptomatic Cardiac Ischemia Pilot (ACIP) Study Improvement of Cardiac Ischemia at 1 Year After PTCA and CABG

BACKGROUND Cardiac ischemia on the ambulatory ECG (AECG) and/or on the exercise treadmill test (ETT) is associated with an increased risk of adverse outcome. Myocardial revascularization more often suppresses cardiac ischemia than does medical management alone. However, few studies have compared the effects of percutaneous transluminal coronary angioplasty (PTCA) with those of coronary artery bypass grafting (CABG) on cardiac ischemia and clinical outcome. METHODS AND RESULTS A total of 558 patients were randomly assigned to one of three treatment strategies in the Asymptomatic Cardiac Ischemia Pilot (ACIP) study: angina-guided medical strategy (n = 184), ischemia-guided medical strategy (n = 182), or revascularization (n = 192). In patients assigned to revascularization, the choice of the procedure, PTCA or CABG, was made by the clinical unit staff and patient based on a coronary angiogram usually performed within 2 months of enrollment. CABG was selected in 78 patients and PTCA in 92 patients. At 12 weeks, ischemia on the AECG was suppressed in 70% of CABG patients versus 46% of PTCA patients (P = .002). Ischemia on the ETT was no longer present in 46% versus 23% of the patients, respectively (P = .005). Angina, within 4 weeks of the follow-up visit, was absent in 90% versus 68%, respectively (P = .001). These clinical variables remained improved in both groups at 1 year. Clinical events (myocardial infarction or repeat revascularization) occurred in 1 CABG patient versus 7 PTCA patients at 12 weeks, and in 1 versus 16 patients, respectively, at 12 months (P < .001). CONCLUSIONS Ischemia on the AECG and ETT and angina were relieved in many patients after both procedures; however, CABG was superior to PTCA, and it was associated with a lower incidence of clinical events at 1 year. These results suggest that more complete revascularization relates to better clinical outcome. However, a large trial is needed to confirm these results.

The relation of risk factors to the development of atherosclerosis in saphenous-vein bypass grafts and the progression of disease in the native circulation: a study 10 years after aortocoronary bypass surgery

We examined 82 patients 10 years after saphenous-vein aortocoronary bypass surgery to determine their angiographic status and to relate those findings to the risk factors for coronary-artery disease. Of 132 grafts shown to be patent 1 year after surgery, only 50 were unaffected at 10 years. The remainder were narrowed (43) or occluded (39). Disease progression in coronary arteries without grafts was also frequent, both in vessels that were normal (15 of 32) and in those with minor stenosis (25 of 53). New lesions did not develop in 15 patients, whereas they did in 67--in the grafts, the native vessels, or both. There was no significant difference between the two groups in the incidence of hypertension, diabetes, or smoking, whereas plasma levels of very-low-density lipoproteins (VLDLs) and low-density lipoproteins (LDLs) were higher, and high-density lipoprotein (HDL) levels were lower in those with new disease than in those without. Univariate analysis showed that plasma cholesterol and triglyceride levels were significantly higher at the time of surgery and at the 10-year examination in those with new lesions. Multivariate analysis indicated that among the lipoprotein indexes, levels of HDL cholesterol and plasma LDL apoprotein B best distinguished the two groups. The findings indicate that atherosclerosis in these patients was a progressive disease, frequently affecting both the grafts and the native vessels, and that the course of such disease may be related to the plasma lipoprotein levels.