A dose-ranging, placebo-controlled, double-blind trial of nisoldipine in effort angina: Duration and extent of antianginal effects

Maximal treadmill exercise testing at 1, 3 and 8 hours was used to assess the onset, duration and antianginal efficacy of the d1hydropyridine slow channel calciumblocking agent, nisoldipine, in an oral dose range of 5, 10 and 20 mg. A double-blind, randomized, placebo-controlled design was used involving 12 patients with stable effort angina. Exercise tolerance was significantly increased 3 hours after each dose, when the maximal beneficial effect occurred. The improvement was observed as early as 1 hour after the 10 and 20 mg dose, and persisted for 8 hours after the 20 mg dose. At 3 hours, the onset of an exercise-induced ST segment depression of 0.1 mV or greater was increased by 62 (p < 0.05), 75 (p < 0.01) and 117 seconds (p < 0.01) with the 5,10 and 20 mg dose of nisoldipine, respectively, compared with placebo. Similarly, time to onset of angina was significantly increased. The sum of exerciseinduced ST segment depression at peak exercise was significantly decreased (p < 0.05) from 8.7 ± 2.3 to 6.7 ± 1.8 and 6.4 ± 2.0 mm, respectively, after the 10 and 20 mg dose of nisoldipine. The rate-pressure product was significantly greater with nisoldipine than with placebo at the onset of ischemia and at peak exercise (22.8 ± 1.1 versus 20 ± 1.4 × 103 U for the 20 mg dose; p ± 0.01).Thus, nisoldipine is an effective antianginal agent with a rapid onset of action that improves exercise tolerance, increases angina threshold and persists for at least 8 hours after oral dosing

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

AbstractThe 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 ≥70% and an ejection fraction < 0.50, and 2) patients with three vessel coronary artery disease and an ejection fraction < 0.50. In both groups, coronary bypass surgery had a statistically significant beneficial effect on survival (p < 0.05).After a decade of follow-up, the CASS randomizable patients confirm conclusions reached on the basis of the CASS randomized trial

The Anti-Ischemic Mechanism of Action of Ranolazine in Stable Ischemic Heart Disease

OBJECTIVES: The purpose of this explanatory analysis was to investigate the relationship between ST-segment depression and the rate-pressure product (RPP) during exercise to determine whether ranolazine's mechanism of action was related to a reduction in myocardial oxygen demand or preservation of myocardial oxygen supply. BACKGROUND: In patients with stable ischemic heart disease, ranolazine increases exercise duration and reduces maximal ST-segment depression while exerting minimal effects on heart rate and blood pressure, although its mechanism of action during exercise has not been investigated. METHODS: Patients with stable ischemic heart disease (n = 191) were randomly allocated to a 4-period, double-blind, balanced Latin square crossover study to receive placebo, and ranolazine 500, 1,000, and 1,500 mg twice daily (bid) for 1 week each. Exercise treadmill tests were performed at baseline and at the end of each treatment period. The RPP and ST-segment depression were assessed before starting exercise, at each stage of exercise, and at maximal exercise. RESULTS: Compared with placebo, ranolazine produced a dose-dependent reduction in ST-segment depression that became more marked as exercise-induced ischemia became more pronounced, associated with clinically minor decreases in heart rate and blood pressure. At 12-min exercise, the amount of ST-segment depression compared with placebo and controlled for RPP was reduced by 22.3% on ranolazine 500 mg bid (p = 0.137), by 35.4% on 1,000 mg bid (p = 0.005), and by 45.8% on 1,500 mg bid (p < 0.001). CONCLUSIONS: The progressive magnitude of ischemia reduction on ranolazine was proportionally more substantial than the minor reductions in heart rate or RPP, suggesting that ranolazine's beneficial mechanism of action is most likely primarily due to an improvement in regional coronary blood flow in areas of myocardial ischemia

Effects of dalcetrapib in patients with a recent acute coronary syndrome

In observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes

Asymptomatic cardiac ischemia pilot (ACIP) study: Effects of coronary angioplasty and coronary artery bypass graft surgery on recurrent angina and ischemia

ObjectivesThe Asymptomatic Cardiac Ischemia Pilot (ACIP) study showed that revascularization is more effective than medical therapy in suppressing cardiac ischemia at 12 weeks. This report compares the relative efficacy of coronary angioplasty or coronary artery bypass graft surgery in suppressing ambulatory electrocardiographic (ECG) and treadmill exercise cardiac ischemia between 2 and 3 months after revascularization in the ACIP study.BackgroundPrevious studies have shown that coronary angioplasty and bypass surgery relieve angina early after the procedure in a high proportion of selected patients. However, alleviation of ischemia on the ambulatory ECG and treadmill exercise test have not been adequately studied prospectively after revascularization.MethodsIn patients randomly assigned to revascularization in the ACIP study, the choice of coronary angioplasty or bypass surgery was made by the clinical unit staff and the patient.ResultsPatients assigned to bypass surgery (n = 78) had more severe coronary disease (p = 0.001) and more ischemic episodes (p = 0.01) at baseline than those assigned to angioplasty (n = 92). Ambulatory ECG ischemia was no longer present 8 weeks after revascularization (12 weeks after enrollment) in 70% of the bypass surgery group versus 46% of the angioplasty group (p = 0.002). ST segment depression on the exercise ECG was no longer present in 46% of the bypass surgery group versus 23% of the angioplasty group (p = 0.005). Total exercise time in minutes on the treadmill exercise test increased by 2.4 min after bypass surgery and by 1.4 min after angioplasty (p = 0.02). Only 10% of the bypass surgery group versus 32% of the angioplasty group still reported angina in the 4 weeks before the 12-week visit (p = 0.001).ConclusionsAngina and ambulatory ECG ischemia are relieved in a high proportion of patients early after revascularization. However, ischemia can still be induced on the treadmill exercise test, albeit at higher levels of exercise, in many patients. Bypass surgery was superior to coronary angioplasty in suppressing cardiac ischemia despite the finding that patients who underwent bypass surgery had more severe coronary artery disease

The QT interval and risk of incident atrial fibrillation

Abnormal atrial repolarization is important in the development of atrial fibrillation (AF), but no direct measurement is available in clinical medicine