Comparison of effects on peak oxygen consumption, quality of life, and neurohormones of felodipine and enalapril in patients with congestive heart failure.

Angiotensin-converting enzyme (ACE) inhibition is currently the cornerstone of congestive heart failure (CHF) therapy, but these drugs are not tolerated in up to 20% of patients. For these patients, therapeutic alternatives with comparable efficacy are needed. Felodipine, a vasoselective dihydropyridine calcium antagonist with a slow onset of action and a long plasma half-life, may be such an agent. Therefore, the efficacy and safety of felodipine were examined and compared with enalapril using a double-blind design. We studied 46 patients with a left ventricular ejection fraction < 0.40, peak oxygen consumption < 20 ml.min-1.kg-1, and symptoms of CHF despite therapy with diuretics and digoxin. After 16 weeks of therapy, there were no statistically significant differences in peak oxygen consumption (felodipine +1.6, enalapril +2.5 ml.min-1.kg-1) and exercise tolerance (felodipine +61 seconds, enalapril +64 seconds). Quality-of-life parameters were affected slightly better by felodipine than by enalapril. Plasma norepinephrine decreased by 143 pg.ml-1 with enalapril and by 12 pg.ml-1 with felodipine (p < 0.20 between groups). Both drugs were generally well tolerated. These data suggest that felodipine and enalapril have comparable effects on exercise parameters in patients with CHF. Neurohumoral activation was not observed with either drug.

Usefulness of heart rate variability in predicting drug efficacy (metoprolol vs diltiazem) in patients with stable angina pectoris.

We investigated whether analysis of heart rate (HR) variability may be used to predict the efficacy of drug treatment of myocardial ischemia. In a double-blind, crossover study, 28 patients with stable angina pectoris, proven coronary artery disease, and myocardial ischemia during Holter monitoring received metoprolol controlled-release 200 mg once daily and diltiazem 60 mg 4 times daily. After a placebo run-in phase and after each treatment period, 72-hour Holter recordings were obtained for HR variability and ST-segment analysis. At baseline, the total duration of myocardial ischemia was 11.4 +/- 13.9 minutes (mean +/- SD per 24 hours), and the total number of episodes was 2.2 +/- 2.3. Metoprolol significantly reduced the total duration of ischemia by -8.7 minutes (95% CI -14.5 to -2.8) and the total number of episodes by -1.9 (-2.9 to -0.8) in patients with a low SD of normal-to-normal intervals at baseline (SDNN), using the median value of 50 ms as a cut-off value. In contrast, significant treatment effects were not observed in patients with a high SDNN at baseline. Similar results were obtained using baseline total power or low-frequency power, but not when using baseline heart rate. Diltiazem reduced the total duration of ischemia by -4.9 minutes (-9.7 to -0.1), but not the number of episodes. Moreover, in contrast to metoprolol, efficacy of diltiazem was not related to baseline HR variability. In conclusion, patients with reduced HR variability at baseline responded to treatment with metoprolol.(ABSTRACT TRUNCATED AT 250 WORDS)

Efficacy of metoprolol and diltiazem in treating silent myocardial ischemia.

Recent studies strongly support the prognostic importance of transient silent ischemia. Because patients with silent ischemia are at higher risk of a cardiac event, they are likely to benefit not only from control of symptoms, but also from treatment directed at prevention of ischemia. The efficacy of controlled-release metoprolol 200 mg once daily and diltiazem 60 mg 4 times daily was assessed in a randomized, double-blind, crossover study in 32 patients with proven coronary artery disease, predominantly asymptomatic myocardial ischemia, positive bicycle exercise test results, and > or = 5 minutes of asymptomatic ST-segment depression on a 24-hour screening ambulatory electrocardiogram (ECG). At the beginning and at the end of both 3-week treatment periods, an exercise test was performed and a 72-hour ambulatory ECG was recorded. Both active treatment periods were preceded by a 2-week placebo phase. Both treatments effectively reduced and postponed exercise-induced ST depression and reduced the total ischemic integral on the ambulatory ECG. Only metoprolol significantly reduced the mean number of ischemic episodes (54%, p = 0.0003, vs 31% for diltiazem, p = NS) and the mean duration of ischemia (51%, p = 0.012, vs 27% for diltiazem, p = NS) compared with baseline values. Metoprolol strongly blunted the morning and afternoon peak in the circadian distribution of ischemia, whereas diltiazem did not change the circadian distribution of ischemia at all.