Comparative effects of propranolol and verapamil alone and in combination on left ventricular function and volumes in patients with chronic exertional angina: a double-blind, placebo-controlled, randomized, crossover study with radionuclide ventriculography.

Abstract

With the use of equilibrium radionuclide ventriculography the effects on left ventricular (LV) function of 160 mg oral propranolol daily and 360 mg verapamil daily alone and in combination were compared in 18 patients with chronic exertional angina. A randomized, double-blind, placebocontrolled, crossover protocol was used. The reduction in exercise rate-pressure product induced by the combination (1 18 ± 28 mm Hg/min) was significantly greater (p < .05) than that by propranolol (135 + 27 mm Hg/min) or verapamil alone (163 ± 28 mm Hg/min). In patients at rest, neither single nor combined therapy altered global or regional left ventricular ejection fractions (EFs). Verapamil, but not propranolol, increased (p < .05) cardiac volumes of resting subjects; used in combination, no further increase in LV volume occurred. With placebo, exercise global EF did not decrease from the level at rest and therefore no drug effect could be demonstrated for this parameter of LV function. By an evaluation of normalized regional EF measurements the combination was shown to reduce exerciseinduced hypokinesis (placebo 52 ± 20%, combination 61 + 23%; p < .01). No significant improvement was noted with propranolol or verapamil alone; only the combination prevented a significant increase in end-systolic and end-diastolic volumes during exercise. Thus, propranolol and verapamil, used alone in moderate doses, exert no beneficial effect on exercise LV function as measured by EF and volume changes, and resting function deteriorates slightly with verapamil. Compared with single-drug therapy, the combination causes no further change in LV function of resting subjects and improves exercise function. This improvement was most likely due to a reduction in myocardial oxygen demand. Circulation 68, No. 6, 1280No. 6, -1289No. 6, , 1983 COMBINATION THERAPY with /8-adrenergic-receptor antagonists and nitrates is a well-established part of the treatment of chronic exertional angina. Recently, reports have shown that calcium-channel antagonists such as verapamil have antianginal properties comparable to those of propranolol.'-1 Moreover, in selected patients, the combination of propranolol and

Amlodipine reduces myocardial ischaemia during exercise without compromising left ventricular function in patients with silent ischaemia: a randomised, double‐blind, placebo‐controlled study

“…Verapamil and diltiazem have negative inotropic effects and caution should be exercised when treating patients with signs of congestive heart failure. Amlodipine may also possess a certain negative inotropic effect in patients with angina pectoris, when the recommended treatment dose is exaggerated .…”

“…Calcium antagonists are effective in relieving angina pectoris and in reducing electrocardiographic ST‐depressions during exercise tests and during Holter‐monitoring ,, but the effect of calcium antagonists on global LV function during exercise‐induced ischaemia has only been studied in patients with angina pectoris and only a few controlled studies have been conducted. In those studies, verapamil and diltiazem seemed to reduce LV function ,, whereas the dihydropyridine‐like agents have shown inconsistent influence on LVEF ,. The long‐acting calcium antagonist amlodipine is an effective anti‐ischaemic drug, reducing both angina pectoris and silent electrocardiographic ST‐depressions .…”

Pharmacologic and Therapeutic Considerations in Hypertension Therapy With Calcium Channel Blockers: Focus on Verapamil

“…Such drugs include cyclosporine; the antiepileptic carbamazepine; prazosin; lovastatin, atorvastatin, and simvastatin; theophylline; some human immunodeficiency virus protease inhibitors; and quinidine. 57 The combination of verapamil and β-blockade improves myocardial function during exercise more so than either agent alone 58 and may also prove additive in the treatment of hypertension. 56 Verapamil and β-blockers given together carry the risk of added hypotension or nodal inhibition.…”

Micellar liquid chromatographic determination of five antianginals in pharmaceuticals

“…The equilibria between the monoprotonated (BH + ) and non-protonated (B) antianginals (acid-base constants, pK a = 7.7-9.45, see Table 1) take place outside the working pH range of a C18 column (3)(4)(5)(6)(7). For these compounds, the retention was thus the same using mobile phases of SDS at pH 3 and 7.…”

“…If treatment of angina with calcium channel blockers or ␤-blockers alone in monotherapy fails, an association of both can be effective and safe even in the paediatric age [2][3][4][5][6][7][8][9][10][11]. ␤-Blockers diminish the heart rate, resulting in decreased myocardial oxygen demand and increased oxygen delivery to the heart, and also decrease myocardial contractility, thus helping to conserve energy or decrease demand.…”