title: Efficacy and safety of verapamil in patients with angina pectoris after 1 year of continuous, high-dose therapy.
abstract: The long-term efficacy and safety of high-dose verapamil therapy (480 mg/day) was assessed in 26 patients with chronic stable angina pectoris during a 3-phase protocol: Phase 1--an initial, 6-week placebo-controlled, double-blind crossover assessment; Phase 2--an open label, 1-year follow-up; and Phase 3--a final drug withdrawal and rechallenge 10-week study. Three patients withdrew during Phase 2 (1 had hepatitis and 2 underwent coronary bypass surgery). Adverse effects during Phase 2 were mild, consisting of constipation (6 patients) and prolongation of the P-R interval (5 patients); however, no patient required alteration of the 480 mg/day dosage. At the end of Phase 2, 10 patients underwent the Phase 3 study, commencing with a 2-week period in which verapamil was either tapered gradually or abruptly discontinued. This was followed by an 8-week double-blind, placebo-controlled crossover rechallenge study with verapamil. The clinical and exercise responses to verapamil compared with placebo were similar during the Phase 3 protocol and the initial Phase 1 study (treadmill time increased by 55% and anginal attacks per week decreased by 63% during Phase 3, compared with a 28% increase and a 42% decrease, respectively, during Phase 1, p = not significant [NS]). Withdrawal of verapamil produced a similar return of anginal symptoms whether the drug was abruptly discontinued or its administration tapered. No patient had unstable angina pectoris or acute myocardial infarction. These investigations demonstrate that verapamil is safe and effective when evaluated after 1 year of continuous therapy using a dosage of 480 mg/day. There is no evidence of drug tachyphylaxis, nor does verapamil appear to cause an abrupt withdrawal syndrome in patients with chronic stable angina pectoris.
mesh_terms: D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004311:Double-Blind Method; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D005082:Physical Exertion / Q000187:drug effects; D014700:Verapamil / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use
chemical_list: D014700:Verapamil