Verapamil-sustained release-based treatment strategy is equivalent to atenolol-based treatment strategy at reducing cardiovascular events in patients with prior myocardial infarction: an INternational VErapamil SR-Trandolapril (INVEST) substudy.

BACKGROUND: In patients with prior myocardial infarction (MI), beta-blockers reduce mortality by 23% to 40%. However, despite this favorable effect, adverse effects limit compliance to this medication. The purpose of the study was to compare a beta-blocker-based strategy with a heart rate-lowering calcium antagonists-based strategy in patients with prior MI. METHODS: We evaluated 7,218 patients with prior MI enrolled in the INternational VErapamil SR-Trandolapril (INVEST) substudy randomized to verapamil-sustained release (SR)- or atenolol-based strategies. Primary outcome was time to first occurrence of death (all-cause), nonfatal MI, or nonfatal stroke. Secondary outcomes included death, total MI (fatal and nonfatal), and total stroke (fatal and nonfatal) considered separately. RESULTS: During the 2.8 +/- 1.0 years of follow-up, patients assigned to the verapamil-SR-based and atenolol-based strategies had comparable blood pressure control, and the incidence of the primary outcome was equivalent. There was no difference between the 2 strategies for the outcomes of either death or total MI. However, more patients reported excellent/good well-being (82.3% vs 78.0%, P = .02) at 24 months with a trend toward less incidence of angina pectoris (12.0% vs 14.3%, adjusted P = .07), nonfatal stroke (1.4% vs 2.0%; P = .06), and total stroke (2.0% vs 2.5%, P = .18) in the verapamil-SR-based strategy group. CONCLUSIONS: In hypertensive patients with prior MI, a verapamil-SR-based strategy was equivalent to a beta-blocker-based strategy for blood pressure control and prevention of cardiovascular events, with greater subjective feeling of well-being and a trend toward lower incidence of angina pectoris and stroke in the verapamil-SR-based group.

Antihypertensive properties of a high-dose combination of trandolapril and verapamil-SR.

The superior diastolic blood pressure reduction (BP) of high-dose combination therapy with trandolapril (Tr) and verapamil-SR (Ve) compared with monotherapy has previously been reported. Guideline changes, placing greater emphasis on systolic BP, prompted a re-evaluation of TV-51 and an assessment of a subset of patients from the INternational VErapamil-SR Trandolapril STudy (INVEST). The objective of this analysis was to determine if the short-term antihypertensive effects of high-dose Tr+Ve (Tr/Ve study) could be confirmed in a sample of higher-risk INVEST patients with longer follow-up. The Tr/Ve study was a double-blind, randomized, parallel-group, placebo-controlled trial to evaluate the antihypertensive effects of trandolapril and verapamil-SR alone or in combination in 631 patients randomized to placebo, 4 mg trandolapril, 240 mg verapamil-SR or 4 mg/240 mg Tr+Ve combination for 6 weeks; 581 INVEST patients were selected for comparison with 24-month BP data, 90% use of trandolapril and verapamil-SR combination therapy and no triple therapy. Tr+Ve combination treatment achieved significantly greater systolic and diastolic BP reduction versus monotherapy. The BP-lowering effects of high-dose Tr+Ve achieved during short-term treatment were confirmed in INVEST during longer follow-up. Despite differences in the risk profiles of previously studied patients and INVEST patients, the antihypertensive effects of Ve+Tr were similar.