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

Am Heart J. 2008 Aug;156(2):241-7. doi: 10.1016/j.ahj.2008.02.023.


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.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use*
  • Aged
  • Angina Pectoris / prevention & control
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Atenolol / adverse effects
  • Atenolol / therapeutic use*
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use*
  • Delayed-Action Preparations
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / drug therapy*
  • Indoles / therapeutic use
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy*
  • Myocardial Infarction / mortality
  • Myocardial Infarction / prevention & control
  • Proportional Hazards Models
  • Risk
  • Single-Blind Method
  • Stroke / epidemiology
  • Stroke / mortality
  • Stroke / prevention & control*
  • Verapamil / adverse effects
  • Verapamil / therapeutic use*


  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Calcium Channel Blockers
  • Delayed-Action Preparations
  • Indoles
  • trandolapril
  • Atenolol
  • Verapamil