The risk of myocardial infarction associated with antihypertensive drug therapies

JAMA. 1995 Aug;274(8):620-5.


Objective: To assess the association between first myocardial infarction and the use of antihypertensive agents.

Design and setting: We conducted a population-based case-control study among enrollees of the Group Health Cooperative of Puget Sound (GHC).

Patients and methods: Cases were hypertensive patients who sustained a first fatal or nonfatal myocardial infarction from 1986 through 1993 among women and from 1989 through 1993 among men. Controls were a stratified random sample of hypertensive GHC enrollees, frequency matched to the cases on age, sex, and calendar year. All 623 cases and 2032 controls had pharmacologically treated hypertension. Data collection included a review of the ambulatory medical record a brief telephone interview of consenting survivors. Antihypertensive therapy was assessed using the GHC's computerized pharmacy database.

Results: The first analysis included only the 335 cases and 1395 controls initially free of cardiovascular disease. Compared with users of diuretics alone, the adjusted risk ratio of myocardial infarction was increased by about 60% among users of calcium channel blockers with or without diuretic (risk ratio = 1.62%; 95% confidence interval [Cl], 1.11 to 2.34; P = .01). The second analysis was restricted to 384 cases and 1108 controls who were taking either a calcium channel blocker or a beta-blocker. Among these subjects, the use of calcium channel blockers compared with beta-blockers was associated with about a 60% increase in the adjusted risk of myocardial infarction (risk ratio = 1.57; 95% Cl, 1.21 to 2.04; P < .001). While high doses of beta-blockers were associated with a decreased risk of myocardial infarction (trend P = .04), high doses of calcium channel blockers were associated with an increased risk (trend P < .01).

Conclusions: In this study of hypertensive patients, the use of short-acting calcium channel blockers, especially in high doses, was associated with an increased risk of myocardial infarction. Ongoing large-scale clinical trials will assess the effect of various antihypertensive therapies, including calcium channel blockers, on several important cardiovascular end points. Until these results are available, the findings of this study support the current guidelines from the Joint National Committee on the Detection, Evaluation and Treatment of High Blood Pressure that recommend diuretics and beta-blockers as first-line agents unless contraindicated, unacceptable, or not tolerated.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adrenergic beta-Antagonists / adverse effects
  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Antihypertensive Agents* / administration & dosage
  • Antihypertensive Agents* / adverse effects
  • Antihypertensive Agents* / therapeutic use
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Case-Control Studies
  • Confounding Factors, Epidemiologic
  • Diuretics / adverse effects
  • Diuretics / therapeutic use
  • Dose-Response Relationship, Drug
  • Female
  • Humans
  • Hypertension / drug therapy
  • Hypertension / physiopathology
  • Incidence
  • Linear Models
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology*
  • Myocardial Infarction / etiology
  • Risk Factors
  • Survivors


  • Adrenergic beta-Antagonists
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics