Prevention of cardiovascular events with calcium channel blocker-based combination therapies in patients with hypertension: a randomized controlled trial

J Hypertens. 2011 Aug;29(8):1649-59. doi: 10.1097/HJH.0b013e328348345d.

Abstract

Objectives: Current guidelines recommend the use of multiple medications for hypertension. The present study was aimed at determining which combination was optimal to prevent cardiovascular events.

Methods: We conducted a prospective, randomized, open-label, blinded-endpoint trial. Hypertensive outpatients aged between 40 and 85 years who did not achieve target blood pressure (BP<140/90 mmHg) with calcium channel blocker (CCB) benidipine 4 mg/day were randomly assigned to receive angiotensin receptor blocker (ARB), β-blocker, or thiazide diuretic in addition to benidipine.

Results: Among a total of 3501 patients (1167, benidipine-ARB; 1166, benidipine-β-blocker; and 1168, benidipine-thiazide), 3293 patients (1110, 1089, and 1094, respectively) who received each combination treatment were included in the analysis. Median follow-up was 3.61 years. At the end of the treatment, 64.1, 66.9, and 66.0% of patients in the benidipine-ARB, benidipine-β-blocker, and benidipine-thiazide groups achieved target BP, respectively. The cardiovascular composite endpoint occurred in 41 (3.7%), 48 (4.4%), and 32 (2.9%) patients, respectively: the hazard ratio was 1.26 in the benidipine-ARB (P = 0.3505) and 1.54 in the benidipine-β-blocker (P = 0.0567) groups compared with the benidipine-thiazide group. The secondary analyses revealed that benidipine and thiazide diuretic significantly reduced the incidence of fatal or nonfatal strokes (P = 0.0109) and benidipine and ARB significantly reduced new-onset diabetes (P = 0.0240) compared with benidipine and β-blocker. All trial treatments were safe and well tolerated.

Conclusion: CCB combined with ARB, β-blocker, or thiazide diuretic was similarly effective for the prevention of cardiovascular events and the achievement of target BP.

Trial registration: ClinicalTrials.gov NCT00135551.

Publication types

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

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use*
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / therapeutic use*
  • Calcium Channel Blockers / therapeutic use*
  • Dihydropyridines / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Incidence
  • Japan
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Prospective Studies
  • Risk Factors
  • Single-Blind Method
  • Sodium Chloride Symporter Inhibitors / therapeutic use*
  • Stroke / epidemiology
  • Stroke / prevention & control*
  • Treatment Outcome

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin Receptor Antagonists
  • Calcium Channel Blockers
  • Dihydropyridines
  • Sodium Chloride Symporter Inhibitors
  • benidipine

Associated data

  • ClinicalTrials.gov/NCT00135551