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

Masunori Matsuzaki, Toshio Ogihara, Seiji Umemoto, Hiromi Rakugi, Hiroaki Matsuoka, Kazuyuki Shimada, Keishi Abe, Norihiro Suzuki, Tanenao Eto, Jitsuo Higaki, Sadayoshi Ito, Akira Kamiya, Kenjiro Kikuchi, Hiromichi Suzuki, Chuwa Tei, Yasuo Ohashi, Takao Saruta

Research output: Contribution to journalArticlepeer-review

87 Citations (Scopus)


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<140/90mmHg) with calcium channel blocker (CCB) benidipine 4mg/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.

Original languageEnglish
Pages (from-to)1649-1659
Number of pages11
JournalJournal of hypertension
Issue number8
Publication statusPublished - 2011 Aug
Externally publishedYes


  • adrenergic β-antagonists
  • angiotensin antagonists
  • antihypertensive therapy/diuretics
  • calcium channel blockers
  • clinical trials
  • combination
  • drug therapy

ASJC Scopus subject areas

  • Internal Medicine
  • Physiology
  • Cardiology and Cardiovascular Medicine


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