Angiotensin II receptor blocker-based therapy in Japanese elderly, high-risk, hypertensive patients

Am J Med. 2012 Oct;125(10):981-90. doi: 10.1016/j.amjmed.2011.12.010. Epub 2012 Apr 14.

Abstract

Background: It is unknown whether high-dose angiotensin II receptor blocker therapy or angiotensin II receptor blocker + calcium channel blocker combination therapy is better in elderly hypertensive patients with high cardiovascular risk. The objective of the study was to compare the efficacy of these treatments in elderly, high-risk Japanese hypertensive patients.

Methods: The OlmeSartan and Calcium Antagonists Randomized (OSCAR) study was a multicenter, prospective, randomized, open-label, blinded-end point study of 1164 hypertensive patients aged 65 to 84 years with type 2 diabetes or cardiovascular disease. Patients with uncontrolled hypertension during treatment with olmesartan 20 mg/d were randomly assigned to receive 40 mg/d olmesartan (high-dose angiotensin II receptor blocker) or a calcium channel blocker + 20 mg/d olmesartan (angiotensin II receptor blocker + calcium channel blocker). The primary end point was a composite of cardiovascular events and noncardiovascular death.

Results: During a 3-year follow-up, blood pressure was significantly lower in the angiotensin II receptor blocker + calcium channel blocker group than in the high-dose angiotensin II receptor blocker group. Mean blood pressure at 36 months was 135.0/74.3 mm Hg in the high-dose angiotensin II receptor blocker group and 132.6/72.6 mm Hg in the angiotensin II receptor blocker + calcium channel blocker group. More primary end points occurred in the high-dose angiotensin II receptor blocker group than in the angiotensin II receptor blocker + calcium channel blocker group (58 vs 48 events, hazard ratio [HR], 1.31, 95% confidence interval, 0.89-1.92; P=.17). In patients with cardiovascular disease at baseline, more primary events occurred in the high-dose angiotensin II receptor blocker group (HR, 1.63, P=.03); in contrast, fewer events were observed in the subgroup without cardiovascular disease (HR, 0.52, P=.14). This treatment-by-subgroup interaction was significant (P=.02).

Conclusion: The angiotensin II receptor blocker and calcium channel blocker combination lowered blood pressure more than the high-dose angiotensin II receptor blocker and reduced the incidence of primary end points more than the high-dose angiotensin II receptor blocker in patients with cardiovascular disease. The addition of a second antihypertensive agent is more effective at lowering blood pressure than simply doubling the dose of an existing agent.

Trial registration: ClinicalTrials.gov NCT00134160.

Publication types

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

MeSH terms

  • Aged
  • Aged, 80 and over
  • Amlodipine / therapeutic use*
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Azetidinecarboxylic Acid / analogs & derivatives*
  • Azetidinecarboxylic Acid / therapeutic use
  • Calcium Channel Blockers / therapeutic use*
  • Cardiovascular Diseases / complications
  • Cardiovascular Diseases / drug therapy
  • Cardiovascular Diseases / mortality
  • Cardiovascular Diseases / prevention & control
  • Diabetes Mellitus, Type 2 / complications
  • Dihydropyridines / therapeutic use*
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Humans
  • Hypertension / complications
  • Hypertension / drug therapy*
  • Hypertension / mortality
  • Imidazoles / therapeutic use*
  • Japan
  • Male
  • Prospective Studies
  • Single-Blind Method
  • Survival Analysis
  • Tetrazoles / therapeutic use*
  • Treatment Outcome

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Calcium Channel Blockers
  • Dihydropyridines
  • Imidazoles
  • Tetrazoles
  • Amlodipine
  • Azetidinecarboxylic Acid
  • olmesartan
  • azelnidipine

Associated data

  • ClinicalTrials.gov/NCT00134160