Angiotensin II receptor blocker-based vs. non-angiotensin II receptor blocker-based therapy in patients with angiographically documented coronary artery disease and hypertension: the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease (HIJ-CREATE)

Eur Heart J. 2009 May;30(10):1203-12. doi: 10.1093/eurheartj/ehp101. Epub 2009 Apr 4.

Abstract

Aims: To test whether angiotensin II receptor blockers (ARBs) therapy can reduce the incidence of cardiovascular events compared with non-ARB-based standard pharmacotherapy in coronary artery disease (CAD) patients with hypertension.

Methods and results: Angiographically documented CAD patients with hypertension were randomly assigned to receive either candesartan-based (n= 1024) or non-ARB-based pharmacotherapy including angiotensin-converting enzyme-inhibitors (n = 1025). The primary endpoint was the occurrence of a first major adverse cardiovascular event (MACE). There were 552 primary events during a median follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (hazard ratio, 0.89; 95% confidence interval, 0.76-1.06). No significant differences existed between groups in terms of cardiovascular death (2.7 vs. 2.4%, 1.14; 0.66-1.95), non-fatal myocardial infarction (2.8 vs. 2.5%, 1.12; 0.66-1.88), or heart failure (3.9 vs. 4.3%, 0.91; 0.59-1.40). New-onset diabetes was diagnosed significantly less frequently with candesartan than with non-ARBs (0.37; 0.16-0.89). Incidence of study drug discontinuation due to adverse events was lower with candesartan than with non-ARBs (5.7 vs. 12.2%, P < 0.001).

Conclusion: Although candesartan showed no significant differences in MACE compared with the non-ARB treatment group, the drug significantly reduced the incidence of new-onset diabetes and was better tolerated. This study is registered as International Standard Randomised Controlled Trial No. UMIN000000790.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Angina Pectoris / epidemiology
  • Angina Pectoris / prevention & control
  • Angiotensin II Type 1 Receptor Blockers / therapeutic use*
  • Benzimidazoles / therapeutic use*
  • Biphenyl Compounds
  • Blood Pressure / drug effects
  • Coronary Artery Disease / drug therapy*
  • Coronary Artery Disease / surgery
  • Death, Sudden, Cardiac / epidemiology
  • Death, Sudden, Cardiac / prevention & control
  • Diabetes Mellitus / epidemiology
  • Diabetes Mellitus / prevention & control
  • Female
  • Heart Failure / epidemiology
  • Heart Failure / prevention & control
  • Humans
  • Hypertension / drug therapy*
  • Male
  • Middle Aged
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control
  • Statistics as Topic
  • Stroke / epidemiology
  • Stroke / prevention & control
  • Tetrazoles / therapeutic use*
  • Young Adult

Substances

  • Angiotensin II Type 1 Receptor Blockers
  • Benzimidazoles
  • Biphenyl Compounds
  • Tetrazoles
  • candesartan