Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease - HIJ-CREATE
The goal of the trial was to evaluate treatment with the angiotensin receptor blocker candesartan compared with standard therapy without an angiotensin receptor blocker in patients with coronary artery disease and hypertension.
Patients Enrolled: 2049
Mean Follow Up: Mean follow-up 4.2 years
Angiographically documented coronary artery disease and hypertension, defined as SBP ≥140 mm Hg, DBP ≥90 mm Hg, or current use of antihypertensive medication.
Major cardiovascular event, defined as CV death, MI, unstable angina, heart failure, stroke or CV hospitalization
Revascularization, new onset diabetes
Patients were randomized in an open-label manner to treatment with candesartan without an ACE-inhibitor (n = 1024) or standard therapy without an ARB (n = 1025). The target blood pressure was less than 130 / 85 mm Hg.
The majority of patients in the trial had stable coronary artery disease (65%) while 35% had an acute coronary syndrome. Approximately one-third had a prior MI. There was no difference in the primary endpoint of major cardiovascular events between groups, which occurred in 25.8% of the candesartan group and 28.1% of the standard therapy group (relative risk [RR] 0.89, 95% CI 0.76-1.06, p = 0.19). Among the components of the composite, there were no significant differences, but the point estimate for CV death or MI fell in favor of standard therapy (p = 0.53) while the point estimates for the remaining endpoints fell in favor of candesartan. There was also no difference in the secondary endpoint of revascularization (25.0% for candesartan vs. 26.4% for standard therapy, p = 0.41). New onset diabetes, however, was reduced in the candesartan group (1.1% vs. 2.9%, p = 0.027). Drug-related adverse events were lower in the candesartan group (p = 0.027), as was study drug discontinuation (p < 0.001).
Among patients with coronary artery disease and hypertension, treatment with the angiotensin receptor blocker candesartan was not associated with a difference in major CV events at a median follow-up of 4.2 years compared with standard therapy without an ARB.
Despite a lack of difference in the primary endpoint, there did not appear to be harm in the ARB group, and there was a significant reduction in the secondary endpoint of new onset diabetes, suggesting candesartan may be an alternate therapy to ACE-inhibitors in this population. Results of the present study are similar to those of the VALIANT trial, which enrolled patients with acute MI and found that ARBs were non-inferior to ACE inhibitors in reducing cardiovascular events.
Presented by Dr. Hiroshi Kasanuki at the American Heart Association Annual Scientific Session, Orlando, FL, November 2007.
Sugiura R, Ogawa H, Oka T, Koyanagi R, Hagiwara N; HIJ-CREATE Investigators.Candesartan-based therapy and risk of cancer in patients with systemic hypertension (Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease [HIJ-CREATE] substudy). Am J Cardiol. 2012 Feb 15;109(4):576-80.
Keywords: Angiotensin Receptor Antagonists, Risk, Coronary Artery Disease, Acute Coronary Syndrome, Follow-Up Studies, Benzimidazoles, Tetrazoles, Hypertension, Diabetes Mellitus
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