AHA - 2007: Heart Institute of Japan Candesartan Randomized Trial for evaluation of Coronary Artery Disease: HIJ-CREATE

Heart Institute of Japan Candesartan Randomized Trial for evaluation of Coronary Artery Disease: HIJ-CREATE


Vijay Kunadian MBBS MD MRCP


ORLANDO, Nov. 7: The HIJ-CREATE trial was presented by Dr. Hiroshi Kasanuki, M.D. from Tokyo Women’s Medical University at the American Heart Association, Scientific Sessions 2007.


This study demonstrated that the use of candesartan was not associated with a significant difference in major cardiovascular events at a median follow-up of 4.2 years compared to standard medical therapy without the use of candesartan in patients with coronary artery disease and hypertension.


Briefly, this study evaluated the use of candesartan (angiotensin receptor blocker-ARB) compared to standard medical therapy without the use of an ARB in patients with a history of coronary artery disease and hypertension to determine if there was a reduction in cardiovascular events using candesartan.


In this study patients were randomized to treatment with candesartan or standard medical therapy without the use of the ARB in an open-label manner. The target blood pressure was 130/85 mmHg. Patients were followed up at 6, 12, 24, 36, 48 and 60-month intervals. In total 1024 patients were in the candesartan group and 1025 patients were in the standard medical therapy group. Patients were recruited from 14 sites in Japan between June 2001 and April 2004. The primary endpoint of the study was to determine the time to occurrence of first major adverse cardiovascular event. The major secondary endpoints included the incidence of coronary revascularization and new-onset diabetes.


About 35% of the patients had suffered a prior acute coronary syndrome and 38% had suffered a prior myocardial infarction. The ARB-based approach was associated with significantly fewer drug-related adverse events (p=0.027), and fewer patients discontinued the ARB than the ACE inhibitor (p<0.001). Patients in the ARB group had significantly less cough (p<0.001). There were no differences in development of dizziness, hyperkalemia, or liver dysfunction. There were 552 primary events during a mean follow-up of 4.2 years: 264 (25.8%) in the candesartan group and 288 (28.1%) in the non-ARB group (relative risk 0.89 [95% CI 0.76-1.06], p=0.19). There was no difference in the occurrence of revascularization between the candesartan and the standard therapy groups [25% vs. 26.6%, RR 0.92 (0.77-1.12), p=0.41]. There was a difference in the occurrence of new-onset diabetes in the ARB and the standard therapy groups [1.1% vs. 2.9%, RR 0.37 (0.15-0.94), p=0.04]. In patients with creatinine clearance <60ml/min, the HR was 0.79 (0.63-0.99), p=0.039.


Therefore, the HIJ CREATE study demonstrated that candesartan did not significantly improve the occurrence of major adverse cardiac events compared to standard medical therapy at a median follow-up of 4.2 years. However, candesartan was associated with fewer adverse effects. Treatment with candesartan may be beneficial in patients with glucose metabolism abnormalities and those with mild to moderate renal dysfunction. These findings are comparable to the VALIANT study which was conducted in patients with acute myocardial infarction.


References: Originally presented at AHA Scientific Sessions 2007.