Researchers conducted the HIJ-CREATE ( The Heart Institute of Japan-Candesartan Randomized trial for Evaluation in Coronary Artery Disease ) trial to determine whether the angiotensin II receptor blocker ( ARB ) Candesartan ( Atacand, ratacand ) would reduce cardiovascular events more than angiotensin-converting enzyme inhibitor therapy ( ACE inhibitors ) in patients with documented hypertension and coronary artery disease.

Using a multi-center approach, researchers conducted a randomized, open-label, blinded-endpoint trial that included follow-up visits scheduled at 6, 12, 24, 36, 48 and 60-month intervals.
They randomly gave 2,049 patients either Candesartan-based therapy without any ACE inhibitors or non-ARB-based standard treatment at 14 sites in Japan between June 2001 and April 2004.
About 35 percent of the patients had suffered a prior acute coronary syndrome and 38 percent had suffered a prior myocardial infarction.

The primary endpoint of the study was to determine the amount of time that would pass until the first major adverse cardiovascular event ( MACE: death from cardiovascular cause, non-fatal myocardial infarction, unstable angina pectoris, heart failure, stroke and other cardiovascular events, which required hospitalisation ).
The major secondary endpoints included the incidence of coronary revascularization and new-onset diabetes.

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; p=0.19 ).
However, Candesartan significantly reduced the incidence of the primary end points at 3-6 months after randomization ( HR=0.55; p=0.021 ).

The new onset rate with Candesartan and non-ARB standard therapy were 1.1% and 2.9% respectively. ( p=0.027 )

In patients with impaired renal function, Candesartan showed 21% reduction in incidence of MACE as compared to the non-ARB standard therapy. ( p=0.039 )

“ Candesartan therapy may reduce the incidence of MACE in patients with impaired renal function in addition to reduction of new onset of diabetes mellitus,” said the chief investigator of The HIJ-CREATE, Hiroshi Kasanuki, at Tokyo Women’s Medical University. “ Although there is no statistically significant difference in primary endpoint between Candesartan therapy and non-ARB standard therapy, drug-related adverse events were lesser in Candesartan therapy, and the results are meaningful in view of the increasing attention to the importance of organ protection by suppression of renin-angiotensin system for coronary artery disease patients with hypertension.”

Source: American Heart Association’s Scientific Sessions, 2007

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