Effects of calcium-channel blocker benidipine-based combination therapy on cardiac events: Subanalysis of the COPE trial

Background: The Combination Therapy of Hypertension to Prevent Cardiovascular Events (COPE) trial was conducted to compare the effects of regimens combining the dihydropyridine calcium-channel blocker benidipine with each of 3 secondary agent types (an angiotensin-receptor blocker (ARB), a β-blocker and a thiazide) in Japanese hypertensive outpatients who did not achieve target blood pressure (<140/90 mmHg) with benidipine 4 mg/day alone. The analysis included 3,293 patients (ARB, 1,110; β-blocker, 1,089; thiazide, 1,094) with a median follow-up of 3.61 years. The main results of the COPE trial demonstrated that the incidences of hard cardiovascular composite endpoints and fatal or non-fatal strokes were significantly higher in the benidipine/β-blocker group than in the benidipine/thiazide group. Methods and Results: We further evaluated the treatment effects on different cardiac events among the 3 benidipine-based regimens. We observed a total of 50 cardiac events, 4.2 per 1000 person-years. The incidences of total cardiac events and each cardiac event were similarly low among the 3 treatment groups. Unadjusted and multi-adjusted hazard ratios for total cardiac events showed no significant difference among the 3 treatment groups. Conclusions: This subanalysis of the COPE trial demonstrated that blood pressure-lowering regimens combining benidipine with an ARB, β-blocker or thiazide diuretic were similarly effective for the prevention of cardiac events in Japanese hypertensive outpatients.