Efficacy of the combination of amlodipine and candesartan in hypertensive patients with coronary artery disease: a subanalysis of the HIJ-CREATE study

Abstract

Background: The effects of the combination of angiotensin II receptor blocker (ARB) plus dihydropyridine calcium channel blockers (DHP-CCBs), which is known as a potent antihypertensive drug regimen, on cardiovascular events remain unclear.

Objective: The purpose of this post hoc subgroup analysis was to compare the incidence of major adverse cardiovascular events (MACE) of patients treated with candesartan and amlodipine with that of those with candesartan and non-amlodipine CCBs in hypertensive patients with coronary artery disease (CAD).

Methods: HIJ-CREATE was a multicenter, prospective, randomized, controlled study that compared the effects of candesartan-based with those of non-ARB-based standard therapy on MACE in 2049 hypertensive patients with CAD. In the candesartan group, a total of 335 patients were treated with DHP-CCBs (amlodipine: 170 and non-amlodipine-CCBs: 165) at the baseline. In this sub-analysis, we compared, among the participants allocated to candesartan regimen, the long-term effects of amlodipine and non-amlodipine CCBs that were concomitantly given with ARB, although the choice of CCB was not randomized.

Results: The median follow-up was 3.9 years. Treatment using amlodipine with candesartan reduced the risk of MACE by 38% (hazard ratio, 0.62; 95% confidence interval, 0.41-0.94, p=0.025), as compared to patients treated with non-amlodipine-CCBs and candesartan. In a multivariate analysis, combination therapy of candesartan with amlodipine was an independent predictor of reduced risk of MACE.

Conclusions: The results suggest that the combination of amlodipine and candesartan is more beneficial in reducing MACE in hypertensive patients with CAD compared to non-amlodipine-DHP-CCBs in combination therapy with candesartan. Further investigation in larger-scale prospective randomized studies is required to reach any conclusion as to the superiority of combination therapy of candesartan with amlodipine.

Keywords: Amlodipine; Candesartan; Combination therapy; Coronary artery disease; Hypertension.