Combined Effect of Angiotensin II Receptor Blocker and Either a Calcium Channel Blocker or Diuretic on Day-by-Day Variability of Home Blood Pressure: The Japan Combined Treatment With Olmesartan and a Calcium-Channel Blocker Versus Olmesartan and Diuretics Randomized Efficacy Study

Abstract

Day-by-day home blood pressure (BP) variability (BPV) was reported to be associated with increased cardiovascular risk. We aimed to test the hypothesis that the angiotensin II receptor blocker/calcium-channel blocker combination decreases day-by-day BPV more than the angiotensin II receptor blocker/diuretic combination does and investigated the mechanism underlying the former reduction. We enrolled 207 hypertensive subjects treated with olmesartan monotherapy for 12 weeks. The subjects were randomly assigned to treatment with hydrochlorothiazide (n=104) or azelnidipine (n=103) for 24 weeks. Home BP was taken in triplicate with a memory-equipped device in the morning and evening, respectively, for 5 consecutive days before each visit. Visits occurred at 4-week intervals. Home BPV was defined as within-individual SD of the 5-day home BP. Arterial stiffness was assessed by aortic pulse wave velocity at baseline and 24 weeks later. The reductions in home systolic BP were similar between the 2 groups, whereas the SD of home systolic BP decreased more in the azelnidipine group than in the hydrochlorothiazide group during the follow-up period (follow-up mean: 6.3 versus 7.1 mm Hg; P =0.007). In the azelnidipine group, the change in aortic pulse wave velocity was independently associated with the change in SD of home systolic BP (regression coefficient±SE=0.79±0.37; P =0.036). This study demonstrated that the angiotensin II receptor blocker/calcium-channel blocker combination improved home BPV in addition to home BP reduction and that the reduction in home BPV was partly attributable to the arterial stiffness reduction by this combination.