Combined Effect of Angiotensin II Receptor Blocker and Either a Calcium Channel Blocker or Diuretic on Day-by-Day Variability of Home Blood Pressure

Abstract

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 (nϭ104) or azelnidipine (nϭ103) 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; Pϭ0.007). In the azelnidipine group, the change in aortic pulse wave velocity was independently associated with the change in SD of home systolic BP (regression coefficientϮSEϭ0. 79Ϯ0.37; Pϭ0.036). This study demonstrated that the angiotensin II receptor blocker/calciumchannel 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. (Hypertension. 2012;59:1132-1138.) • Online Data Supplement Key Words: home blood pressure Ⅲ day-by-day home blood pressure variability Ⅲ calcium channel blocker Ⅲ thiazide diuretic Ⅲ angiotensin II receptor blocker Ⅲ pulse wave velocity T here is a growing body of evidence that visit-to-visit blood pressure (BP) variability (BPV) in a clinical setting was significantly associated with target organ damage [1][2][3][4][5][6] and that it could predict cardiovascular events independent of mean office BP level.7-10 One drawback of the application of visit-to-visit office BPV for the routine clinical management of hypertension is that obtaining it requires several office visits over a period of time. One possible way to solve this is to evaluate day-by-day home BPV, because this selfmeasurement makes it possible to obtain multiple BP values in a relatively short period under well-controlled conditions. 11It was reported recently that the increased day-by-day home BPV, calculated as the SD of home BP, was associated with the severity of target organ damage in patients with hypertension 12 or diabetes mellitus 13 and with cardiovascular mortality in a community-dwelling population.14 After treat- Thus, these results 15,16 raised speculation that the difference in cardiovascular events that favored the CCB regimen was not explained by BP differences but, rather, by the favorable effect...

Dose Timing of an Angiotensin II Receptor Blocker/Calcium Channel Blocker Combination in Hypertensive Patients With Paroxysmal Atrial Fibrillation

“…Matsui and colleagues 22 also reported that the combination of olmesartan and azelnidipine reduced the SD of home SBP significantly more than the combination of olmesartan and a thiazide diuretic (À1.7 mm Hg vs À0.6 mm Hg; P=.01), and that the SD of home SBP was an independent determinant of aortic pulse wave velocity, indicative of arteriosclerosis. In the present study, the change in SD of home SBP was À2.2 mm Hg in both the morning and bedtime administration groups, which is consistent with the results reported by Matsui and colleagues.…”

“…22 The home BP variability included the standard deviation (SD), the coefficient variation (CV), the maximum BP, and the morning minus evening BP. The SD and CV values were calculated based on the average daily BP (four readings daily) of five consecutive days, 22 the maximum BP defined as the highest average among the average duplicate morning BP and average duplicate evening BP values, 23 and the morning minus evening BP as the difference between the daily morning BP and the evening BP. Clinic BP was determined at the participating study sites to measure BP three times at each visit.…”

Recent Clinical Trials of Hypertension Management

“…26 Day-to-day variability of home BP measurements was reduced significantly by a combination of angiotensin II receptor blocker and calcium channel blocker, and by more than an angiotensin II receptor blocker/diuretic combination in a Japanese study, perhaps because of effects on arterial stiffness. 27 ASCOT showed better outcomes with a regimen of amlodipine with or without perindopril than with atenolol with or without bendroflumethiazide. This finding plays a key part in the transatlantic debate on guidelines for the management of hypertension, favoring the ABCD approach, 28 recently updated to ACD (A-angiotensin inhibition, B-beta antagonist, C-calcium channel blocker, and D-diuretic) to initial therapy adopted by previous UK National Institute of Clinical Excellence (NICE) guidelines over the US Joint National Committee (JNC7) recommendation to commence therapy with a thiazide diuretic.…”

Calcium Antagonist Added to Angiotensin Receptor Blocker: A Recipe for Reducing Blood Pressure Variability?

“…A recent meta-analysis on the effects of different drug classes on visit-to-visit office BP variability can hardly be considered conclusive, because it was based on the retrospective assessment of interindividual rather than of intraindividual BP variability, a statistical approach of questionable validity. 6 The article by Matsui et al 7 published in the present issue of Hypertension provides an important contribution with regard to the effects of antihypertensive drugs on BPV. It reports the results of a post hoc analysis of Japan Combined Treatment With Olmesartan and a Calcium-Channel Blocker Versus Olmesartan and Diuretics Randomized Efficacy Study, where patients initially treated with an angiotensin antagonist (olmesartan) were randomly assigned to receive additionally either a CCB (azelnidipine) or a diuretic (hydrochlorothiazide).…”