Is ARB/CCB Combination Superior to ARB/HCTZ Combination in Day-by-day Blood Pressure Variability Reduction? A Prospective Randomized Trial

Background: Day-by-day blood pressure variability (DDV) is an independent risk for cardiovascular events. An angiotensin II receptor blocker (ARB) combined with a Ca channel blocker (CCB) or hydrochlorothiazide (HCTZ) is an established option for combination therapy to achieve target blood pressure (BP). However, little is known about the effects of these combinations on DDV of home BP. Thus, we investigated whether ARB/CCB combination would be superior to ARB/HCTZ combination in DDV reduction. Methods: This prospective, randomized, open-labeled, multicenter trial enrolled 926 outpatients who had not achieved home BP target (<135/85 mmHg) despite antihypertensive medications. Patients were randomly assigned to receive a 8-mg candesartan/5-mg amlodipine tablet (ARB/CCB group) or a 8-mg candesartan/6.25-mg HCTZ tablet (ARB/HCTZ group) once every morning. Intra-individual DDV was assessed by standard deviation and coefficient of variance of systolic BP of home BP home BP of the consecutive 7 mornings. Results: After 6-month treatment, ARB/CCB and ARB/HCTZ reduced morning home BP and DDV to the similar levels. On subgroup analysis, ARB/CCB group showed greater reductions in morning home BP and DDV than ARB/HCTZ group in February, May, April, and October. Conclusions: Strict BP lowering is important for DDV reduction in home BP, irrespectively of antihypertensive regimen. ARB/CCB combination may have advantage to reduce DDV when the seasons change.