Effects of calcium channel blocker-based combinations on intra-individual blood pressure variability: post hoc analysis of the COPE trial

Abstract

Visit-to-visit blood pressure (BP) variability is an important predictor of stroke. However, which antihypertensive drug combination is better at reducing visit-to-visit BP variability and therefore at reducing stroke incidence remains uncertain. We have previously reported that the dihydropyridine calcium channel blocker benidipine combined with a β-blocker appeared to be less beneficial in reducing the risk of stroke than a combination of benidipine and thiazide. Here, we further compare the visit-to-visit BP variability among three benidipine-based regimens, namely angiotensin receptor blocker (ARB), β-blocker and thiazide combinations. The present post hoc analysis included 2983 patients without cardiovascular events or death during the first 18 months after randomization. We compared the BP variability (defined as the s.d. and the coefficient of variation (CV)), maximum systolic BP (SBP) and diastolic BP (DBP) of the clinic mean on-treatment BPs obtained at 6-month intervals, starting 6 months after the treatment initiation, among the 3 treatments (ARB, n=1026; β-blocker, n=966; thiazide, n=991). During the first 6-36 months after randomization, both the s.d. and CV-BPs were lower in the benidipine-thiazide group than in the benidipine-β-blocker group (s.d.-SBP, P=0.019; s.d.-DBP, P=0.030; CV-SBP, P=0.012; CV-DBP, P=0.022). The s.d. and CV in the ARB group did not reach statistical significance compared with the other two groups. The maximum BPs did not differ among the three treatments. These findings suggest that the benidipine-thiazide combination may reduce visit-to-visit BP variability more than the benidipine-β-blocker combination.

Trial registration: ClinicalTrials.gov NCT00135551.

Figure 1

Flow diagram of the study participants. The blood pressure was measured at six time points (6, 12, 18, 24, 30, and 36 months after randomization) and was used to determine the mean, maximum and minimum, and intra-individual visit-to-visit variability of systolic and diastolic BPs. After excluding patients who had experienced any cardiovascular events within 18 months after randomization and patients with missing BP values from 3 or more of the 6 time points, 2983 patients were eligible for enrollment in the present study. ARB, angiotensin receptor blocker; BP, blood pressure; COPE, Combination Therapy of Hypertension to Prevent Cardiovascular Events.