Does blood pressure response vary? An assessment using a systematic review of calcium channel blockers for primary hypertension

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Mon Yee Wong M, M Wright J, Glasziou P

Background: The optimal strategy for monitoring and titration of patients commencing antihypertensive medication has not been systematically studied, despite existing guidelines for management of hypertension. While the magnitude of average blood pressure lowering addresses the efficacy, analyzing the variability of the blood pressure (BP) response provides additional information that can be applied to titration and monitoring.

Objective: To analyze the short-term variability of blood pressure responses to calcium channel blocker (CCB) treatment and placebo in patients with primary hypertension, using data from randomized controlled trials included in a systematic review of the blood pressure lowering efficacy of CCBs.

Methods: Search Strategy: Medline, EMBASE, CINAHL, the Cochrane Central Register of Controlled Trials, and bibliographic citations of relevant review articles were searched using an expanded version of the standard search strategy of the Cochrane Hypertension Group. Inclusion criteria: Randomized controlled trials in patients with primary hypertension (defined as baseline SBP œôù¥ 140 mm Hg and/or DBP œôù¥ 90 mm Hg) with a calcium channel blocker monotherapy arm and a parallel placebo arm; a duration of at least 3 weeks; blood pressure measurements reported at baseline and at one or more time points between 3 to 12 weeks after starting treatment. Analysis: The standard deviation (SD) of the change in systolic and diastolic blood pressure was extracted from all included trials reporting this data, and used to calculate a weighted mean value and associated variability for dihydropyridines, non-dihydropyridines, CCBs as a whole, and placebo. Those trials whose reported values were not within three standard deviations of the weighted mean were then excluded from the calculation. Student's t-tests were performed to compare the mean variabilities of BP change between CCB and placebo. A correlation analysis was performed to determine the relationship between the standard deviations of BP change for CCB treatment and for placebo.

Results: 106 studies (13,878 patients) were included in the systematic review, and of these, 37 (35%) of studies reported SD of change in SBP and/or DBP. There was no difference in weighted mean SD of the change in SBP between placebo and CCB treatment groups (14.1 mm Hg [SD 4.1] and 13.5 mm Hg [SD 2.1], respectively), nor in SD of DBP change (7.9 mm Hg [SD 2.3] and 7.8 mm Hg [SD 1.6], respectively). There was also no statistically significant difference in the variability of response between dihydropyridines and non-dihydropyridines. There is a strong linear correlation between SD of BP change for CCB and for placebo in the studies. The maximal placebo-corrected reduction in BP was -10/-7 mm Hg for dihydropyridines and -8/-6 mm Hg for non-dihydropyridines.

Conclusions: As there was no detectable significant difference in the variability of blood pressure response to CCB treatment and placebo, we conclude there is minimal true variation in response to a fixed dose of CCB treatment. The magnitude of this variability exceeds the maximal blood pressure reduction with CCB treatment, and consequent to this poor signal-to-noise ratio, it is difficult to make informed titration decisions based solely on office BP measurements. Given that current management of hypertension is target-driven, we propose a more rational strategy to monitor initial treatment response consisting of daily self-monitoring of blood pressure with a calibrated, automated device. The mean blood pressure and standard deviation calculated from home measurements over time can provide a more accurate reflection of the effect of treatment in an individual compared to office blood pressures.