Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COMPAS-BPV)

Abstract

BACKGROUND Antihypertensive therapy using renin–angiotensin system blockers and calcium channel blockers to target blood pressure variability (BPV) has not yet been established. We aimed to compare the ability of losartan and amlodipine to lower BPV and systolic blood pressure (SBP) in essential hypertensive patients. METHODS Patients were randomly assigned either losartan 50 mg or amlodipine 5 mg. Medications were uptitrated and hydrochlorothiazide was added according to protocol for 6 months. The primary endpoint was the office visit-to-visit SD of SBP. The secondary endpoints included average real variability (ARV), office SBP, and home SBP. RESULTS The losartan group (n = 71) and amlodipine group (n = 73) finished the scheduled visits between April 2013 and May 2017. The office visit-to-visit SD of SBP was comparable between the losartan and amlodipine groups (11.0 ± 4.2 vs. 10.5 ± 3.8, P = 0.468). The office visit-to-visit ARV of SBP was significantly elevated in the losartan group (10.6 ± 4.3 vs. 9.1 ± 3.4, P = 0.02). The absolute SBP decrement from baseline to 6 months was similar between groups, although the office mean SBP at 6 months was higher in the losartan group (132.3 ± 12.9 vs. 127.5 ± 9.0 mm Hg, P = 0.011). In home blood pressure analysis, evening day-to-day BPV indexes (SD and ARV) were significantly higher in the losartan group at 6 months. CONCLUSIONS The lowering effect of the office visit-to-visit SD of SBP was similar between losartan and amlodipine. However, the losartan group showed a higher office visit-to-visit ARV of SBP and evening day-to-day home BPV indexes. Therefore, amlodipine may be better to lower BPV in essential hypertensive patients.

Blood pressure and variability responses to the down-titration of antihypertensive drugs

“…Conversely, the negative effect of beta-blockers on blood pressure variability is hypothesized to be associated with a decrease in heart rate or influenced by beta-1 selectivity [26,27]. Relatively longer half-life of CCB might also have contributed to these effects [28]. Moreover, the relatively slight alteration in BP upon discontinuing beta-blockers could also be considered as one of the contributing factors, as shown in Table S2, http:// links.lww.com/HJH/C390.…”

Effect of dihydropyridine calcium channel blockers on blood pressure variability in the SPRINT trial: a treatment effects approach

“…In addition, as we attempted to minimize confounding from imbalances between our study groups through AIPW and LASSO, we may have reduced bias in our estimation of the impact of adding a dihydropyridine CCB to an intensive blood pressure-lowering regimen. The Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COM-PAS-BPV) trial was the first prospective randomized trial that attempted to reduce vvBPV [17]. In 144 participants with essential hypertension, 73 received an increasing dose of amlodipine/hydrochlorothiazide and 71 received losartan/hydrochlorothiazide.…”

“…The Comparison of Blood Pressure Variability Between Losartan and Amlodipine in Essential Hypertension (COMPAS-BPV) trial was the first prospective randomized trial that attempted to reduce vvBPV [17]. In 144 participants with essential hypertension, 73 received an increasing dose of amlodipine/hydrochlorothiazide and 71 received losartan/hydrochlorothiazide.…”

“…Prior research has also demonstrated that patients with increased vvBPV are at elevated risk of all-cause mortality in disease states ranging from coronary artery disease to diabetes [11][12][13][14][15][16]. However, apart from a small trial [17], there has not been prospective clinical research that attempted to lower BPV, either as a visit-to-visit or short-term outcome. In part, this is not only because of uncertainty if increased BPV is causal of worse outcome but also as there is no proven medication strategy to reduce BPV [18].…”

“…The antihypertensive exposure is determined by randomization or self-reported medication use at a single point in time, the outcome of BPV is often captured at infrequent intervals with different measurement methodology, and the research is largely from studies that predate the intensive blood pressure lowering that has followed the SPRINT trial [18,23,25]. However, prior research, including a small clinical trial, has consistently shown an association between lower vvBPV and calcium channel blocker (CCB) antihypertensive medications, specifically dihydropyridine CCBs, such as amlodipine [17,20,24,[26][27][28]. To validate this finding, we performed a post hoc analysis of the SPRINT trial in which we leveraged the granularity of data on medications and the standardized blood pressure measurement and management to fit a sophisticated treatment effects model that estimates the causal impact of dihydropyridine CCBs on vvBPV.…”