Comparative effectiveness of chlorthalidone with hydrochlorothiazide using two ratios of potency in a real world managed care population

Abstract

Patients with hypertension whose blood pressure (BP) does not reduce during the nighttime period (non-dippers) are at increased risk of cardiovascular events. Antihypertensive therapies that improve the dip in BP from daytime to nighttime could improve outcomes beyond overall BPlowering. We investigated the efficacy of LCZ696 (Japanese Adopted Name: Sucabitril Valsartan Sodium Hydrate), a first-in-class angiotensin receptor neprilysin inhibitor (ARNI), in sub-populations of patients with hypertension classified as dippers ( 10% decrease in mean ambulatory [ma] systolic blood pressure [SBP] at nighttime vs. daytime) and non-dippers (<10% decrease in maSBP at nighttime vs. daytime) at baseline. This double-blind, placebo-controlled study was conducted in 389Asian patients with mild to moderate hypertension (mean sitting [ms] diastolic blood pressure [DBP] 95 and<110 mmHg and msSBP 140 and<180 mmHg) randomized to 8 weeks’ treatment with LCZ696 100, 200 or 400 mg, or placebo.Changes frombaseline in 24-h and nighttime (10 pm-6 am)maSBPand maDBP were assessed at Week 8 in dippers and non-dippers. Of 362 patients who completed the study, baseline characteristics (mean age 51.5 yrs [11% 65 yrs]; 72% male; BMI 25.9 kg/m) and baseline maBP (maSBP/maDBP) were similar between dippers (143.6/93.8 mmHg) and non-dippers (147.4/96.4 mmHg). 319 dippers or non-dippers had evaluable maBP measurements at baseline and post-baseline. All doses of LCZ696 provided significantly greater reductions in mean 24-h and nighttime maSBP and maDBP vs. placebo, with a trend (NS) for the greatest benefit observed with the two higher doses of LCZ696 in non-dippers (Table). Overall incidence of adverse events was similar between each treatment group (37.5-38.0%) and placebo (32.6%). These results suggest that the ARNI LCZ696 is an effective treatment for Asian patients with hypertension, reducing BP throughout the 24-h period and restoring nighttime BP reduction in non-dippers.