Does initial combination therapy improve home systolic blood pressure reduction compared to sequential monotherapy in untreated patients with hypertension?
Initial combination therapy provides superior early blood pressure reduction compared to sequential monotherapy in untreated hypertensive patients.
Background Guidelines for hypertension vary in their preference for initial combination therapy or initial monotherapy, stratified by patient profile; therefore, we compared the efficacy and tolerability of these approaches. Methods and Results We performed a 1‐year, double‐blind, randomized controlled trial in 605 untreated patients aged 18 to 79 years with systolic blood pressure ( BP ) ≥150 mm Hg or diastolic BP ≥95 mm Hg. In phase 1 (weeks 0–16), patients were randomly assigned to initial monotherapy (losartan 50–100 mg or hydrochlorothiazide 12.5–25 mg crossing over at 8 weeks), or initial combination (losartan 50–100 mg plus hydrochlorothiazide 12.5–25 mg). In phase 2 (weeks 17–32), all patients received losartan 100 mg and hydrochlorothiazide 12.5 to 25 mg. In phase 3 (weeks 33–52), amlodipine with or without doxazosin could be added to achieve target BP . Hierarchical primary outcomes were the difference from baseline in home systolic BP , averaged over phases 1 and 2 and, if significant, at 32 weeks. Secondary outcomes included adverse events, and difference in home systolic BP responses between tertiles of plasma renin. Home systolic BP after initial monotherapy fell 4.9 mm Hg (range: 3.7–6.0 mm Hg) less over 32 weeks ( P 150/95 mm Hg. Clinical Trial Registration URL : http://www.ClinicalTrials.gov . Unique identifier: NCT 00994617.
MacDonald et al. (2017) studied this question.