In patients with hypertension with blood pressure (BP) >150/95 mm Hg, initial combination therapy of losartan and hydrochlorothiazide can be a recommended treatment approach, according to findings from a randomized trial published in the Journal of the American Heart Association.

In this 1-year double-blind trial, investigators randomly assigned patients with untreated hypertension (systolic BP ≥150 mm Hg or diastolic BP ≥95 mm Hg) to either initial monotherapy (n=301) or initial combination therapy (n=304).

Initial monotherapy consisted of 12.5 mg to 25 mg hydrochlorothiazide or 50 mg to 100 mg losartan with crossover at 8 weeks, and initial combination therapy consisted of 50 mg to 100 mg losartan plus 12.5 mg to 25 mg hydrochlorothiazide during phase 1 (weeks 0 to 16). All patients in the study received 12.5 mg to 25 mg hydrochlorothiazide and 100 mg losartan in phase 2 (weeks 17 to 32).

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Following initial monotherapy, home systolic BP decreased by 4.9 mm Hg (range: –6.0 to 3.7 mm Hg) less than after initial combination therapy during a 32-week period (P <.001). The differences, however, became similar at 32 weeks (difference: 1.2 mm Hg [range:–0.4 to 2.8 mm Hg]; P =.13).

Systolic BP in patients in the top renin tertile decreased by 4.3 mm Hg with hydrochlorothiazide and increased by 3.7 mm Hg with losartan vs patients in the lowest tertile (P <.001). Response to combination therapy was found to be similar in the renin tertiles, with a 5-mm Hg greater response than with monotherapy.

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Since the findings are limited to just one year, the study is unable to provide insight into the full effect of combination therapy vs monotherapy with these agents on morbidity and mortality.

The investigators believe that the use of initial combination therapy with losartan and hydrochlorothiazide in patients with hypertension “obviates the routine measurement of plasma renin, but extreme values can help the selection of monotherapy when desired.”


MacDonald TM, Williams B, Webb DJ, et al. Combination therapy is superior to sequential monotherapy for the initial treatment of hypertension: a double-blind randomized controlled trial [published online November 18, 2017]. J Am Heart Assoc. doi:10.1161/JAHA.117.006986