Losartan with hydrochlorothiazide in the treatment of hypertension

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Aim:To review the efficacy and safety of losartan and hydrochlorothiazide compared to losartan alone, hydrochlorothiazide alone or placebo in the treatment of mild to moderate hypertension in a clinical trialPatients and methods:A randomly allocated, placebo-controlled, double-blind parallel study was performed in 40 clinical centers throughout the United States. A total of 703 males and females aged 18–75 years with a sitting diastolic blood pressure of 95–115 mmHg entered the trial and 604 completed the 12-week protocol. The participants were randomly assigned to concomitant therapy once a day with: (1) 50 mg losartan and 6.25 mg hydrochlorothiazide, (2) 50 mg losartan and 12.5mg hydrochlorothiazide, (3) 50 mg losartan alone, (4) 12.5 mg hydrochlorothiazide alone or (5) placebo. All participants were followed for 12 weeksResults:At baseline, mean trough sitting diastolic blood pressure was 100.9-101.7 mmHg, with no significant difference between treatment groups. Sitting diastolic blood pressure fell 4.0 mmHg with placebo, 7.2 mmHg with 12.5mg hydrochlorothiazide, 7.2 mmHg with 50 mg losartan, 9.3 mmHg with 50 mg losartan + 6.25 mg hydrochlorothiazide, and 13.2 mmHg with 50 mg losartan + 12.5 mg hydrochlorothiazide. The fall in mean trough sitting systolic blood pressure was 2.4, 9.3, 10.7, 12.0 and 17.9 mmHg for the respective groups. After subtracting the placebo effect, the reductions in blood pressure induced by losartan and hydrochlorothiazide were additive for both sitting diastolic and systolic blood pressures and approximately equaled the reduction seen with the combination of losartan and hydrochlorothiazide. There were no significant differences in adverse events between treatment groupsConclusions:The concomitant administration of 50 mg losartan +12.5 mg hydrochlorothiazide produced additive falls in sitting diastolic and systolic blood pressures which were greater than that achieved with either drug alone. On the basis of the adverse effects reported, the combination was well tolerated

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