Antihypertensive efficacy and safety of losartan alone and in combination with hydrochlorothiazide in adult African Americans with mild to moderate hypertension

Background. African Americans with hypertension, particularly those with mo re severe blood pressure elevations., are generally less responsive to mono therapy from any antihypertensive class. These patients usually require tre atment with drugs from greater than or equal to2 antihypertensive classes t o achieve adequate blood pressure control. Objective: The purpose of this study was to assess the antihypertensive eff icacy and safety of losartan alone and in combination with hydrochlorothiaz ide (HCTZ) in African American adults with mild to moderate hypertension. Methods: In this 12-week, multicenter, double-blind, randomized, parallel-g roup, placebo-controlled study, African American patients were randomized i n a 3:1:1 ratio to I of 3 treatment groups: placebo, losartan monotherapy ( 50 to 150 mg), or losartan plus HCTZ (50/0 to 50/12.5 to 100/25 mg). Doses were titrated at weeks 4 and 8 if sitting diastolic blood pressure (SiDBP) was greater than or equal to 90 mm Hg. Safety was assessed by determining t he incidence of clinical and laboratory adverse events and evaluating mean changes in pulse, body weight, electrocardiographic parameters, and laborat ory test results. Results: A total of 440 patients were randomized- 188 to placebo, 193 to lo sartan monotherapy, and 59 to losartan/HCTZ; 391 completed the study, At we ek 12, the response rate with losartan monotherapy was 45.8%. with a signif icant (P less than or equal to 0.01) lowering in mean SiDBP by 6.6 min Hg c ompared with placebo;, the response rate with placebo was 27.2%, with a mea n SiDBP reduction of 3.9 mm Hg. Sitting systolic blood pressure (SiSBP) was significantly lowered with losartan monotherapy, by 6.4 mm Hg, compared wi th placebo (reduction of 2.3 nim Hg). The response rate with losartan/ HCTZ was 62.7%. with reductions in SiSBP and SiDBP or 16.8 min Hg and 10.8 min Hg. respectively (P less than or equal to 0.01 vs placebo and losartan mono therapy). The incidence of clinical adverse events was comparable in the 3 treatment groups. Conclusions: The results of this study suggest that in African American pat ients, losartan monotherapy was significantly more effective than placebo i n lowering SiSBP and SiDBP. Moreover, the losartan/ HCTZ combination regime n resulted in significant and clinically meaningful additional reductions i n SiSBP and SiDBP compared with losartan monotherapy or placebo. Losartan m onotherapy and the losartan/HCTZ regimens were generally as well tolerated as placebo.