Expedited blood pressure control with initial angiotensin II antagonist/diuretic therapy compared with stepped-care therapy in patients with ambulatory systolic hypertension

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The present study investigated whether initiating therapy with a combination of losartan (L) and hydrochlorothiazide (HCTZ) allows for faster blood pressure (BP) control and fewer medications than the usual stepped-care approach in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension. Patients with a mean daytime systolic ambulatory BP (ABP) of 135 mmHg or higher were randomly assigned to receive L 50 mg plus HCTZ 12.5 mg titrated to L 100 mg plus HCTZ 25 mg versus HCTZ 12.5 mg plus atenolol 50 mg. Amlodipine 5 mg was then added, if needed, to achieve a BP goal of less than 130 mmHg. Treatment titration was based on ABP. Significantly more patients randomly assigned to L/HCTZ (63.5%) than stepped-care (37.5%; P=0.008) achieved the primary end point (daytime systolic BP of less than 130 mmHg). Initial L/HCTZ induced significantly greater decreases in ABP during each 24 h period after six weeks of therapy. Although reductions in systolic and diastolic ABP were not statistically different at the end of the study, ABP reduction was significantly greater (P<0.001) with the L/HCTZ-based regimen. Twice as many patients in the L/HCTZ group achieved the goal ABP with no more than two drugs (30.0% versus 14.7%; P=0.03). Moreover, tolerability was significantly better (P=0.006) in the L/HCTZ group, with a 40.0% incidence of adverse events, versus 65.6% in the stepped-care group. Initiating antihypertensive therapy with the combination of L/HCTZ in patients with stage 2 or 3 hypertension and ambulatory systolic hypertension reaches a target BP faster in a higher proportion of patients, with fewer adverse events and less need for a third drug regimen than the conventional stepped-care approach.