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

Abstract

Objectives: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Figures

Figure 1)

Design of study comparing the effects of fixed-dose combination therapy using losartan and hydrochlorothiazide (HCTZ) as initial therapy with the stepped-care approach using HCTZ as initial therapy. *Ambulatory blood pressure monitoring; †Titration or addition according to mean daytime ambulatory systolic blood pressure of 130 mmHg or higher

Figure 2)

Histogram of the cumulative proportion of patients attaining the mean ambulatory daytime systolic blood pressure target of less than 130 mmHg at six, 12 and 18 weeks