Losartan potassium as initial therapy in patients with severe hypertension.

This 12-week, open-label study was conducted to gain experience with losartan potassium, an angiotensin II receptor antagonist, in patients with severe hypertension. Patients were either untreated or withdrawn from current therapy for at least 48 h before initiation of losartan 50 mg once daily. Patients were titrated to 100 mg as needed to achieve a goal of sitting diastolic blood pressure (SiDBP) 90 or 95 mm Hg. Hydrochlorothiazide (12.5 mg once daily titrated to 25 mg) was added and followed by either a dihydropyridine calcium channel blocker (CCB) and/or atenolol, if BP was not controlled. A total of 179 patients with a pretreatment mean baseline BP of 172 +/- 17/112 +/- 18 mm Hg enrolled in the trial and BP was recorded 24 h after dosing at baseline and weeks 2, 4, 8 and the final week (10-12 weeks). The mean reductions in SiDBP from baseline were 7.3, 9.3, 15.9 and 18.9 mm Hg, respectively, and these changes from baseline were statistically significant, P < 0.001. At the end of the trial, 22% of patients remained on losartan monotherapy, 30% required the addition of hydrochlorothiazide (HCTZ) and 31% required both HCTZ and a CCB; 11% required HCTZ and atenolol while 4% required HCTZ, a CCB and atenolol; 2% of patients were on regimens not specified by the protocol. SiDBP < 90 mm Hg was achieved in 68 patients by the final visit; 24% of these patients were treated with losartan monotherapy (50 or 100 mg), 41% achieved control with the addition of HCTZ (12.5 or 25 mg) and 24% required triple therapy which included losartan, HCTZ and a CCB. As assessed by the investigator, 25% of the patients in the study had drug-related clinical adverse experiences. Headache was the most frequently reported clinical adverse event (26% of patients). No clinically significant changes in laboratory parameters were observed. It is concluded that losartan potassium can be used as initial therapy for patients with severe hypertension and can be administered concurrently with hydrochlorothiazide, calcium channel blockers and atenolol.