Key Points
- To compare the antihypertensive efficacy, safety, and dose-response relationship of losartan 50 mg versus losartan titrated to 100 mg against placebo in mild-to-moderate essential hypertension.
- Conducted a 12-week, double-blind, parallel-group, placebo-controlled trial of 366 patients with baseline mean sitting diastolic blood pressure of 101 ± 5 mmHg following a 4-week single-blind placebo lead-in.
- Randomized patients to placebo, losartan 50 mg, or losartan 50 mg with optional titration to 100 mg at week 6 if sitting diastolic blood pressure was ≥ 90 mmHg, utilizing mock titration in the other arms.
- Assessed peak (6 hours post-dose) and trough (24 hours post-dose) blood pressures, evaluated rebound hypertension during a 1-week post-trial off-drug period, and measured baseline plasma renin activity.
- At week 6, patients receiving losartan experienced significantly greater peak and trough reductions in sitting systolic and diastolic blood pressure compared with placebo (p ≤ 0.01).
- At week 12, both losartan regimens lowered trough sitting diastolic blood pressure more effectively than placebo, with only a very small incremental reduction gained from titrating losartan to 100 mg.
- No rebound hypertension was detected during the 1-week drug withdrawal period, and adverse-event incidence remained comparable between losartan and placebo.
Structured PICO
Does losartan 50 mg, with or without titration to 100 mg, reduce sitting blood pressure in patients with mild-to-moderate essential hypertension compared to placebo?
PPopulation366 patients with mild-to-moderate essential hypertension, group mean sitting diastolic blood pressure of 101 +/- 5 (s.d.) mmHg.
IInterventionLosartan 50 mg or losartan 50 mg with the option to titrate to 100 mg after the first 6 weeks if target sitting diastolic blood pressure (< 90 mmHg) was not reached.
CComparatorPlacebo (with mock titration at week 6 if sitting diastolic blood pressure >= 90 mmHg).
OOutcomeReduction in systolic and diastolic sitting blood pressures (peak and trough) at week 6 and week 12.surrogate
Losartan 50 mg, with optional titration to 100 mg, is effective and well-tolerated for lowering blood pressure in mild-to-moderate essential hypertension without causing rebound hypertension.