Candesartan Cilexetil, 16 mg, Provides a Greater Antihypertensive Effect than Losartan, 50 mg, in Patients with Mild to Moderate Hypertension

Abstract

Candesartan is a new angiotensin II type 1 (AT 1 ) receptor blocker, which binds tightly to and dissociates slowly from the AT 1 -receptor. These binding characteristics underpin the long duration of action and antihypertensive efficacy of candesartan, and help to differentiate it from losartan, which was the first AT 1 -receptor blocker to be approved for the treatment of hypertension. This study compared the antihypertensive effect and tolerability of candesartan cilexetil, 8 or 16 mg once daily, with that of placebo and of losartan, 50 mg once daily, in patients with mild to moderate primary hypertension. The dose of 50 mg for losartan was chosen, as this is the dose usually recommended; higher doses do not seem to result in further reductions in blood pressure. Men and women, aged 20-80 years, with primary hypertension and a sitting diastolic blood pressure (DBP) of 95-114 mmHg at the end of a 4-week placebo run-in period, were randomized to once-daily, double-blind treatment with candesartan cilexetil, 8 mg ( n = 82), candesartan cilexetil, 16 mg ( n = 86), losartan, 50 mg ( n = 84), or placebo ( n = 85) for 8 weeks. Blood pressure was measured 6 and 24 h after dosing, i.e. at the times of peak and trough effects, respectively. Differences among treatments in changes in blood pressure from randomization to the end of the study were assessed by analysis of variance. Patients were defined as having responded to treatment if sitting DBP was 90 mmHg or below at week 8 or if sitting DBP had been reduced by more than 10 mmHg from baseline to week 8. The proportion of responders in each treatment group was 15% for placebo, 46% for losartan, 50 mg, 50% for candesartan cilexetil, 8 mg, and 57% for candesartan cilexetil, 16 mg. The reduction in sitting DBP at trough (the primary effect variable) was significantly greater in patients treated with candesartan cilexetil, 16 mg, than in patients treated with losartan, 50 mg (see Table). In addition, both doses of candesartan cilexetil had a trough-to-peak ratio of approximately 1.0, compared with 0.7 for losartan. Both candesartan cilexetil and losartan were well tolerated, with the incidence of adverse events similar to placebo in both treatment groups. Overall, the most common new-onset adverse events reported were headache and respiratory infection, both of which are common in this type of patient population. In conclusion, candesartan cilexetil, 8 or 16 mg once daily, is an effective and well-tolerated antihypertensive treatment, with a trough-to-peak ratio close to 1.0. Candesartan cilexetil, 16 mg once daily, produces a significantly greater reduction in blood pressure than losartan, 50 mg once daily.