ABSTRACT

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

O. K. ANDERSSON,1 S. NELDAM2 FOR THE MC STUDY GROUP

From the1Sahlgrenska University Hospital, Go¨teborg, Sweden and2Rødovre Centrum, Rødovre, Denmark

Andersson OK, Neldam S, for the MC Study Group.Candesartan cilexetil, 16 mg, provides a greaterantihypertensive effect than losartan, 50 mg, in patients with mild to moderate hypertension.BloodPressure 2000; 9 (Suppl 1): 55 (abstr).

Candesartan is a new angiotensin II type 1 (AT1) receptor blocker, which binds tightly to and dissociatesslowly from the AT1-receptor. These binding characteristics underpin the long duration of action andantihypertensive efficacy of candesartan, and help to differentiate it from losartan, which was the firstAT1-receptor blocker to be approved for the treatment of hypertension. This study compared theantihypertensive effect and tolerability of candesartan cilexetil, 8 or 16 mg once daily, with that ofplacebo and of losartan, 50 mg once daily, in patients with mild to moderate primary hypertension. Thedose of 50 mg for losartan was chosen, as this is the dose usually recommended; higher doses do not seemto result in further reductions in blood pressure. Men and women, aged 20–80 years, with primaryhypertension and a sitting diastolic blood pressure (DBP) of 95–114 mmHg at the end of a 4-weekplacebo 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) for8 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 endof the study were assessed by analysis of variance. Patients were defined as having responded to treatmentif sitting DBP was 90 mmHg or below at week 8 or if sitting DBP had been reduced by more than10 mmHg from baseline to week 8. The proportion of responders in each treatment group was 15% forplacebo, 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 inpatients treated with candesartan cilexetil, 16 mg, than in patients treated with losartan, 50 mg (seeTable). 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 theincidence 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 thistype of patient population. In conclusion, candesartan cilexetil, 8 or 16 mg once daily, is an effective andwell-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 oncedaily.

Table.Reductions in sitting DBP at trough from baseline to week 8 were significantly greater in patients treated withcandesartan cilexetil, 16 mg, than in patients treated with losartan, 50 mg

Treatment comparisonAdjusted mean difference(95% confidence interval) Significance

Candesartan, 8 mg, vs placebo ÿ8.9 (ÿ11.8 toÿ6.0) p< 0.001Candesartan, 16 mg, vs placebo ÿ10.3 (ÿ13.2 toÿ7.4) p< 0.001Candesartan, 8 mg, vs losartan ÿ2.3 (ÿ5.3 toÿ0.6) p = 0.115Candesartan, 16 mg, vs losartan ÿ3.7 (ÿ6.7 toÿ0.8) p< 0.05

BLOOD PRESSURE 2000; 9 (Suppl 1): 55 Poster abstracts

2000 Taylor & Francis on licence from Blood Pressure. ISSN 0803-8023 BLOOD PRESSURE 2000

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