Comparison of the efficacy and tolerability of combination tablets containing candesartan cilexetil and hydrochlorothiazide or losartan and hydrochlorothiazide in patients with moderate to severe hypertension - Results of the CARLOS-Study

Objectives: To compare the fixed combinations of candesartan cilexetil and hydrochlorothiazide (HCTZ) and losartan and HCTZ with respect to magnitude and duration of antihypertensive effect and tolerability. Design and Setting: This was a randomised, double-blind, parallel-group study conducted at nine centres in Germany. Patients: 160 patients with moderate to severe hypertension, untreated or not controlled on previous treatment, completed the study. Interventions: Patients were randomised to 6 weeks of treatment with candesartan cilexetil and HCTZ 16/12.5mg once daily (n = 81) or losartan and HCTZ 50/12.5mg once daily (n = 79). Blood pressure measurements were performed approximately 24 and 48 hours after the last dose. Results: Both candesartan cilexetil/HCTZ and losartan/HCTZ lowered blood pressure significantly compared with baseline. Mean seated blood pressures were reduced by 32.2/21.1mm Hg (systolic/diastolic) after 6 weeks, 24 hours postdose, in the candesartan cilexetil/HCTZ group. Corresponding reductions in the losartan/HCTZ group were 23.8/14.9mm Hg. The mean differences in antihypertensive effect between treatments were 8.4/6.2mm Hg in favour of candesartan cilexetil (p < 0.001). Blood pressure reductions 48 hours postdose were 25.6/16.4mm Hg for candesartan cilexetil/HCTZ End 9.2/4.2mm Hg for losartan/HCTZ, with differences between treatments being highly significant in favour of candesartan cilexetil/HCTZ (16.5/12.2mm Hg; p < 0.001). The proportions of responders (seated diastolic blood pressure less than or equal to 90mm Hg and/or a reduction from baseline greater than or equal to 10mm Hg) and controlled patients (seated diastolic blood pressure less than or equal to 90mm Hg) on candesartan cilexetil/HCTZ were 98 and 58% at 24 hours, and 84 and 37% at 48 hours postdose. Corresponding figures for losartan/HCTZ were 79 and 28%, and 18 and 1.3%, respectively. All differences were significant (p < 0.001) in favour of candesartan cilexetil/HCTZ. Both treatments were well tolerated. Conclusions: Candesartan oilexetil/HCTZ 16/12.5mg once daily reduced blood pressure more effectively than losartan/HCTZ 50/12.5mg once daily both 24 and 48 hours postdose. The long-lasting effect of candesartan cilcxetil/HCTZ provides effective blood pressure control even Lifter a missed dose.