Candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in unselected patients with high or very high cardiovascular risk: efficacy, safety, and metabolic impact.

BACKGROUND AND OBJECTIVES

Safety and efficacy of the fixed-dose combination candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg has been demonstrated in a number of randomized clinical trials. Because stringent inclusion and exclusion criteria prohibit many high-risk patients from being investigated in clinical trials we aimed to assess the effectiveness, tolerability, and safety in a large unselected cohort of high-risk patients in primary care. The primary objective was the efficacy of candesartan cilexetil 32 mg/hydrochlorothiazide 25 mg in lowering the office-based blood pressure (BP). Secondary objectives were changes of metabolic parameters and safety.

METHODS

A multicenter, non-interventional study of patients with a BP ≥ 140 mmHg systolic and/or 90 mmHg diastolic and additional cardiovascular risk factors. Patients received the fixed-dose combination of candesartan cilexetil 32 mg and hydrochlorothiazide 25 mg for 24 weeks.

RESULTS

A total of 3,390 patients with a mean age of 61.7 ± 10.6 years, 57.8 % being male, and a mean body mass index of 29.7 kg/m(2) were documented. Of these, 70.9 % had at least one additional cardiovascular risk factor such as coronary artery disease (45.5 %) or diabetes mellitus (44.5 %). Baseline BP was 159.6 ± 15.3 over 93.5 ± 9.5 mmHg. BP at 24 weeks was reduced by 32.3 ± 15.8 systolic and 16.1 ± 10.2 mmHg diastolic compared with baseline (p < 0.001 each). Systolic BP (SBP) and diastolic BP (DBP) was normalized (<140/<90 mmHg) in 57.4 % of non-diabetic patients. An SBP <140 mmHg or SBP reduction of ≥ 20 mmHg was achieved by 77.9 % non-diabetic patients. Fasting plasma glucose (-5.9 mg/dL), glycosylated hemoglobin (-0.18 %), low-density lipoprotein cholesterol (-8.5 mg/dL) and triglycerides (-20.3 mg/dL) were reduced significantly, high-density lipoprotein was increased by 0.18 %, while potassium and creatinine levels remained stable. The proportion of patients with adverse drug reactions (ADRs) was 1.3 % (n = 61 events in 45 patients). There were ten serious ADRs in eight patients; four patients died without causal relationship to study drug.

CONCLUSIONS

The results confirm previous randomized clinical trial data supporting the effectiveness, tolerability, and safety of this fixed-dose combination in an unselected patient population with high cardiovascular risk.