Candesartan cilexetil/hydrochlorothiazide combination treatment versus high-dose candesartan cilexetil monotherapy in patients with mild to moderate cardiovascular risk (CHILI Triple T)

Background: Candesartan cilexetil has been shown to effectively reduce blood pressure and cardiovascular risk. Whether it is advantageous to combine candesartan cilexetil with low-dose hydrochlorothiazide (HCTZ) or uptitrate it in cases of insufficient blood pressure control has not been fully investigated under routine clinical conditions. Methods: CHILI Triple T is a prospective, noninterventional, observational study. Patients with uncontrolled hypertension and added cardiovascular risk received a fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg (combination therapy group) or high-dose monotherapy with candesartan cilexetil 32 mg (high-dose monotherapy group). Results: A total of 4600 patients with a mean age of 63.1 +/- 11.0 years, of which 44.7% were female, was included. The combination therapy group had 3337 patients, and the high-dose monotherapy group 1263 patients. Patients in both treatment groups were comparable with respect to age and gender, but patients receiving high-dose monotherapy had a slightly higher mean systolic blood pressure, more prior revascularizations, renal insufficiency, diabetic nephropathy, peripheral artery disease, and a lower ankle brachial index. The use of combination therapy resulted in a blood pressure reduction of -28.5 +/- 13.8/-14.2 +/- 9.4 mm Hg (P < 0.001 vs 160.2 +/- 13.3/94.5 +/- 8.2 mm Hg at baseline). The use of high-dose monotherapy reduced blood pressure by -29.73 +/- 15.3/-14.1 +/- 9.6 mm Hg (P < 0.001 vs 162.4 +/- 14.7/94.7 +/- 8.7 mm Hg at baseline). Differences in subgroups of patients defined by age, gender, body mass index, dyslipidemia, waist circumference, smoking, prior cardiovascular event, glomerular filtration rate, and microalbuminuria were minor, although partially significant. Tolerability was excellent, with only 28 out of 3358 patients (0.8%) in the combination therapy group and 15 out of 1273 patients (1.2%) in the high-dose monotherapy group experiencing any adverse event, of which one in each group was considered to be serious (<0.1%). Conclusions: Both the fixed-dose combination of candesartan cilexetil 16 mg and HCTZ 12.5 mg and high-dose monotherapy with candesartan 32 mg were highly effective in lowering blood pressure in patients at increased cardiovascular risk. Tolerability was excellent. The choice of either strategy therefore largely depends on the principal aim: blood pressure reduction with pronounced volume restriction or pronounced additional end-organ protection.