Candesartan cilexetil/hydrochlorothiazide treatment in high-risk patients with type 2 diabetes mellitus and microalbuminuria: the CHILI T2D study

Abstract

Background: Arterial hypertension complicated by the presence of diabetes mellitus and microalbuminuria is a particularly hazardous risk-factor combination. Blockers of the renin-angiotensin system have been shown to be beneficial with respect to these risk factors in randomized clinical trials.

Objectives: To provide proof of effectiveness for a fixed-dose combination such as candesartan cilexetil 16 mg/hydrochlorothiazide (HCTZ) 12.5 mg in clinical practice within the context of a variety of concomitant diseases and medications.

Methods: CHILI T2D was a non-interventional, open-label, non-controlled, multicentre study in clinical practice that evaluated 4110 patients with type 2 diabetes, uncontrolled hypertension and microalbuminuria who were being prescribed a fixed-dose combination of candesartan cilexetil 16 mg/HCTZ 12.5 mg (Blopress). Documented outcomes included blood pressure (BP) reductions, metabolic changes, changes in albuminuria, and adverse events throughout the 12-week treatment period.

Results: Patients had a mean +/- SD age of 64.0 +/- 10.3 years, 54.0% were male and the mean +/- SD body mass index was 29.6 +/- 5.8 kg/m2. Coronary heart disease (34.3%), diabetic neuropathy (23.8%), retinopathy (18.6%) and heart failure (20.2%) were frequent co-morbidities. The use of candesartan cilexetil 16 mg/HCTZ 12.5 mg in patients with a mean +/- SD baseline BP of 158.5 +/- 14.2/92.5 +/- 9.1 mmHg resulted in a substantial further reduction of office BP by a mean +/- SD of -27.1 +/- 14.4/-13.1 +/- 9.5 mmHg (p < 0.001). The reduction was particularly pronounced in patients with severe hypertension (mean reduction of -44.7/-19.9 mmHg). Glucose (glycosylated haemoglobin [HbA(1c)], fasting blood glucose) as well as lipid parameters (total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides) were significantly improved (p < 0.001). Microalbuminuria, indicative of renal and cardiovascular risk, was significantly reduced by 28.8% (p < 0.001). Tolerability was excellent with only 16 out of 4110 patients experiencing any adverse event, of which six were considered to be serious.

Conclusions: The fixed-dose combination of candesartan cilexetil 16 mg/HCTZ 12.5 mg is highly effective in lowering blood pressure in type 2 diabetic patients with all stages of hypertension and microalbuminuria. The data indicate that low-dose HCTZ can safely be added to an existing drug regimen in this patient group to increase the BP-lowering effect, without compromising tolerability and the favourable metabolic profile of candesartan cilexetil monotherapy.