Objective: Angiotensin-converting enzyme inhibitors plus dihydropyridine calcium channel blockers or low-dose thiazide diuretics are considered first-line therapies in hypertensive diabetic patients as glucose metabolism is not relevantly affected. Most diabetic patients require at least two different drug classes to achieve the recommended target blood pressure of 130/85 mmHg. This controlled clinical trial investigated the calcium channel blocker lercanidipine versus hydrochlorothiazide (HCTZ) as add-on in diabetic patients with uncontrolled hypertension on enalapril monotherapy.
Methods: Overall, 174 patients (18-80 years old, well-controlled diabetes type 1 or 2, mild to moderate hypertension) were included in a 2-week placebo run-in followed by 4 weeks on enalapril 20 mg. Subsequently, 135 non-responders (90 mmHg < or = mean sitting diastolic blood pressure < or = 109 mmHg) were randomized to 20 weeks of double-blind add-on therapy to enalapril with either lercanidipine 10 mg (n = 69) or HCTZ 12.5 mg (n = 66). The primary study objective was to prove non-inferiority of lercanidipine add-on versus HCTZ add-on in reducing sitting diastolic blood pressure; response rates and tolerability data were also observed.
Results: Both add-on treatments clearly decreased diastolic blood pressure to a greater extent than enalapril monotherapy (mean +/- SD changes at study end: lercanidipine, -9.3 mmHg; HCTZ, -7.4 mmHg); non-inferiority of lercanidipine versus HCTZ was formally proven. Blood pressure response rates reached 69.6% on enalapril plus lercanidipine as compared with 53.6% on enalapril plus HCTZ (difference between treatments, P > 0.05). Blood pressure of 130/85 mmHg or less was achieved in 30.4% of patients on lercanidipine add-on and in 23.2% of those randomized to HCTZ add-on (P > 0.05). Both treatment regimens were well tolerated.
Conclusion: Lercanidipine add-on showed comparable efficacy to HCTZ add-on in diabetic patients with hypertension badly controlled on angiotensin-converting enzyme inhibitor monotherapy. The blood pressure response rates seemed to be somewhat higher following enalapril plus lercanidipine than enalapril plus HCTZ.