Dual blockade with candesartan cilexetil and lisinopril in hypertensive patients with diabetes mellitus: rationale and design

Background Blood pressure (BP) reduction is the key to risk reduction of cardiovascular disease or renal failure in hypertensive patients with diabetes mellitus. Inhibition of the renin-angiotensin system by an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin II receptor blocker (ARB) provides efficient BP reduction and renal protection in hypertensive diabetes patients. But, despite this, the recommended BP levels can be difficult to achieve and dual blockade therapy might be a possible way of obtaining efficient BP reduction in hypertensive patients with diabetes. Dual blockade treatment is based on a principle of obtaining the broadest and most efficient blockade of angiotensin II, by using the combination of an ACE-inhibitor and an ARB. Methods The Candesartan And Lisinopril Microalbuminuria (CALM II) study is a one centre, one observer, double-blind, randomised, active-controlled, parallel-group study, investigating the efficacy and tolerability of candesartan cilexetil in combination with lisinopril, compared with the maximum recommended dose of lisinopril in hypertensive patients with diabetes mellitus. The study design consists of two treatment arms with either 16 mg candesartan cilexetil or 20 mg lisinopril added to concomitant treatment with 20 mg lisinopril. It comprises 80 patients with a minimum of 35 patients in each group and statistical power of 90% to detect a difference in systolic BP reduction of 6.5 mmHg. Conclusion The CALM II study aims to investigate the effects of dual blockade on systolic BP, albuminuria, left ventricular mass and function, and retinopathy in hypertensive patients with diabetes mellitus.