The efficacy and safety of nisoldipine CC and lisinopril were compared in 278 patients with mild to moderate systemic hypertension in a double-blind, placebo run-in trial. Patients were randomized to nisoldipine CC or lisinopril for 8 weeks to achieve a trough sitting diastolic blood pressure (BP)< or = 90 mmHg. Responders were maintained on their optimal dose for a further 8 weeks. Nonresponders were switched to combination therapy and treated for 8 weeks. Twenty-four-hour ambulatory BP monitoring (ABPM) was carried out during placebo and monotherapy. The responder rate of 73.8% with nisoldipine CC after 8 weeks was greater than 56.1% with lisinopril (p = 0.007). The responder rate with combination therapy was 61%. ABPM showed that both nisoldipine CC and lisinopril produced constant blood pressure lowering effects over the 24-hour period and maintained circadian rhythm. Adverse effects were more frequent with nisoldipine CC (headache and peripheral edema) than with lisinopril (cough) monotherapy. Nisoldipine CC monotherapy was at least as effective as lisinopril monotherapy in the management of mild to moderate hypertension. Both agents were well tolerated. Combination therapy with nisoldipine CC and lisinopril was effective and well tolerated in patients with blood pressure not controlled by monotherapy alone.

Nisoldipine is a second-generation dihydropyridine calcium channel blocker (CCB). It is the most vascular selective of the currently available CCBs, and thus has the capacity to lower blood pressure without affecting the functioning of the myocardium and skeletal muscle, and without producing any negative inotropic effects. Nisoldipine coat core (CC) is an extended-release formulation that allows nisoldipine to be released gradually over 24 hours, minimizing fluctuations in plasma concentration and providing a good trough/peak ratio. It has a slow onset and long duration of action, and ambulatory blood pressure monitoring has demonstrated that its antihypertensive effect is maintained over 24 hours with no evidence of reflex tachycardia, hypotension, or sympathetic neurohormonal activation and no effects on circadian variation. Studies in patients with hypertension have shown that nisoldipine CC provides reductions in blood pressure that are at least equivalent to those seen with diuretics, beta-blockers, angiotensin-converting enzyme inhibitors, and other CCBs, without deleterious effects on metabolic parameters. In particular, it has been found to be effective in elderly patients and in black patients with severe hypertension. The DEFIANT studies have demonstrated that nisoldipine CC improves cardiac function and exercise tolerance in patients recovering from acute myocardial infarction, without increasing the risk of mortality compared with placebo. It also improves exercise performance in patients with stable angina pectoris. Nisoldipine CC is well tolerated in all groups of patients, with the most frequently reported side effects being headache and peripheral edema, which are usually mild and transient.

SUMMARYThis study compared the efficacy and tolerability of nisoldipine coat core (CC) 10‐40 mg o.d. and hydrochlorothiazide (HCTZ) 25‐50 mg o.d. Patients with mild‐to‐moderate essential hypertension received either nisoldipine CC 10 mg o.d. or HCTZ 25 mg o.d. Treatment was titrated at two‐weekly intervals as necessary. The primary efficacy endpoint was a defined reduction in diastolic blood pressure (DBP). Response rates were similar for both the nisoldipine CC‐ and HCTZ‐treated groups (74% and 70%, respectively). Secondary efficacy endpoints were reductions in both diastolic and systolic blood pressures (SBP). At treatment endpoint, the change from baseline in SBP was 16.2 mmHg for the nisoldipine CC group and 14.9 mmHg for the HCTZ group. Both drugs were well tolerated, and adverse events were generally minor and typical of these antihypertensive agents. Drug‐related adverse events were greater in the nisoldipine CC‐ than the HCTZ‐treated patients (50% and 37%, respectively). Nisoldipine CC was shown to demonstrate antihypertensive efficacy similar to HCTZ in the treatment of mild‐to‐moderate hypertension.