Nisoldipine CC and Lisinopril Alone or in Combination for Treatment of Mild to Moderate Systemic Hypertension Nisoldipine CC Therapy for Hypertension Terrence D. Ruddy 1 and J. George Fodor 2 , for the Canadian Nisoldipine CC Hypertension Trial Group * 1 Division of Cardiology and 2 Prevention and Rehabilitation Centre, University of Ottawa Heart Institute, Ottawa, Canada Summary. The efficacy and safety of nisoldipine CC and lisinopril were compared in 278 patients with mild to mod- erate 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) 90 mmHg. Responders were main- tained on their optimal dose for a further 8 weeks. Nonre- sponders 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 pro- duced 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) mono- therapy. Nisoldipine CC monotherapy was at least as effec- tive 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. Cardiovasc Drugs Ther 1997;11:581–590 Key Words. systemic hypertension, nisoldipine, lisinopril, ambulatory blood pressure monitoring The calcium channel antagonists are becoming widely used in systemic hypertension, either as monotherapy or in combination with other antihypertensive drugs [1–4]. In addition to their blood pressure (BP)–lower- ing effects, calcium channel antagonists may decrease symptoms of angina [4], improve impaired renal func- tion [5–7], regress left ventricular hypertrophy [8,9], and slow atherogenesis [10]. The first-generation cal- cium channel antagonists included nifedipine, vera- pamil, and diltiazem, and had cardiodepressent effects affecting conduction and contractility. The newer sec- ond-generation calcium channel antagonists, such as amlodipine, nisoldipine, and felodipine, have compara- tively greater affinity for vascular tissue than myocar- dium at therapeutic doses and lesser negative inotropic effects [4]. These second-generation calcium channel antagonists are well tolerated in patients with con- comitant disorders, such as asthma, heart failure, dia- betes, gout, and hyperlipidemia [4]. These second-gen- eration calcium antagonists are relatively free of drug interactions and can be combined with other antihy- pertensive agents [4,10]. Nisoldipine is a second-generation dihydropyridine and has potent peripheral and coronary vasodilating properties [11,12]. A newly developed coat-core (CC) controlled-release formulation of nisoldipine provides fairly constant blood levels with a once-daily dose [13]. Preliminary data have shown that nisoldipine CC is effective as monotherapy in the management of pa- tients with systemic hypertension [14]. Lisinopril is a once-a-day angiotensin-converting enzyme (ACE) in- hibitor and is effective and well tolerated as mono- therapy and in combination with other antihyperten- sive agents for the treatment of systemic hypertension [15,16]. The primary objective of this study was to compare the antihypertensive efficacy of once-daily nisoldipine CC in doses of 10, 20, and 40 mg versus once-daily lisinopril in doses of 5, 10, and 20 mg for the treatment of mild to moderate systemic hypertension. The secon- dary objectives were to compare the safety of once- daily nisoldipine CC versus once-daily lisinopril and to define the safety and effectiveness of nisoldipine CC in combination with lisinopril in patients not responding (diastolic BP 90 mmHg) to either nisoldipine CC or lisinopril monotherapy. The study was also intended to determine whether any resistance occurred after 16 * See the appendix for a list of participants. Address for correspondence: Dr. Terrence D. Ruddy, University of Ottawa Heart Institute, 1053 Carling Avenue, Ottawa, Ontario, Canada K1Y 4E9. Nisoldipine CC Therapy for Hypertension Received 10 October 1996; receipt/review time 5.3 months; ac- cepted in revised form 20 March 1997 581 Cardiovascular Drugs and Therapy 1997;11:581–590 © Kluwer Academic Publishers. Boston.