Comparison of Effects of Nisoldipine- Extended Release and Amlodipine in Patients With Systemic Hypertension and Chronic Stable Angina Pectoris Carl J. Pepine, MD, Rhonda M. Cooper-DeHoff, PharmD, Robert J. Weiss, MD, Michael Koren, MD, Neville Bittar, MD, Udho Thadani, MD, Margaret C. Minkwitz, PhD, Eric L. Michelson, MD, and Howard G. Hutchinson, MD, for the Comparative Efficacy and Safety of Nisoldipine and Amlodipine (CESNA-II) Study Investigators* The efficacy and safety of nisoldipine-extended release (ER) and amlodipine were compared in a 6-week multicenter, randomized, double-blind, double-dummy, parallel group, titration-to-effect trial in patients with stage 1 to 2 systemic hypertension (90 to 109 mm Hg diastolic blood pressure [BP]) and chronic stable angina pectoris. After a 3-week placebo run-in period, patients (n  120) were randomly assigned to active treatment with either nisoldipine-ER (20 to 40 mg) or amlodipine (5 to10 mg) once daily, titrated as necessary after 2 weeks to achieve diastolic BP <90 mm Hg. After 6 weeks, the mean reduction in systolic/diastolic BP from baseline was 15/13 mm Hg with nisoldipine-ER and 13/11 mm Hg with amlodipine (p  NS/p  NS). Both drugs resulted in similar BP responder rates (diastolic BP <90 mm Hg in 87% of patients who received nisoldip- ine-ER and 78% of patients on amlodipine, p  NS) and anti-ischemic responder rates (increasing exercise time >20% in 20% and 27%, respectively [p  NS], and in- creasing exercise time >60 seconds in 32% and 29% of patients, respectively [p  NS]. Also, after 6 weeks of active therapy, there was a similar mean increase in total exercise duration (23 seconds in the nisoldipine-ER group and 21 seconds in the amlodipine group, p  NS). Neither drug increased heart rate and both decreased frequency of anginal episodes. Adverse events were infrequent, and typically were vasodilator-related effects (including head- ache and peripheral edema) that occurred with somewhat higher incidence in the nisoldipine-ER group. Thus, nisol- dipine-ER and amlodipine provided comparable antihy- pertensive and anti-ischemic efficacy, and both were gen- erally well tolerated. 2003 by Excerpta Medica, Inc. (Am J Cardiol 2003;91:274 –279) A mong the calcium antagonists, long-acting sec- ond-generation dihydropyridines are potent vaso- dilators that are useful for monotherapy or in combi- nation with other classes of antihypertensives (e.g.,  blockers) to treat patients with systemic hypertension, as well as those with chronic stable angina pectoris. Nisoldipine-extended release (ER) is a second-gener- ation long-acting dihydropyridine suggested to have a 10-fold greater vascular selectivity than felodipine, nicardipine, and isradipine, and a 100-fold greater selectivity than nifedipine and amlodipine by in vitro tissue studies. 1 In addition, studies such as the Dopp- ler Echocardiography in Functional cardiac Insuffi- ciency: Assessment of Nisoldapine Therapy-II (DE- FIANT II) trial suggest that it is safe in patients with coronary heart disease. 2 However, randomized, con- trolled data directly comparing nisoldipine and other members of this class of drugs in hypertensive patients who have coexisting coronary heart disease are lim- ited. This study compares the efficacy and safety of nisoldipine-ER and amlodipine in patients with stage 1 to 2 hypertension and coronary heart disease using a randomized, controlled trial design. The efficacy of these agents on blood pressure (BP) and exercise parameters was also evaluated in a subset of patients during -1-adrenergic blockade with atenolol. METHODS Patient population: Patients with stage 1 to 2 hy- pertension (diastolic BP 90 to 109 mm Hg) and cor- onary heart disease were screened for eligibility. Cor- onary heart disease was defined as 1 of the follow- ing: documented myocardial infarction, coronary angiography demonstrating 60% diameter narrow- ing of a major nonrevascularized coronary artery, or an abnormal exercise stress test in conjunction with an abnormal myocardial imaging study (i.e., thallium, echocardiography, or radionuclide gated imaging). Patients were excluded if they had: symptomatic orthostatic hypotension; systolic BP 200 mm Hg or diastolic BP 110 mm Hg; sinus bradycardia (40 beats/min) or a heart rate at rest of 100 beats/min; stroke or myocardial infarction in the previous 3 From the University of Florida College of Medicine, Gainesville, Flor- ida; Androscoggin Cardiology Associates, Auburn, Maine; Jackson- ville Center for Clinical Research, Jacksonville, Florida; Gemini Scien- tific, Madison, Wisconsin; The University of Oklahoma Health Sci- ences Center, Oklahoma City, Oklahoma; and AstraZeneca LP, Wayne, Pennsylvania. This study was supported in part by a grant from AstraZeneca LP, Wayne, Pennsylvania. Manuscript received May 30, 2002; revised manuscript received and accepted September 20, 2002. Address for reprints: Carl J. Pepine, MD, University of Florida College of Medicine, PO Box 100277, Gainesville, Florida 32610- 0277. E-mail: pepincj@medicine.ufl.edu. *A list of investigators appears in the Appendix. 274 ©2003 by Excerpta Medica, Inc. All rights reserved. 0002-9149/03/$–see front matter The American Journal of Cardiology Vol. 91 February 1, 2003 PII S0002-9149(02)03154-5