Author + information
- Received August 19, 1991
- Revision received December 5, 1991
- Accepted January 6, 1992
- Published online June 1, 1992.
- William W Parmley, MD, FACCa,∗,
- Richard W Nesto, MD, FACCb,
- Bramah N Singh, MD, PhD, FACCc,
- John Deanfield, MRCPd,
- Sidney O Gottlieb, MD, FACCs,
- The N-CAP Study Group∥
- ↵∗Address for reprints: William W. Parmley, MD, Professor of Medicine, University of California at San Francisco, San Francisco, California 94132.
The Nifedipine Gastro-Intestinal Therapeutic System (GITS) Circadian Anti-ischemia Program (N-CAP) was designed to test the effect of nifedipine GITS as monotherapy or in combination with a beta-adrenergic blocking agent on the circadian pattern of angina and silent ischemia in patients with chronic stable angina. At 118 sites in the United States, 1,174 patients were screened for entry into this study. To be eligible for participation patients were required to have at least two episodes of angina a week and at least two episodes of myocardial ischemia during 48-h ambulatory electrocardiographic (ECG) monitoring during the baseline placebo period. A total of 207 patients completed all phases of the study. Beta-blockers were continued in those patients already receiving them.
In this 7- to 10-week single-blind placebo withdrawal study, a 1-week placebo run-in was followed by up to 5 weeks of single-bund titration with nifedipine GITS, a 4-week efficacy phase with an established dose and a final single-blind 2-week placebo withdrawal period. Ambulatory ECG monitoring was performed at the end of each placebo phase and at the end of the efficacy phase with a digital monitoring device that was validated in a pilot study.
Overall, nifedipine GITS significantly reduced the weekly number of anginal episodes from 5.7 to 1.8 (p = 0.0001) and the number of ischemic events from 7.3 to 4 (p = 0.0001) reported during the 48-h monitoring periods, with a significant increase in both during the placebo withdrawal period. The baseline circadian pattern of ischemia showed an early morning peak and a secondary peak in the afternoon. Nifedipine GITS significantly reduced ischemia during the 48-h period when administered as monotherapy or in combination with a beta-blocker. Patients were also randomized to receive nifedipine GITS in either a morning or an evening dose. The two regimens resulted in equal anti-ischemic benefit. The primary side effect of nifedipine GITS was edema, which was dose related.
In summary, nifedipine GITS reduced the number of anginal and ischemic episodes when given alone or in combination with a beta-blocker. Nifedipine GITS had a sustained effect: a single daily dose was effective over 24 h regardless of whether it was administered in the morning or evening. This study also suggests that combination therapy with nifedipine GITS and a beta-blocker is especially efficacious in reducing ischemia.
- Received August 19, 1991.
- Revision received December 5, 1991.
- Accepted January 6, 1992.