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(Circulation. 1995;91:1368-1374.)
© 1995 American Heart Association, Inc.

Articles

Intermittent Transdermal Nitroglycerin Therapy in Angina Pectoris

Clinically Effective Without Tolerance or Rebound

John O. Parker, MD, FACC; Mark H. Amies, MB, ChB; Ron W. Hawkinson, MS; James M. Heilman, BS; Andrina J. Hougham, BA; Mark C. Vollmer, BS; Richard R. Wilson, MD; and the Minitran Efficacy Study Group

From Queen's University (J.O.P.), Kingston, Ontario, Canada, and 3M Pharmaceuticals, St Paul, Minn.

Correspondence to John O. Parker, MD, Cardiovascular Lab–Kidd 3, Kingston General Hospital, 76 Stuart St, Kingston, Ontario, Canada K7L 2V7.

Background The objectives of this study were to assess the antianginal and anti-ischemic effects of three dose levels of transdermal nitroglycerin patches applied for 12 hours daily for 30 days. The study also assessed the development of tolerance and rebound. Intermittent transdermal nitroglycerin therapy with a patch-free period of 10 to 12 hours each day has documented clinical benefits during the period of patch application, but studies have failed to clearly document prolonged exercise duration for the entire period of patch application. This study was designed to evaluate the efficacy and duration of action of a range of doses of nitroglycerin. The study also permitted the assessment of the maintenance of initial effects, the development of tolerance, and the presence of rebound.

Methods and Results This study was a multicenter, randomized, double-blind, placebo-controlled parallel design trial with treadmill exercise tests at days 0, 1, 7, 15, and 30. Tests were carried out up to 12 hours after patch application. There was a statistically significant treatment effect with increases in treadmill walking time to moderate angina in each nitroglycerin patch group compared with placebo at various time points up to 12 hours throughout the 30-day study period. Secondary efficacy parameters, including the consistent increase in time to 1-mm ST-segment depression, supported the primary efficacy results. There was no evidence of tolerance or rebound.

Conclusions Intermittent transdermal nitroglycerin therapy increases exercise duration and maintains anti-ischemic effects for 12 hours after patch application, throughout 30 days of therapy, without significant evidence of nitrate tolerance or rebound phenomena.

Key Words: angina • nitroglycerin • exercise

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