title: Efficacy, safety and duration of nitrate-free interval to prevent tolerance to transdermal nitroglycerin in effort angina.
abstract: The magnitude of tolerance to the anti-anginal efficacy of transdermal nitroglycerin and the efficacy and safety of short (4 h) and long (10 h) nitrate-free intervals for its prevention, were investigated in a randomized, double-blind, placebo-controlled crossover trial of 4 week-long treatment regimens: placebo, continuous therapy with a 50 mg patch (10 mg.24 h-1), and 4 h and 10 h nitrate-free periods. Only patients showing greater than 1 min increase in time to 1 mm ST depression after acute patch administration were eligible. Twelve men completed the study. One other anti-anginal medication (a beta-blocker in nine and calcium antagonist in two) was permitted in a constant dose throughout the study. Patients underwent exercise testing on days 1 and 7 of each treatment period, and 24 h ambulatory ECG monitoring on day 6. Compared to placebo, transdermal nitroglycerin on day 1 significantly improved time to 1 mm ST depression by 35%, and time to angina, exercise duration and maximal workload by 21%, 13% and 9% respectively. These improvements were totally lost after 7 days' continuous therapy, but completely maintained by a 10 h nitrate-free period (improvements of 35%, 25%, 16% and 11% respectively) but not by a 4 h nitrate-free period (non-significant improvements of 15%, 2%, 4% and 1% respectively). The differences between 10 and 4 h nitrate-free were significant for each end-point. Neither duration of ambulatory ischaemia, nor the proportion of patients experiencing greater than or equal to 5 min ischaemia during the scheduled nitrate-free interval differed between treatments.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Hallstrom Institute of Cardiology, University of Sydney, Royal Prince Alfred Hospital, Australia.
authors.forename: T
authors.initials: T
authors.lastname: Gumbrielle
authors.forename: S B
authors.initials: SB
authors.lastname: Freedman
authors.forename: L
authors.initials: L
authors.lastname: Fogarty
authors.forename: S
authors.initials: S
authors.lastname: Ogasawara
authors.forename: P
authors.initials: P
authors.lastname: Sobb
authors.forename: D T
authors.initials: DT
authors.lastname: Kelly
mesh_terms: D000279:Administration, Cutaneous; D000787:Angina Pectoris / Q000188:drug therapy* / Q000209:etiology; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology; D004562:Electrocardiography; D005080:Exercise Test; D006801:Humans; D008297:Male; D005996:Nitroglycerin / Q000008:administration & dosage*; D005082:Physical Exertion; D010919:Placebos; D013997:Time Factors
chemical_list: D010919:Placebos; D005996:Nitroglycerin