INTERMITTENT TRANSDERMAL NITRATES DO NOT IMPROVE ISCHEMIA IN PATIENTSTAKING BETA-BLOCKERS OR CALCIUM-ANTAGONISTS - POTENTIAL ROLE OF REBOUND ISCHEMIA DURING THE NITRATE-FREE PERIOD

Objectives. This study was conducted to determine whether rebound isch emia occurs during nitrate free periods with intermittent cutaneous ni troglycerin therapy in patients with angina pectoris who are receiving background antianginal therapy. Background. Rebound angina has been s uggested to be a complication of the nitrate free period with long-ter m cutaneous nitroglycerin therapy given intermittently to prevent tole rance. Methods. Fifty-two patients with stable effort angina taking ei ther a beta-adrenergic blocking agent (n = 25) or diltiazem (n = 22) o r their combination (n = 5) completed a randomized, double-blind, plac ebo controlled crossover study of cutaneous nitroglycerin patches (50 mg). Active or placebo patches were worn for 1 week applied at 8 AM an d removed at 10 PM to provide a 10-h daily nitrate-free (or placebo fr ee) period. During the last 48 h of each study phase, a Holter monitor was used to detect ischemia. Results. Only 31 patients experienced is chemia during either phase of the study (23 during the patch-off perio d). A total of 463 ischemic episodes were recorded: 246 during placebo and 217 during nitroglycerin (p = 0.8, for per patient comparison). T he majority (88%) of ischemic episodes were silent, Mean (+/-SEM) dura tion of ischemia during the total 48 h period was similar during activ e and placebo phases (35.5 +/- 15.0 min/24 h for active therapy vs. 29 .7 +/- 9.8 for placebo, p = 0.8). This was due to an increase in durat ion of ischemia with active therapy during the patch-off period (46.9 +/- 17.9 min/24 h for active therapy vs. 22.5 +/- 9.2 for placebo, p = 0.07) and a decrease during the patch-on period (27.5 +/- 14.0 min/24 h for active therapy vs. 34.5 +/- 11.0 min/24 h for placebo, p = 0.16 ). The pattern of diurnal distribution of ischemic episodes differed b etween active and placebo phases. During placebo there was a nadir in the incidence of ischemia in the overnight patch-off period, with a si gnificantly lower incidence between midnight and 6 AM (25 episodes) co mpared with the mean number of episodes during the three other 6-h per iods (73 episodes, p < 0.001). During the nitroglycerin patch off peri od, there was a loss of this overnight nadir, with the same incidence of ischemia between midnight and 6 AM (53 episodes) as the mean number of episodes for the three other 6-h periods (54 episodes). Conclusion s. The majority of patients taking background anti anginal therapy exp erienced no ischemia during the patch off period. In the 44% of patien ts with ischemia during this period, there was a nonsignificant increa se in the duration of ischemia with active therapy. Although this resu lt was statistically inconclusive, the change in the distribution of d iurnal ischemia offers suggestive evidence that rebound ischemia may b e a problem with regard to intermittent cutaneous nitroglycerin.