EFFECTS OF INTERMITTENT TRANSDERMAL NITROGLYCERIN ON OCCURRENCE OF ISCHEMIA AFTER PATCH REMOVAL - RESULTS OF THE SECOND TRANSDERMAL INTERMITTENT DOSING EVALUATION STUDY (TIDES-II)

Objectives. We sought to evaluate the effects of intermittent transder mal nitroglycerin (TD-NTG) on the occurrence of ischemia during patch off hours in patients with stable angina pectoris receiving a beta-adr energic blocking agent or calcium antagonist, or both. Background. The current recommendations for the use of intermittent TD-NTG may be ass ociated with the occurrence of rebound ischemia. Methods. This was a m ulticenter, randomized, double-blind, placebo-controlled, crossover tr ial with three study periods. Tolerability to TD-NTG was assessed in P eriod I. Seventy-two patients were assigned to receive either double-b lind transdermal placebo or maximally tolerated TD NTG for 2 weeks (Pe riod II) and were then crossed over to the alternative treatment for a nother 2 weeks (Period III). The patients were instructed to apply med ication daily at 8 AM, to remove it at 10 PM and to note symptoms and sublingual nitroglycerin (SL-NTG) use in a diary. The occurrence of is chemia was assessed from patient-perceived angina, symptom limited exe rcise treadmill test (ETT) and 48-h ambulatory electrocardiographic (A ECG) monitoring. Results. Transdermal NTG (0.2 to 0.4 mg/h) significan tly reduced the magnitude of ST segment depression at angina onset dur ing ETT compared with placebo. Total angina frequency was not signific antly different between TD-NTG (mean [+/-SD] 3.2 +/- 4.2) and placebo (3.3 +/- 5.2). During patch-off hours, angina frequency increased with TD-NTG (1.1 +/- 2.1) compared with placebo (0.7 +/- 1.6) (p = 0.03). Similar trends for an increase in ischemia after TD NTG were also obse rved from AECG analyses. Specifically, ischemia frequency tended to be lower during patch-off hours for placebo than with TD-NTG (0.05 +/- 0 .09 vs. 0.08 +/- 0.20 episodes/h, respectively, p = 0.08), even though frequency of ischemia tended to be higher during patch-on hours for p lacebo than with TD-NTG (0.12 +/- 0.19 vs. 0.07 +/- 0.15 episodes/h, r espectively, p = 0.11). During placebo, ischemia frequency decreased 5 8% (patch-on to patch-off, p = 0.01) compared with a 14% increase with TD-NTG. These changes attenuate the usual circadian variation in isch emia. Conclusions. An increase in ischemia frequency during patch-off hours after use of intermittent TD-NTG was perceived by patients, and this subjective finding was supported by a corresponding trend for AEC G ischemia to increase during these same hours. (C) 1997 by the Americ an College of Cardiology.