Category Archives: Nitroglycerin Patches

Representativeness of our Subjects Our subjects obviously were highly selected by the time they were entered into the definitive trial. Thus, one must ask whether our results can be extrapolated to the general population of patients with angina pectoris. The purpose of our study was not to evaluate the antianginal effectiveness of nitroglycerin patches for the large population of patients with chest pain thought to be anginal, or even for an unselected population of patients with unequivocal exercise-induced angina. It was rather to evaluate the potential effectiveness of the nitroglycerin patch per se as an antianginal agent, and as such required a be possible set of clinical circumstances. Namely, in a dition to being cooperative research subjects with stable, reproducible angina, the patients had to be e ccellent nitrate responders, free of nitrate-induced ide effects, and able to maintain at least some degree of nitrate responsiveness during long-term nitrate therapy. As such, our patients should be thought of as models for the best that can be achieved with nifhite-patch therapy, rather than representativ es for all patients with angina. (more…)

Several studies have suggested that the problem of continued patch effectiveness during long-term use could he overcome by means of an overnight patch-free interval. We believe that these studies are marred by the use of inadequate patch doses and too short an observation period of only one week during “long-term” patch application. An additional study involving more than 2(X) patients used patch doses of 10 to 40 sq cm for 4 weeks with a 12-hour on, 12-hour off regimen. The increases in exercise time compared with placebo were very small —15 to 30 s, were statistically significant only for the higher doses, and had practically disappeared by the end of the 4-week treatment period. A study monitoring the effect of nitroglycerin patches on ambulatory episodes of ST-segment depression found loss of effect by the second day despite a 12-hour overnight patch-free interval. (more…)

Thadani et al found a decreased amplitude and duration of the antianginal response to ISDN after 2 weeks of 4 times daily therapy, even though the last dose was taken at 8 pm and the first dose was taken at 8 am. In clinical practice, patients are up-titrated; failure to do so during a study of a nitrate administered long term is likely to lead to erroneous conclusions. (more…)

We believe that none of these methods is satisfactory. Fall in blood pressure or rise in heart rate by no means guarantees an antianginal effect, and 10 mm Hg or 10 bpm are less than the changes we observed w ith an optimal dose. Furthermore, in our opinion, patients who develop nitrate headache are not only unsuitable for a double-blind study, but they are also unacceptable for a dose titration study that seeks to determine the magnitude and duration of effect of a nitrate preparation administered in a pharmacologically optimal dose. Studies monitoring wedge pressure in congestive heart failure as the parameter for dose titration of nitroglycerin patch have employed doses of 64 sq cm and 120 sq cm to obtain an optimal therapeutic effect. Doses of 60 to 120 sq cm (mean, 104 sq cm) were found effective in reducing ischemic episodes detected by ambulatory electrocardiographic monitoring. (more…)

Discussion Batch Dose The doses that we found necessary (mean, 125 sq cm) to produce a day-long antianginal effect are far greater than those generally used in clinical practice, and much greater than those used in most studies. We believe strongly, however, that the rigorous, exercise test-based method of dose titration in patients already taking ISDN on a long-term basis indicates that such “high” doses are, in fact, the doses necessary to obtain the desired long-term effect from nitroglycerin patches. (more…)

There was a marked increase in exercise time 1 hour after active nitroglycerin patch application from 271 ±16 s to 480 ±47 s (p<0.001). This increase diminished somewhat by 3 hours after patch application, but thereafter there was a continuous and relatively constant superiority of performance compared with the placebo day, through the 7 pm test. Mean exercise performance at 24 hours was better than control and placebo values; however, there was a dichotomy in patient performance. Four patients showed no improvement over placebo ( + 6, —20, + 29, and —35 s), whereas the other four patients showed significant improvement (+ 130, +92, +157, and + 64 s). (more…)

Statistical Methots Differences between group mean exercise test variables for tests conducted at the same hour on the different study days or between different hours on the same day were compared by means of paired t tests after the performance of an analysis of variance. An adjusted p value was utilized to indicate statistical significance at the 0.05 level when multiple comparisons were made. Means ±SEM are given. Ethics The research nature of the study was explained to each patient, and informed consent was obtained. The study was approved by the institutional committee on human experimentation. (more…)

Administration of the treatments was double blind. Drug administration was at 8 am, and exercise bouts to angina were carried out at 9 am, 11 am, 1 pm, 2 pm, 4 pm, 6 pm, and at 7 pm. The patient then took his second daily dose of propranolol and went home. After the 9 am exercise, patients had a snack, and after the 2 pm test, patients ate lunch. By the end of each of the trial days, it was clear, based on the patient’s exercise performance during the day, whether the patient had received active nitroglycerin patch or placebo. On the day that the patient had received the nitroglycerin patch, he was invited to return to the lalxmitory the following morning for a single-blind test 24 hours after patch application. There was always at least a 10-day interval between trial days, and the study was completed within 8 to 12 days. During the whole period, except for the study days, patients took their usual dose of ISDN three times daily. (more…)

In two patients, we continued dose increments until responses were eventually obtained with doses of 200 and 220 sq cm. Failure to respond to the single-blind administration of placebo patches was a requirement for a patient to be considered to have had an adequate response to nitroglycerin patches. Definitive Trial The definitive trial involved the double-blind comparison of the day-long antianginal effectiveness ot placelx) and nitroglycerin patches in the eight patients who had undergone a mean of 26 (range, nine to 40) exercise bouts to angina during the preparatory phases of the study. (more…)

Once an adequate response to a given dose of ISDN was obtained, the patient was instructed to take that dose three times daily and he was retested in 2 weeks. If there was no longer at least a 2-minute increase in exercise time following single administration of the same dose, a larger dose was tested, and if effective, it was administered for 2 weeks three times daily. To continue onto the next phase of the study, a patient had to demonstrate continued responsiveness following 2 weeks of ISDN administration. We generally stopped titration if there was primary or secondary failure to respond after the single dose had been increased to 40 mg, although one patient s condition eventually stabilized with a 60-mg dose. (more…)