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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. Results Titrated Patch Doses The mean patch dose employed (ie, that dose required to achieve at least a 2-minute increase in exercise time 1 hour after application in a patient receiving long-term ISDN treatment) was 125 sq cm. Individual doses were 60 sq cm, 80 sq cm (three patients), 140 sq cm (two patients), 200 sq cm, and 220 sq cm. Exercise Time to Angina Performance during placebo treatment was relatively constant throughout the day with only a small mean increase from 259 ± 18 s to 278 ± 19 s in exercise time to angina 1 hour after patch application (Fig 1 and Table 1). (Since patients did not return to the laboratory on the morning after the placebo day, an arbitrary “24-hour” value was used by averaging the 8 am control exercise test values for the 2 days for each patient.) Figure 1. Mean duration of exercise to angina at different hours during the placebo and nitroglycerin patch days. Patches were applied after the 8 am bout. See Table 1 for p values. Table 1—Mean Values jor Exercise Duration on Placebo and Nitroglycerin Patch Days (Seconds)

Time	Placebo	Nitroglycerin  Patch	P
8 am (baseline)	259 ±18	271 ± 16	0.4
9 AM	278 ± 19	480 ±47	0.0000
11 AM	234 ±10	398 ±34	0.0004
1 PM	260 ± 13	404 ±28	0.0002
2 PM	262 ±15	398 ±37	0.0004
4 PM	233 ± 14	310 ±26	0.0011
6 PM	219 ±10	330 ± 28	0.0000
7 PM	232 ±12	326 ±30	0.0008
8 am (+ 1 day)	274 ±16	326 ±35	0.2