Sustained antianginal efficacy of transdermal nitroglycerin patches using an overnight 10-hour nitrate-free interval.

The antianginal efficacy of the transdermal nitroglycerin patch may be limited by the rapid development of tolerance during uninterrupted exposure. To address this problem, we investigated the role of intermittent therapy was investigated, using a daily nitroglycerin patch-free interval in 13 patients with chronic stable angina. Concomitant antianginal medications were permitted. Entry criteria required reproducible exercise times to both onset of angina and 1 mm of ST-segment depression. In each patient the highest tolerated nitroglycerin patch dose was determined by a dose-titration phase, which was then used in a double-blind crossover trial comprising 2 randomized treatment arms: 1 week of active nitroglycerin patch and 1 week of matching placebo. All patches were worn only from 8 A.M. to 10 P.M. daily. Exercise testing was repeated before patch application and then 4 and 8 hours after application on both the first and the last day of each treatment arm. Eleven patients completed the randomized crossover phase. Exercise time to the onset of angina and to the onset of 1 mm of ST-segment depression was significantly prolonged during the first day of therapy at both 4 and 8 hours after active nitroglycerin patch application compared with placebo (p less than 0.01). During sustained use, the benefit at 4 and 8 hours after nitroglycerin patch application was still evident (p less than 0.001 and p less than 0.05, respectively). No evidence of a overnight rebound or withdrawal phenomenon was observed by history or by ambulatory Holter monitoring calibrated for ST-segment analysis.(ABSTRACT TRUNCATED AT 250 WORDS)

Recurrent early ischemic events after thrombolysis for acute myocardial infarction.

Myocardium salvaged by early thrombolysis and then perfused through a residual stenosis may be at risk for ischemic events. To investigate this possibility, the short-term (2-week) clinical course of 81 consecutive patients managed within a randomized intracoronary thrombolysis trial was reviewed. All patients underwent coronary angiography within 5 hours of symptoms of acute myocardial infarction and were stratified into the following 3 outcome groups: patients with initially subtotal occlusion (subtotal group, n = 17), those with initial total occlusion and infarct artery reperfusion (reperfused group, n = 24) and those with continued infarct artery occlusion (occluded group, n = 40). Recurrent ischemic events were defined as spontaneous typical angina, provokable angina on predischarge exercise testing, and reinfarction. Eleven of 17 patients (65%) in the subtotal and 11 of 23 patients (48%) in the reperfused groups had an ischemic event (difference not significant). In contrast, 4 of 37 patients (11%) with occlusion had an ischemic event (p less than 0.01 compared with patients in the subtotal or reperfused groups). Four patients were excluded because of early (within 72 hours) elective coronary bypass surgery or death from pump failure. To eliminate the impact of multivessel coronary artery disease (CAD), 39 patients with 1-vessel CAD were analyzed separately. Five of 9 patients (56%) in the subtotal group, 3 of 10 (30%) in the reperfused group and only 2 of 20 (10%) in the occluded group had an ischemic event. These observations suggest the need for a more definitive revascularization strategy for acute myocardial infarction.