Individual responses to transdermal nitrates after chronic administration in angina pectoris

The aim of this study was to investigate whether, and to which extent, sustained treatment with transdermal nitroglycerin plasters may lead to the development of tolerance in patients with effort-induced angina pectoris. Ten patients, all men, mean age 62.7 years, took part in a double-blind, cross-over, acute study, comparing the transdermal therapeutic system of nitroglycerin 10 mg/24 hours with placebo. Patients were then treated for 1 month with the active drug in single-blind condition, and finally they took part in a further acute study identical to the first. Cycloergometric exercise tests were carried out 4 hours after dosing. In comparison with placebo, the active drug significantly (P less than 0.01) increased ischaemic threshold (ST depression = 1 mm) after both acute (from 299 +- 92 to 413 +- 120 sec) and chronic treatment (416 +- 107 sec). The same results were obtained for exercise duration to peak exercise (acute study: from 336 +- 65 to 482 +- 90 sec; chronic treatment: 466 +- 118 sec). The final acute study confirmed the stability of angina, showing that the improvement in exercise tolerance after chronic treatment was entirely due to the pharmacological effect of the drug. In terms of single patient response to the active treatment, 7 of the 10 patients showed an improvement in exercise tolerance after both acute and chronic treatment, while in 3 patients no antianginal effect was observed. These results suggest that nitrate tolerance cannot be considered an inevitable finding in patients chronically treated with transdermal patches.