OINTMENTS AND TRANSDERMAL NITROGLYCERIN PATCHES FOR STABLE ANGINA-PECTORIS

Nitroglycerin (NTG) ointment is used for the prophylaxis against angin a pectoris, but there are no data to support its effectiveness during long-term therapy. Continuous, once-daily application of isosorbide di nitrate cream produces tolerance with complete loss of efficacy within 1 week. Nitroglycerin patches are very popular and continuous once-da ily application is still claimed by some investigators to provide 24 h our antiischemic and antianginal efficacy. This claim is based on data from postmarketing studies in a very large number of patients and pla cebo-controlled studies in smaller groups of patients from Italy, Yugo slavia, Greece, and Germany. In contrast, studies from the United Stat es, Canada, England, and some centers in Germany have failed to show s uperiority of patches over placebo during continuous therapy. This con troversy was addressed by the NTG cooperative study group, in which a total of 562 patients who were responders to sublingual nitroglycerin were studied. Patients received either placebo or NTG patches deliveri ng low (15-30 mg/24 hr), moderate (45-60 mg/24 hr), or large (75 and 1 05 mg/24 hr) amounts of NTG. Four hours after the initial application, NTG patches increased exercise duration compared to placebo, but this beneficial effect had disappeared by 24 hours. Furthermore, after 8 w eeks of continuous therapy, none of the NTG patches were superior to p lacebo, whether patients were or were not taking concomitant beta-bloc kers. Therefore, current opinion is that continous therapy with NTG pa tches produces pharmacologic tolerance acid is ineffective. Pharmacolo gic tolerance can be minimized when patches are applied every morning and removed after 10-12 hours at night. However, patches delivering > 15 mg NTG/24 hr are required to maintain an increased exercise duratio n for up to hour 8 after the patch application. Intermittent therapy w ith patches, however, may lead to rebound nocturnal angina in some pat ients. Also, intermittent therapy with patches has been associated wit h worsening of exercise performance in the morning prior to the patch renewal, compared to therapy with placebo patches. This has been refer red to as the zero-hour effect and probably represents a rebound pheno menon following nitrate withdrawal. Patients experiencing either noctu rnal or early morning angina during intermittent therapy with patches should either be switched to oral long-acting nitrates or should in ad dition be treated with a beta-blocker, provided there are no contraind ications to beta-blocker treatment.