INTERMITTENT OR CONTINUOUS TRANSDERMAL NITROGLYCERIN - STILL AN ISSUE, OR IS THE CASE CLOSED

After a decade of controversy and debate, many experts have now conclu ded that continuous nitroglycerin patch treatment leads to complete to lerance development and therefore cannot be recommended for any angina patient. This conclusion is largely based on the disappointing result s of the large Transdermal Nitroglycerin Cooperative Study, in which c ontinuous patch treatment in doses of 15-105 mg daily failed to increa se exercise duration more than placebo after 2 and 8 weeks of treatmen t, However, other well-designed studies recently reported maintained e fficacy during continuous treatment, and the differences in results ha s remained unexplained. The disagreeing data may be better understood if certain facts are considered: (1) The cooperative study tested a pa tient population with a very low first-dose treatment response-only 34 seconds (or 10-12%) improvement compared with placebo. At the end of the study, 25% of the patients terminated exercise for reasons other t han angina, and a reduced nitrate responsiveness had developed, even i n the placebo group. (2) Patients who demonstrate a large first-dose n itrate responsiveness tend to be less susceptible to tolerance develop ment. (8) Even during continuous therapy, maintained efficacy is often observed in exercise tests done 2-5 hours after patch renewal, while typically no effect is seen at the end of the application period. Atte nuation of the initial effects is seen with all long-acting nitrate tr eatment regimens, but the degree of tolerance varies with the patient population, the efficacy parameter (exercise test vs. attack counts), the timing of the efficacy test, the patch dose, and whether or not ni trate-free (-low) intervals are used. In general, intermittent patch t herapy is superior to continuous therapy in improving exercise duratio n, but even continuous therapy may retain some effect. Rebound phenome na do occur but are clinically relevant only in a minority of the pati ents, Rebound phenomena are not a problem during continuous therapy, w hich therefore may be of value in patients with frequent and/or noctur nal angina attacks, Patients experiencing angina during exercise only and with low first-dose effects are likely to benefit more from interm ittent therapy, Doses of 0.6-0.8 mg/hr (15-20 mg/24 hr) are usually op timal, and the efficacy is comparable with that observed after oral ni trates.