Individual responses to transdermal nitrates after chronic administration in angina pectoris

Scardi, S; Pandullo, Claudio; Pivotti, F; Ceschia, Giuliano; Pollavini, G.

doi:10.1016/0167-5273(88)90005-8

Cited by 4 publications

(3 citation statements)

References 23 publications

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“…The heterogeneity of the study populations and protocols is apparent when the first-dose effects are compared; some studies report only 10-12% (30-50 second) improvement in exercise duration [1,14,16], while others demonstrate two to three times that effect [15,[17][18][19]. It may therefore be misleading to compare the efficacy of different treatment regimens (i.e., continuous vs. intermittent, high doses vs. low doses, transdermal vs. oral nitrates) in studies performed in different patient populations.…”

Section: Different Study Populations and Nitrate Responsivenessmentioning

confidence: 99%

“…It may therefore be misleading to compare the efficacy of different treatment regimens (i.e., continuous vs. intermittent, high doses vs. low doses, transdermal vs. oral nitrates) in studies performed in different patient populations. A further point is that patients with a low initial treatment response appear to be more susceptible to tolerance development [17], and studies that report maintained efficacy typically also describe large first-dose effects [18][19][20]. Regrettably, there are few randomized comparisons of the different nitrate treatment regimens.…”

Section: Different Study Populations and Nitrate Responsivenessmentioning

confidence: 99%

“…Maintained efficacy has been observed 2-5 hours after patch renewal in studies using 0.4-0.8 mg/hr (10-20 mg/24 hr) [17][18][19][20]34,35,56]. Significant effects after 12-24 hours of application have not often been observed, but such were reported in trials with 0.4-0.8 mg/hr [25].…”

Section: Optimal Dosesmentioning

confidence: 99%

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Intermittent or continuous transdermal nitroglycerin: Still an issue, or Is the case closed?

Klemsdal

Gjesdal

1996

Cardiovasc Drug Ther

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After a decade of controversy and debate, many experts have now concluded that continuous nitroglycerin patch treatment leads to complete tolerance development and therefore cannot be recommended for any angina patient. This conclusion is largely based on the disappointing results of the large Transdermal Nitroglycerin Cooperative Study, in which continuous patch treatment in doses of 15-105 mg daily failed to increase exercise duration more than placebo after 2 and 8 weeks of treatment. However, other well-designed studies recently reported maintained efficacy during continuous treatment, and the differences in results has remained unexplained. The disagreeing data may be better understood if certain facts are considered: (1) The cooperative study tested a patient 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 than angina, and a reduced nitrate responsiveness had developed, even in the placebo group. (2) Patients who demonstrate a large first-dose nitrate responsiveness tend to be less susceptible to tolerance development. (3) 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. Attenuation of the initial effects is seen with all long-acting nitrate treatment 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 nitrate-free (-low) intervals are used. In general, intermittent patch therapy is superior to continuous therapy in improving exercise duration, but even continuous therapy may retain some effect. Rebound phenomena do occur but are clinically relevant only in a minority of the patients. Rebound phenomena are not a problem during continuous therapy, which therefore may be of value in patients with frequent and/or nocturnal angina attacks. Patients experiencing angina during exercise only and with low first-dose effects are likely to benefit more from intermittent therapy. Doses of 0.6-0.8 mg/hr (15-20 mg/24 hr) are usually optimal, and the efficacy is comparable with that observed after oral nitrates.

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