Summary
Disagreeing results have been reported in the many studies on continuous treatment with nitroglycerin patches. The effects on exercise tolerance are partly studied at the end of a 24-hour application period, and partly examined only a few hours after patch renewal. The present meta-analysis estimates the overall efficacy of nitroglycerin patches in trials with and without concomitant antianginal therapy, and investigates if the treatment effect depends on the patch application time. A computed search (MEDLINE) identified 110 publications, of which 17 trials on nitrate patch monotherapy and six trials on combined therapy satisfied the inclusion criteria. Data on ‘exercise duration’ and ‘ST-segment depression’ were converted to a standardized treatment effect size d, and pooled to an overall treatment effect size d+. In tests 2–5 hours after patch renewal, moderate but significant effects of nitrate monotherapy were observed; d+ was 1.20 with regard to ‘ST-segment depression’ and 0.39 with regard to ‘exercise duration’ (both p<0.0001). In contrast, 24 hours after patch application, the values for d+ were 0.09 (not significant) and 0.36 (p<0.01), respectively. When adding the results from the six trials on combined therapy, d+ with regard to ‘exercise duration’ was reduced to 0.28 (p<0.0001) 2–5 hours after renewal and to 0.17 (p=0.04) after 24 hours. Thus, the efficacy of continuous nitroglycerin patch treatment is moderate but evident during exercise tests 2–5 hours after patch renewal; however, it is reduced after 24 hours of patch application.
Similar content being viewed by others
References
Parker JO, Fung HL. Transdermal nitroglycerin in angina pectoris. Am J Cardiol 1984;54:471–476.
Thadani U, Hamilton SF, Olson E, et al. Transdermal nitroglycerin patches in angina pectoris. Ann Intern Med 1986;105:485–492.
Crean PA, Ribeiro P, Crea F, et al. Failure of transdermal nitroglycerin to improve chronic stable angina: A randomized, placebo-controlled, double-blind, double crossover trial. Am Heart J 1984;108:1494–1500.
Greco R, D'Alterio D, Schiattarella M, et al. Efficacy of a new transdermal nitroglycerin patch (Deponit 10) for stable angina pectoris. Am J Cardiol 1988;61:44E-51E.
Scardi S, Pivotti F, Fonda F, et al. Effect of a new transdermal therapeutic system containing nitroglycerin on exercise capacity in patients with angina pectoris. Am Heart J 1985;110:546–551.
Thompson RH. The clinical use of transdermal delivery devices with nitroglycerin. Angiology 1983;34:23–31.
Müller P, Imhof PR, Burkart F, et al. Human pharmacological studies of a new transdermal system containing nitroglycerin. Eur J Clin Pharmacol 1982;22:473–480.
Chien YW. Pharmaceutical considerations of transdermal nitroglycerin delivery: The various approaches. Am Heart J 1984;108:207–216.
De Ponti F, Luca C, Pamparana F, et al. Bioavailability study of three transdermal nitroglycerin preparations in normal volunteers. Curr Ther Res 1989;46:111–120.
Charash B, Scheidt SS. The controversy of transdermal nitroglycerin: An update. Am Heart J 1986;112:207–215.
Barkve TF, Langseth-Manrique K, Bredesen JE, Gjesdal K. Increased uptake of transdermal glyceryl trinitrate during physical exercise and during high ambient temperature. Am Heart J 1986;112:537–541.
Weber S, de Lauture D, Rey E, et al. The effects of moderate sustained exercise on the pharmacokinetics of nitroglycerin. Br J Clin Pharmac 1987;23:103–105.
Lefebvre RA, Bogaert MG, Teirlynck O, et al. Influence of exercise on nitroglycerin plasma concentrations after transdermal application. Br J Clin Pharmac 1990;30:292–296.
Gjesdal K, Klemsdal TO, Rykke E, Bredesen JE. Transdermal nitrate therapy: Bioavailability during exercise increases transiently after the daily change of patch. Br J Clin Pharmac 1991;31:560–562.
Hedges LV, Olkin I. Statistical methods for meta-analysis. New York: Academic Press, 1985:75–175.
Carù B, Pirelli S, Ferratini M, et al. The effects on exercise tolerance of a new transdermal therapeutic system containing nitroglycerine in patients with stable angina pectoris. Eur Heart J 1988;9 (Suppl A):105–111.
Rezakovic DE, Pavicic L, Majacic M. A randomized placebo controlled, double-blind, crossover trial of transdermal nitroglycerin in stable angina pectoris. Eur Heart J 1988;9 (Suppl A):73–81.
Muiesan G, Agabiti-Rosei E, Muiesan L, et al. A multicenter trial of transdermal nitroglycerin in exercise-induced angina: Individual anti-anginal response after repeated administration. Am Heart J 1986;112:233–238.
Thompson R. Influence of transdermal nitrates on exercise capacity in patients with stable angina. Angiology 1986; 37:448–454.
Scardi S, Camerini F, Pandullo G, Pollavini P and the Collaborative Nitro Group. Efficacy of continuous and intermittent transdermal treatment with nitroglycerin in effort angina pectoris: A multicentric study. Int J Cardiol 1991; 32:241–248.
Frishman WH, Giles T, Greenberg S, et al. Sustained high-dose nitroglycerin transcutaneous patch therapy in angina pectoris: Evidence for attenuation of effect over time. J Clin Pharmacol 1989;29:1097–1105.
Luke R, Sharpe N, Coxon R. Transdermal nitroglycerin in angina pectoris: Efficacy of intermittent application. J Am Coll Cardiol 1987;10:642–646.
Greco R, Schiattarella M, Wolff S, et al. Long-term efficacy of nitroglycerin patch in stable angina pectoris. Am J Cardiol 1990;65:9J-15J.
Milliano PA, Koster RW, Bär FW, et al. Long-term efficacy of continuous and intermittent use of transdermal nitroglycerin in stable angina pectoris. Am J Cardiol 1991; 68:857–862.
Steering Committee, Transdermal Nitroglycerin Cooperative Study. Acute and chronic efficacy of continuous twentyfour-hour application of transdermal nitroglycerin. Am J Cardiol 1991;68:1263–1273.
Gibelli G, Negrini M, Bruno AM, et al. Chronic effects of transdermal nitroglycerin in stable angina pectoris: a within-patient, placebo-controlled study. Int J Clin Pharmacol Ther Toxicol 1989;27:436–441.
Sullivan M, Savvides M, Aboantoun S, et al. Failure of transdermal nitroglycerin to improve exercise capacity in patients with angina pectoris. J Am Coll Cardiol 1985;5: 1220–1223.
Reiniger G, Menke G, Boertz A, et al. Intervalltherapi zur effektiven Behandlung der Angina Pectoris mit Nitroglycerin-Pflastersystemen. Herz 1987;12:68–73.
Reiniger G, Rudolph W. Therapie der koronare Herzerkrankung mit Nitroglycerinpflastern. Herz 1985;10:305–311.
Reiniger G, Kraus F, Dirschinger J, et al. Hochdosierte transdermale Nitroglycerintherapie: Wirkungsverlust innerhalb von 24 Stunden? Herz 1985;10:157–162.
Reifart N, Bussmann WD. Placebo-kontrollierte Doppelblind-Studie zur antiischaemischen Wirksamheit und Wirkdauer von transdermalen Depotnitrat. Z Kardiol 1986;75 (Suppl 3):83–85.
Reichek N, Priest C, Zimrin D, et al. Antianginal effects of nitroglycerin patches. Am J Cardiol 1984;54:1–7.
Shell WE, Dobson D. Dissociation of exercise tolerance and total myocardial ischemic burden in chronic stable angina pectoris. Am J Cardiol 1990;66:42–48.
Colditz GA, Halvorsen KT, Goldhaber SZ. Randomized clinical trials of transdermal nitroglycerin systems for the treatment of angina: A meta-analysis. Am Heart J 1988;116: 174–180.
Zimrin D, Reichek N, Bogin KT, et al. Antianginal effects of intravenous nitroglycerin over 24 hours. Circulation 1988;77:1376–1384.
Thadani U, Fung H-L, Darke AC, Parker JO. Oral isosorbide dinitrate in angina pectoris. Comparison of duration of action and dose response relationship during acute and sustained therapy. Am J Cardiol 1982;49:411–417.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Klemsdal, T.O., Gjesdal, K. The effect of transdermal nitroglycerin on exercise tolerance in relation to patch application time—a meta-analysis. Cardiovasc Drug Ther 6, 641–649 (1992). https://doi.org/10.1007/BF00052566
Issue Date:
DOI: https://doi.org/10.1007/BF00052566