Abstract
Background: Trapidil is an inhibitor of phosphodiesterase I‐IV with resulting positive lusitropic, vasodilating, and antiplatelet effects.
Hypothesis: This study was undertaken to compare the antianginal efficacy of trapidil with that of isosorbide dinitrate (ISDN) in patients with stable angina pectoris.
Methods: We studied 95 patients with stable angina pectoris who were randomized into a double‐blind parallel group study with either oral trapidil or ISDN. After a 1‐week run‐in period and a 2‐week wash‐out phase, the patients received either trapidil 200 mg t.i.d. (n = 48) or ISDN 20 mg t.i.d. (n = 47) for 12 weeks. All antianginal medication, except sublingual glyceryl trinitrate (GTN), was discontinued during the study. Patients underwent an exercise electrocardiogram on an ergometer bicycle according to a modified Bruce protocol before and at 6 and 12 weeks during treatment.
Results: The workload capacity increased from 583 ± 281 W‐min before treatment to 833 ± 444 W‐min after 12 weeks of treatment in the trapidil group (p<0.01) and from 555 ± 276 W‐min to 827 ± 361 W‐min in the ISDN group (p<0.01). The anginal attacks per week as well as the use of GTN decreased significantly in both groups. After 12 weeks of therapy, the cumulative ST‐segment depression during exercise decreased by 67% in the trapidil patients and by 23% in the ISDN patients. Compared with baseline, the double product at the 75 W level was reduced in both groups after 12 weeks of treatment. Blood pressure and heart rate at rest remained nearly unchanged. Overall, no statistical difference was found between the two study groups. The tolerability was good.
Conclusion: Oral trapidil therapy is safe and effective in stable angina pectoris and is equivalent to standard therapy with ISDN.
Keywords: trapidil, isosorbide dinitrate, angina pectoris, workload capacity
Full Text
The Full Text of this article is available as a PDF (587.1 KB).
References
- 1. Bethke T, Mehl H, Meyer W, Schmitz W, Scholz H, Thomas K, Wenzlaff H: Effects of the triazolopyrimidine trapidil on force of contraction, beating frequency and phosphodiesterase I‐1V activity in guinea‐pig hearts. Arzneimittelforschung 1991; 41: 461–468 [PubMed] [Google Scholar]
- 2. Di Donato M, Dabizzi RP, Maioli M, Fantini F: Acute haemodynamic effects of intravenous administration of trapidil in man. Arzneimittelforschung 1985; 35: 1295–1298 [PubMed] [Google Scholar]
- 3. Itoh S: Effekt der gleichzeitigen Verabreichung von Propranolol und Trapidil bei ischämischen Herzkrankheiten—Untersuchungen zur Arbeitstoleranzschwelle und zur Herzleistung. Junkan 1983; 8: 2–11 [Google Scholar]
- 4. Circo A, LoGiudice P, Chiaranda G, Mangiameli S, Monici Preti PA: Studio clinico sull'attivita antianginosa e antiaggregante piastrinica e sulla tollerabilità del trapidil in pazienti affetti da angina pectoris. Clin Eur 1991; 1: 33–43 [Google Scholar]
- 5. Nagakawa Y, Akedo Y, Orimo H, Yano H: Effect of the combination of antiplatelet agents in man: Combination of aspirin, trapidil, ticlopidine and dipyridamole. Thromb Res 1990; 60: 469–475 [DOI] [PubMed] [Google Scholar]
- 6. Liu MW, Roubin GS, Robinson KA, Black AJR, Hearn JA, Siegel RJ, King SB: Trapidil in preventing restenosis after balloon angioplasty in the atherosclerotic rabbit. Circulation 1990; 81: 1089–1093 [DOI] [PubMed] [Google Scholar]
- 7. Maresta A, Balducelli M, Cantini L, Casari A, Chioin R, Fabbri M, Fontanelli A, Monici Preti PA, Repetto S, De Servi S, Varani E, for the STARC investigators : Trapidil (triazolopyrimidine), a platelet‐derived growth factor antagonist, reduces restenosis after percutaneous transluminal coronary angioplasty. Results of the randomized, double‐blind STARC study. Circulation 1994; 90: 2710–2715 [DOI] [PubMed] [Google Scholar]
- 8. Nishikawa H, Ono N, Motoyasu M, Aoki T, Shimizu Y, Fukui A, Katuka Y, Nakano T: Preventive effects of trapidil (PDGF antagonist) on restenosis after PTCA. Circulation 1992; 86 (suppl): I‐53 [Google Scholar]
- 9. Okamoto S, Inden M, Setsuda M, Konishi T, Nakano T: Effects of trapidil (triazolopyrimidine), a platelet‐derived growth factor antagonist, in preventing restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1992; 123: 1439–1444 [DOI] [PubMed] [Google Scholar]
- 10. Reggiani S, Mattioli G: Effects of trapidil, a new inhibitor of thromboxane A2 synthetase, in patients with unstable angina. J Am Coll Cardiol 1992; 1 (suppl A): 238A [Google Scholar]
- 11. Kato K, Niinuma H, Kobayashi T, Kigawa R: Effekt von Trapidil auf Angina Pectoris—Untersuchung in Doppelbiindkreuzversuchen mit Propranolol. Kiso to Rinsho 1977; 11: 3221–3237 [Google Scholar]
- 12. LoGiudice P, Mesuraca L, Doria G, Musso R, Giustolisi R, Circo A, Lasagna G, Monici Preti PA: Trapidil: Efficacia terapeutica, tollerabilità ed effetti sull'aggregazione piastrinica in pazienti affetti da angina pectoris. Studio clinico controllato vs. verpamil. Basi Raz Ter 1989; 19: 43–53 [Google Scholar]
- 13. Martines G, Restori G: Trattamento antiaggregante della coronaropatia ischemica: Valutazione clinica controllata di trapidil vs. acido acetilsalicilico in pazienti con angina stabile. Terapia Mod 1990; 4: 307–312 [Google Scholar]
- 14. ESC Working Group on Exercise Physiology, Physiopathology and Electrocardiography : Guidelines for cardiac exercise testing. Eur Heart J 1993; 14: 969–988 [PubMed] [Google Scholar]
- 15. Flaherty JT: Nitrate tolerance. A review of the evidence. Drugs 1989; 37: 523–550 [DOI] [PubMed] [Google Scholar]
- 16. Kleist P, Klepzig H, Schmidt W, Kaltenbach M: Vergleich der anti‐ischämischen Wirksamkeit von dreimal täglich 20 mg Isosorbiddinitrat (ISDN) und einmal täglich 120 mg ISDN retard. Herz Kreislauf 1995; 27: 66–70 [Google Scholar]
- 17. Tauchert M, Jansen W, Metternich M, Osterspey A: Langzeittherapie mit Nitraten. Beziehung zwischen Dosierung und Toleranzentwicklung. Herz 1984; 9: 153–165 [PubMed] [Google Scholar]
- 18. Seabra‐Gomes R, Aleixo AM, Adao M, Machado FP, Mendes M, Bruges G, Palos JL: Comparison of the effects of a controlled‐release formulation of isosorbide‐5‐mononitrale and conventional isosorbide dinitrate on exercise performance in men with stable angina pectoris. Am J Cardiol 1990; 65: 1308–1312 [DOI] [PubMed] [Google Scholar]
- 19. Münzel T, Sayegh H, Freeman BA, Tarpey MM, Harrison DG: Evidence for enhanced vascular superoxide anion production in nitrate tolerance. A novel mechanism underlying tolerance and cross‐tolerance. J Clin Invest 1995; 95: 187–194 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. Lohr E: Therapie der ischämischen Herzkrankheit mit Trapidil. Anwendungsbeobachtung an 4014 Patienten in der ärztlichen Praxis. Fortschr Med 1994; 31: 446–450 [PubMed] [Google Scholar]