Copyright © 2000 by the European Society of Cardiology.
Randomized comparative trial of triflusal and aspirin following acute myocardial infarction
a Department of Cardiology, Hospital Universitario Virgen de la Macarena, Sevilla, Spain
b Department of Cardiology, Hospital Universitario de Getafe, Madrid, Spain
c Department of Cardiology, Hospital Vall D'Hebron, Barcelona, Spain
d Department of Cardiology, Hospital La Fe, Valencia, Spain
e Department of Cardiology, Hospital La Paz, Madrid, Spain
f Department of Cardiology, Hospital General, Valencia, Spain
g Department of Cardiology, Hospital Juan Canalejo, La Coruña, Spain
h Laboratorio de Bioestadística y Epidemiología, Facultad de Medicina, UAB, Barcelona, Spain
i Department of Cardiology, Hospital Torrecárdenas, Almería, Spain
j Department of Cardiology, Hospital Miguel Servet, Zaragoza, Spain
revised July 5, 1999; accepted July 21, 1999
Abstract
Aims To compare the efficacy and tolerability of the antiplatelet agent triflusal with aspirin in the prevention of cardiovascular events following acute myocardial infarction.
Methods and Results In this double-blind, multicentre, sequential design study, patients were randomized within 24h of acute myocardial infarction symptom onset to receive triflusal 600mg or aspirin 300mg once daily for 35 days. The primary end-point was death, non-fatal myocardial reinfarction or a non-fatal cerebrovascular event. The incidences of these individual outcomes and urgent revascularization were secondary end-points. The null hypothesis of no difference between treatments in the primary combined end-point was accepted with 80% power after recruiting 2124 validated patients (odds ratio (OR) for failure [95% confidence interval (CI)]: 0·882 [0·634–1·227]). Non-fatal cerebrovascular events were significantly less frequent with triflusal (OR [95% CI]: 0·364 [0·146–0·908];P=0·030). There was no significant difference between treatments for death (OR [95% CI]: 0·816 [0·564–1·179];P=0·278), non-fatal reinfarction (OR [95% CI]: 1·577 [0·873–2·848];P=0·131) or revascularization (OR [95% CI]: 0·864 [0·644–1·161];P=0·334). Overall, both drugs were well tolerated, although there was a trend towards fewer bleeding episodes with triflusal; significantly fewer central nervous system bleeding episodes were observed in triflusal-treated patients (0·27% vs 0·97%;P=0·033).
Conclusion Triflusal and aspirin have similar efficacy in preventing further cardiovascular events after acute myocardial infarction, but triflusal showed a more favourable safety profile. Triflusal significantly reduced the incidence of non-fatal cerebrovascular events compared with aspirin.
Key Words: Triflusal, aspirin, cardiovascular events, cerebrovascular events, acute myocardial infarction, sequential trial
f1 Correspondence: Professor J. M. Cruz-Fernández, Servicio de Cardiología, Hospital Universitario Virgen de la Macarena, Avda Dr. Fedriani, s/n, 41009 Sevilla, Spain.
References
- BMJ. 1994;308:81–106
[Abstract/Free Full Text] - Lancet. 1988;ii:349–360
- Patrono C. Aspirin as an antiplatelet drug. N Engl J Med. 1994;330:1287–1294
[Free Full Text] - Roderick PJ, Wilkes HC, Meade TW. The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials. Br J Clin Pharmacol. 1993;35:219–226[Web of Science][Medline]
- N Engl J Med. 1989;321:129–135[Abstract]
- Hirsh Jy, Dalen JE, Fuster V, Harker L, Patrono C, Roth GJ. Aspirin and other platelet active drugs: the relationship between dose, effectiveness, and side-effects. Chest. 1995;108:S247–257
- Boysen G, Boss AH, Odum N, Olsen JS. Prolongation of bleeding time and inhibition of platelet aggregation by low dose acetylsalicylic acid in patients with cerebrovascular disease. Stroke. 1984;15:241–243
[Abstract/Free Full Text] - de la Cruz JP, Villalobos MA, Garcia PJ. Effects of triflusal and its main metabolite HTB on platelet interaction with subendothelium in healthy volunteers. Eur J Clin Pharmacol. 1995;47:497–502[Web of Science][Medline]
- Albors M, Castellarnau C, Vila L, Sola J, Rutllant ML. Inhibition of thromboxane production and platelet function by triflusal in healthy volunteers. Rev Pharmacol Clin Exp. 1987;4:11–16
- de la Cruz JP, Mata JM, Sánchez de la Cuesta F. Triflusal versus aspirin on the inhibition of human platelet and vascular cyclooxygenase. Gen Pharmacol. 1992;23:297–300[Web of Science][Medline]
- García-Rafanell J, Ramis J, Gómez L, Forn J. Effect of triflusal and other salicylic acid derivatives on cyclic AMP levels in rat platelets. Arch Int Pharmacodyn Ther. 1986;284:155–165[Web of Science][Medline]
- Fernández de Arriba A, Cavalcanti F, Miralles A. Inhibition of cyclooxygenase-2 expression by 4-trifluoromethyl derivatives of salicylate, triflusal, and its deacetylated metabolite 2-hydroxy-4-trifluoromethylbenzoic acid. Mol Pharmacol. 1999;55:753–760
[Abstract/Free Full Text] - Bayón Y, Alonso A, Sánchez Crespo M. 4-trifluoromethyl derivatives of salicylate, triflusal and its main metabolite 2-hydroxy-4-trifluoromethylbenzoic acid are potent inhibitors of nuclear factor kB activation. Br J Pharmacol. 1999;126:1359–1366[CrossRef][Web of Science][Medline]
- Sánchez de Miguel L, del Prado Sierra M, López Farré A. Comparative effects of triflusal and acetylsalicylic acid on nitric oxide generation by human neutrophils. Eur J Pharmacol. 1998;343:57–65[CrossRef][Web of Science][Medline]
- Plaza L, López-Bescós L, Martín-Jadraque L. Protective effect of triflusal against acute myocardial infarction in patients with unstable angina: results of a Spanish multicentre trial. Grupo de Estudio del Triflusal en la Angina Inestable. Cardiology. 1993;82:388–398[Web of Science][Medline]
- Auteri A, Angaroni A, Borgatti E. Triflusal in the treatment of patients with chronic peripheral arteriopathy: multicentre double-blind clinical study vs. placebo. Int J Clin Pharmacol Res. 1995;15:57–63[Web of Science][Medline]
- Matías-Guiu L, Alvarez-Sabín J, Codina A. Comparative study of the effect of low-dosage acetylsalicylic acid and triflusal in the prevention of cardiovascular events among young adults with ischaemic cerebrovascular disease. Long-term outcome of young stroke patients. Rev Neurol. 1997;25:1669–1672[Web of Science][Medline]
- Smirne S, Ferini-Strambi L, Cucinotta D. Triflusal and prevention of cerebrovascular attacks: a double-blind clinical study vs ASA [abstract 53]. J Neurol. 1994;241:S130
- Putz P, Buyse H, Delvaux D. Triflusal versus acetylsalicylic acid: a double-blind study for the prophylaxis of deep vein thrombosis after hip surgery. Acta Chir Belg. 1991;91:269–276[Medline]
- Monreal M, Lafoz E, Roca J. Platelet count, antiplatelet therapy and pulmonary embolism—a prospective study in patients with hip surgery. Thromb Haemost. 1995;73:380–385[Web of Science][Medline]
- Masotti M, Tura A, Crexells C. Antiplatelet agents and their effect on complications during or soon after percutaneous transluminal coronary angioplasty. J Int Med Res. 1991;19:414–418[Web of Science][Medline]
- Guiteras P, Altamiras J, Aris A. Prevention of aorto-coronary vein-graft attrition with low-dose aspirin and triflusal, both associated with dipyridamole: a randomised, double-blind, placebo-controlled trial. Eur Heart J. 1989;10:159–167
[Abstract/Free Full Text] - Whitehead J. The design and analysis of sequential clinical trials. Chichester: Ellis Horwood; 1992.
- Whitehead J, Brunier H. PEST 2.0 Operating Manual. Reading: Reading University; 1989.
- Brunier H, Whitehead J. PEST 3.0 Operating Manual. Reading: Reading University; 1993.
- Marrugat J, Sala J, Masiá R. Mortality differences between men and women following first myocardial infarction. JAMA. 1998;280:1405–1409
[Abstract/Free Full Text]
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  C. Patrono, C. Baigent, J. Hirsh, and G. Roth Antiplatelet Drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 199S - 233S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. N. Salem, P. T. O'Gara, C. Madias, and S. G. Pauker Valvular and Structural Heart Disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 593S - 629S. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. G. Goodman, V. Menon, C. P. Cannon, G. Steg, E. M. Ohman, and R. A. Harrington Acute ST-Segment Elevation Myocardial Infarction: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition) Chest, June 1, 2008; 133(6_suppl): 708S - 775S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. Perez-Gomez, J. A. Iriarte, J. Zumalde, J. Berjon, A. Salvador, E. Alegria, M. P. Maluenda, S. Asenjo, R. Perez-Saldana, R. G. de la Torre, et al. Antithrombotic therapy in elderly patients with atrial fibrillation: effects and bleeding complications: a stratified analysis of the NASPEAF randomized trial Eur. Heart J., April 2, 2007; 28(8): 996 - 1003. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. Perez-Gomez, A. Salvador, J. Zumalde, J. A. Iriarte, J. Berjon, E. Alegria, C. Almeria, R. Bover, D. Herrera, C. Fernandez, et al. Effect of antithrombotic therapy in patients with mitral stenosis and atrial fibrillation: a sub-analysis of NASPEAF randomized trial Eur. Heart J., April 2, 2006; 27(8): 960 - 967. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. B. Gorelick and S. M. Weisman Risk of Hemorrhagic Stroke With Aspirin Use: An Update Stroke, August 1, 2005; 36(8): 1801 - 1807. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Whitehead, G. Cheng, V. Hachinski, and D. F. Cechetto Interaction Between a Rat Model of Cerebral Ischemia and {beta}-Amyloid Toxicity: II. Effects of Triflusal Stroke, August 1, 2005; 36(8): 1782 - 1789. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Aramendi, C.-A. Mestres, J. Martinez-Leon, V. Campos, G. Munoz, and C. Navas Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (trac): prospective, randomized, co-operative trial Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 854 - 860. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Borja Oral Antiplatelet Therapy JAMA, February 16, 2005; 293(7): 793 - 793. [Full Text] [PDF]
|
|
|
|
|
|
H. Tran and S. S. Anand Oral Antiplatelet Therapy--Reply JAMA, February 16, 2005; 293(7): 794 - 795. [Full Text] [PDF]
|
|
|
|
 |
|
 F. Perez-Gomez, E. Alegria, J. Berjon, J. A. Iriarte, J. Zumalde, A. Salvador, L. Mataix, and NASPEAF Investigators Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation: A randomized multicenter study J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1557 - 1566. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. H. Falk Reconsidering combined antiplatelet and anticoagulant therapy in atrial fibrillation J. Am. Coll. Cardiol., October 19, 2004; 44(8): 1567 - 1569. [Full Text] [PDF]
|
|
|
|
|
|
C. Patrono, B. Coller, G. A. FitzGerald, J. Hirsh, and G. Roth Platelet-Active Drugs: The Relationships Among Dose, Effectiveness, and Side Effects: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy Chest, September 1, 2004; 126(3_suppl): 234S - 264S. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Culebras, R. Rotta-Escalante, J. Vila, R. Dominguez, G. Abiusi, A. Famulari, R. Rey, L. Bauso-Tosselli, H. Gori, J. Ferrari, et al. Triflusal vs aspirin for prevention of cerebral infarction: A randomized stroke study Neurology, April 13, 2004; 62(7): 1073 - 1080. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. I. Aramendi, C. A. Mestres, V. Campos, J. Martinez-Leon, C. Pontes, G. Munoz, and J. C. Navas Triflusal versus oral anticoagulation for primary prevention of thromboembolism after bioprosthetic valve replacement (TRAC): rationale and design for a prospective, randomized, co-operative trial Interactive CardioVascular and Thoracic Surgery, June 1, 2003; 2(2): 170 - 174. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Matias-Guiu, J. M. Ferro, J. Alvarez-Sabin, F. Torres, M. D. Jimenez, A. Lago, T. Melo, and D. C. Tong Comparison of Triflusal and Aspirin for Prevention of Vascular Events in Patients After Cerebral Infarction: The TACIP Study: A Randomized, Double-Blind, Multicenter Trial * Can Aspirin Ever Be Surpassed for Stroke Prevention? Stroke, April 1, 2003; 34(4): 840 - 848. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Castro-Beiras and G.F. Gensini Introduction Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I1 - I2. [PDF]
|
|
|
|
|
|
J.C. Kaski and E.G. Zouridakis Inflammation, infection and acute coronary plaque events Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I10 - I15. [Abstract] [PDF]
|
|
|
|
|
|
L. Badimon, G. Vilahur, S. Sanchez, and X. Duran Atheromatous plaque formation and thrombogenesis: formation, risk factors and therapeutic approaches Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I16 - I22. [Abstract] [PDF]
|
|
|
|
|
|
J.M. Cruz-Fernandez Antiplatelet drugs in the treatment of acute coronary syndromes: Focus on cyclooxygenase inhibitors Eur. Heart J. Suppl., August 1, 2001; 3(suppl_I): I23 - I30. [Abstract] [PDF]
|
|
|
|
|
|
J. Lopez-Sendon Coronary reperfusion in the clinical setting: antithrombotic support to thrombolysis in the coronary care unit Eur. Heart J. Suppl., June 1, 2001; 3(suppl_C): C55 - C61. [Abstract] [PDF]
|
|
|
|
|
|
A Bayes de Luna May aspirin be replaced in the treatment of myocardial infarction? Eur. Heart J., March 2, 2000; 21(6): 430 - 432. [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||