Prevention of Stroke in Patients With Ischemic Stroke or Transient Ischemic Attack
To the Editor:
In the Guidelines for Prevention of Stroke in Patients with Ischemic Stroke or Transient Ischemic Attack,1 the authors did not include a mention of 3 important clinical trials: the Triflusal versus Aspirin in Cerebral Infarction Prevention (TACIP)2, Triflusal versus Aspirin for Prevention of Infarction: a Randomized Stroke Study (TAPIRSS),3 and the National Study for Prevention of Embolism in Atrial Fibrillation (NASPEAF)4 studies. The TACIP2 and Triflusal versus Aspirin for Prevention of Infarction: a Randomized Stroke Study (TAPIRSS)3 studies, performed in 2107 and 431 patients, respectively, showed no differences between triflusal and aspirin in the prevention of vascular events in patients with stroke or transient ischemic attack, but the hemorrhagic risk was markedly lower with triflusal. The NASPEAF study4 was a randomized, multicenter clinical trial, performed in 1209 patients with atrial fibrillation that were divided into 2 groups based on risk for thromboembolism: the high-risk group included nonvalvular plus prior embolism and patients with mitral stenosis with and without prior embolism. All others were included in the intermediate-risk group. Patients in the intermediate-risk group were randomized to 1 of the 3 arms: acenocoumarol (targeted international normalized ratio [INR]: 2 to 3), triflusal 600 mg daily, or a combination of both (targeted INR: 1.25 to 2). In the high-risk group, subjects were assigned to acenocumarol (targeted INR: 2 to 3) or the combination therapy (targeted INR: 1.4 to 2.4). After a median follow-up of 2.76 years, the primary outcome, a composite of vascular death, transient ischemic attack and nonfatal stroke or systemic embolism, whichever came first, was lower in the combined therapy than in the anticoagulant arm in both the intermediate (hazard ratio: 0.33 [95% CI: 0.12 to 0.91]; P=0.02) and the high-risk group (hazard ratio: 0.51 [0.27 to 0.96]; P=0.03). Primary outcome plus severe bleeding was lower with combined therapy in the intermediate-risk group. In a subsequent subanalysis5 of the NASPEAF study,4 published after December 31, 2004, it was evidenced that combined therapy in mitral stenosis patients, compared with anticoagulant-alone therapy, reduced the risk of vascular events by 58.3%.
The NASPEAF study4 demonstrated for the first time that the addition of an antiplatelet drug (triflusal) to reduced intensity anticoagulation in atrial fibrillation patients significantly decreases subsequent vascular events compared with patients receiving standard anticoagulation, and does so without increasing bleeding risk.
From the available information,2–5 it can be concluded that triflusal has a role in the treatment of patients with ischemic stroke or transient ischemic attack, as well as in patients with atrial fibrillation when combined with reduced intensity anticoagulation.
The secretariat, databank, statistical analysis, and expenses for working meetings of the NASPEAF study were partly supported by Uriach Foundation (Barcelona). J. Uriach y Compañía, S.A. is the manufacturer of triflusal.
Sacco RL, Adams R, Albers G, Alberts MJ, Benavente O, Furie K, Goldstein LB, Gorelick P, Halperin J, Harbaugh R, Johnston SC, Katzan I, Kelly-Hayes M, Kenton EJ, Marks M, Schawamm LH, Tomsick T. Guidelines for prevention of stroke or transient ischemic attack. Stroke. 2006; 37: 577–617.
Matías-Guiu J, Ferro JM, Alvarez-Sabín J, Torres F, Jiménez MD, Lago A, Melo T; for the TACIP Investigators. Comparison of triflusal and aspirin for prevention of vascular events in patients after cerebral infarction. The TACIP Study: a randomized, double-blind, multicenter trial. Stroke. 2003; 34: 840–848.
Culebras A, Rotta-Escalante R, Domínguez R, Abiusi G, Famulari A, Rey R, Bauso-Toselli L, Gori H, Ferrari J, Reich E; and the TAPIRSS Investigators. Triflusal vs aspirin for prevention of cerebral infarction: a randomized stroke study. Neurology. 2004; 62: 1073–1080.
Pérez-Gómez F, Alegría E, Berjón J, Iriarte JA, Zumalde J, Salvador A, Mataix L; for the NASPEAF Investigators. Comparative effects of antiplatelet, anticoagulant, or combined therapy in patients with valvular and nonvalvular atrial fibrillation. J Am Coll Cardiol. 2004; 44: 1557–1566.
Pérez-Gómez F, Salvador A, Zumalde J, Iriarte JA, Berjón J, Alegría E, Almería C, Bover R, Herrera D, Fernández C; for the National Study for Prevention of Embolism in Atrial Fibrillation Investigators. Effect of antithrombotic therapy in patients with mitral stenosis and atrial fibrillation: a sub-analysis of NASPEAF randomized trial. Eur Heart J. 2006; 27: 960–967.