Douxfils J, Buckinx F, Mullier F, Minet V, Rabenda V, Reginster JY, et al.
J Am Heart Assoc. 2014;3(3):e000515
Background:
Signals of an increased risk of myocardial infarction (MI) have been identified with dabigatran etexilate in randomized controlled trials (RCTs).
Methods and results:
We conducted searches of the published literature and a clinical trials registry maintained by the drug manufacturer. Criteria for inclusion in our meta-analysis included all RCTs and the availability of outcome data for MI, other cardiovascular events, major bleeding, and all-cause mortality. Among the 501 unique references identified, 14 RCTs fulfilled the inclusion criteria. Stratification analyses by comparators and doses of dabigatran etexilate were conducted. Peto odds ratio (ORPETO) values using the fixed-effect model (FEM) for MI, other cardiovascular events, major bleeding, and all-cause mortality were 1.34 (95% CI 1.08 to 1.65, P=0.007), 0.93 (95%CI 0.83 to 1.06, P=0.270), 0.88 (95% CI 0.79 to 0.99, P=0.029), and 0.89 (95% CI 0.80 to 1.00, P=0.041). When compared with warfarin, ORPETO values using FEM were 1.41 (95% CI 1.11 to 1.80, P=0.005), 0.94 (95%CI 0.83 to 1.06, P=0.293), 0.85 (95% CI 0.76 to 0.96, P=0.007), and 0.90 (95% CI 0.81 to 1.01, P=0.061), respectively. In RCTs using the 150-mg BID dosage, the ORPETO values using FEM were 1.45 (95% CI 1.11 to 1.91, P=0.007), 0.95 (95% CI 0.82 to 1.09, P=0.423), 0.92 (95% CI 0.81 to 1.05, P=0.228), and 0.88 (95% CI 0.78 to 1.00, P=0.045), respectively. The results of the 110-mg BID dosage were mainly driven by the RE-LY trial.
Conclusions:
This meta-analysis provides evidence that dabigatran etexilate is associated with a significantly increased risk of MI. This increased risk should be considered taking into account the overall benefit in terms of major bleeding and all-cause mortality.
Comentario del Dr. Fernando Arribas
Se trata de un metaanálisis, publicado en 2014, en el que se incluyen 14 ensayos clínicos controlados y aleatorizados en los que se compara el tratamiento anticoagulante con dabigatrán en diferentes contextos y frente a diversos anticoagulantes. El análisis encuentra un mayor riesgo de infarto agudo de miocardio en aquellos pacientes tratados con dabigatrán [OR 1,34; IC 95% (1,08-1,65); p=0,007], si bien no muestra diferencias en la incidencia de otros eventos cardiovasculares. Por otra parte, de marcada relevancia, el metaanálisis demuestra una reducción en la incidencia de sangrado mayor y de muerte por cualquier causa en los pacientes tratados con dabigatrán. Al comparar el efecto de dabigatrán, específicamente frente a warfarina, los resultados son superponibles a los previos.