Castellucci LA, Cameron C, Le Gal G, Rodger MA, Coyle D, Wells PS, et al.
JAMA. 2014;312(11):1122-1135
Importance:
Many anticoagulant strategies are available for the treatment of acute venous thromboembolism, yet little guidance exists regarding which drug is most effective and safe.
Objective:
To summarize and compare the efficacy and safety outcomes associated with 8 anticoagulation options (unfractionated heparin [UFH], low-molecular-weight heparin [LMWH], or fondaparinux in combination with vitamin K antagonists); LMWH with dabigatran or edoxaban; rivaroxaban; apixaban; and LMWH alone) for treatment of venous thromboembolism.
Data sources:
A systematic literature search was conducted using MEDLINE, EMBASE, and the evidence-based medicine reviews from inception through February 28, 2014.
Study selection:
Eligible studies were randomized trials reporting rates of recurrent venous thromboembolism and major bleeding in patients with acute venous thromboembolism. Of the 1197 studies identified, 45 trials including 44,989 patients were included in the analyses.
Data extraction and synthesis:
Two reviewers independently extracted trial-level data including number of patients, duration of follow-up, and outcomes. The data were pooled using network meta-analysis.
Main outcomes and measures:
The primary clinical and safety outcomes were recurrent venous thromboembolism and major bleeding, respectively.
Results:
Compared with the LMWH-vitamin K antagonist combination, a treatment strategy using the UFH-vitamin K antagonist combination was associated with an increased risk of recurrent venous thromboembolism (hazard ratio [HR], 1.42; 95% credible interval [CrI], 1.15-1.79). The proportion of patients experiencing recurrent venous thromboembolism during 3 months of treatment were 1.84% (95% CrI, 1.33%-2.51%) for the UFH-vitamin K antagonist combination and 1.30% (95% CrI, 1.02%-1.62%) for the LMWH-vitamin K antagonist combination. Rivaroxaban (HR, 0.55; 95% CrI, 0.35-0.89) and apixaban (HR, 0.31; 95% CrI, 0.15-0.62) were associated with a lower risk of bleeding than was the LMWH-vitamin K antagonist combination, with a lower proportion of patients experiencing a major bleeding event during 3 months of anticoagulation: 0.49% (95% CrI, 0.29%-0.85%) for rivaroxaban, 0.28% (95% CrI, 0.14%-0.50%) for apixaban, and 0.89% (95% CrI, 0.66%-1.16%) for the LMWH-vitamin K antagonist combination.
Conclusions and relevance:
Using meta-analytic pooling, there were no statistically significant differences for efficacy and safetyassociated with most treatment strategies used to treat acute venous thromboembolism compared with the LMWH-vitamin K antagonist combination. However, findings suggest that the UFH-vitamin K antagonist combination is associated with the least effective strategy and that rivaroxaban and apixaban may be associated with the lowest risk for bleeding.
RESUMEN
El objetivo de este metaanálisis y revisión sistemática es comparar la eficacia y seguridad de 8 opciones de tratamiento de la enfermedad tromboembólica venosa: HBPM, HNF o fondaparinux seguidas de antivitaminas K, HBPM seguida de dabigatrán o de edoxabán, HBPM solo o rivaroxabán o apixabán en monoterapia.
De 1197 estudios identificados fueron incluidos para el análisis 45, con un total de 44 989 pacientes.
Comparando con HBPM seguida de AVK, la HNF seguida de AVK fue asociada con un aumento del riesgo de recurrencia (HR 1,42; IC 95%,1,15-1,79). El porcentaje de pacientes que tuvieron una recurrencia durante los 3 meses de tratamiento fue del 1,84% (IC 95%, 1,33-2,51) con HNF seguida de AVK y 1,3% (IC 95% 1,02-1,62) con HBPM seguida de AVK.
Rivaroxabán (HR 0,55; IC 95%, 0,35-0,89) y apixabán (HR 0,31; IC 95%, 0,15-0,62) fueron asociados con un riesgo más bajo de hemorragia que HBPM seguida de AVK durante los primeros 3 meses de tratamiento: con rivaroxabán 0,49% (IC 95%, 0,29-0,85), con apixabán 0,28% (IC 95%, 0,14-0,50) y con HBPM seguida de AVK 0,89% (IC 95%, 0,66-1,16).
Comentario del Dr. Fernando Uresandi
En este metaanálisis todas las opciones terapéuticas resultaron igual de eficaces que el tratamiento de referencia, heparinas de bajo peso molecular (HBPM) seguido de antivitamina K (AVK), excepto la HNF seguida de AVK que resultó inferior. Así mismo, las 8 opciones fueron igual de seguras, excepto rivaroxabán y apixaban en monoterapia, que redujeron el riesgo hemorrágico en comparación con el tratamiento de referencia.
Consolida la combinación HBPM seguida de AVK como el tratamiento de referencia, pero introduce la alternativa de rivaroxabán o apixaban en monoterapia, como opciones con un perfil de riesgo hemorrágico mejor.
Si en los futuros estudios en fase IV se confirman los resultados de los ensayos pivotales, estos anticoagulantes de acción directa van a suponer un cambio significativo en la gestión de pacientes con trombosis venosas profundas o tromboembolia pulmonar.
