Revisión sistemática y metanálisis del tratamiento anticoagulante en la trombosis asociada al cáncer. Implicaciones en estudios de no inferioridad. / Systematic review and meta analysis of anticoagulant treatment in cancer-associated thrombosis. Implications about non-inferiority studies.
Resumen
Resumen.
La trombosis asociada al cáncer (TAC) constituye una complicación frecuente en pacientes con esta enfermedad. Existen tres opciones para la tromboprofilaxis: los anticoagulantes orales directos (ACOD), las heparinas de bajo peso molecular (HBPM) y las anti-vitamina K (warfarina). Se realizó una revisión sistemática para comparar las tres alternativas de tratamiento sobre efectividad bajo criterios de no inferioridad. Adicionalmente se analizaron el empleo de los ACOD y las HBPM contra placebo para evidenciar superioridad. El evento primario fue la trombosis venosa profunda recurrente (TVPr) y para seguridad, la hemorragia mayor. Un total de 9353 pacientes fueron clasificados en cuatro categorías: ACOD vs warfarina (4 estudios), ACOD vs HBPM (3 estudios), HBPM vs warfarina (3 estudios) y ACOD o HBPM vs placebo (4 estudios). Los resultados mostraron una superioridad de los ACOD sobre la warfarina en TVPr, RR(IC95%) igual a 0,70 (0,58-0,87), p<0,001] y una no inferioridad entre los ACOD vs las HBPM y entre las HBPM vs la warfarina, [RR;(IC95%) igual a 0,78; (0,59-1,03), p=0,081 y 0,71 (0,44-1,14), P=0,159 respectivamente]. El análisis de seguridad para hemorragia mayor mostró superioridad de las HBPM sobre los ACOD y la warfarina [RR; (IC95%) igual a 1,69; (1,22-2,33), p<0,002 y 0,72; (0,56-0,93), p<0,001 respectivamente]. Se demostró superioridad de los ACOD y las HBPM versus el placebo, pero el riesgo de hemorragia fue mayor. Se concluye que la ligera ventaja que presentan los ACOD en la reducción de TVPr se ve cuestionada por el mayor riesgo de hemorragia. Se sugiere que la elección del anticoagulante debe ser personalizada, teniendo en consideración el riesgo de hemorragia, el sitio del cáncer, además de los valores y preferencias del paciente.
Abstract.
Cancer-associated thrombosis (CAT) is a frequent complication in cancer patients. There are three options for thromboprophilaxis: new direct oral anticoagulants (NOAC), low molecular weight heparins (LMWH) and antivitamin K (warfarin). The present systematic review was carried out to compare these alternatives on their effectiveness and safety under criteria of non-inferiority. Additionally, the use of NOAC and LMWH against a placebo was analyzed to show superiority. The primary event was deep venous thrombosis recurrence (DVTr) and for security, major bleeding. A total of 9353 patients were classified in four categories: NOAC vs warfarin (4 studies), NOAC vs LMWH (3 studies), LMWH vs. warfarin (3 studies) and NOAC or LMWH vs placebo (4 studies). The results show a superiority of NOAC over warfarin [RR; (95% CI) = 0.70; (0.58-0.87), p <0.001] and a non-inferiority of NOAC vs LMWH and LMWH vs. warfarin (RR; (95%CI) = 0.78;(0.59-1.03), p= 0.081 and 0.71; (0.44-1.14), p= 0.159 respectively]. Safety analysis for major bleeding showed superiority of LMWH over NOAC and warfarin [RR; (95%CI) = 1.69; (1.22-2.33), p <0.002 and 0.72;(0.56-0.93), p <0.001 respectively]. Studies showed superiority of NOAC / LMWH vs placebo, but the risk of bleeding was higher. It is concluded that the slight advantage of NOAC in the prevention and reduction of DVTr is questioned by the increased risk of bleeding. It is suggested that the choice of anticoagulant should be personalized, considering the risk of bleeding from the patient, the cancer site and the patient’s values and preferences.
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