Revisión sistemática de los ensayos clínicos sobre terapia antitrombótica con inhibidores del factor XI / Systematic review of clinical trials on the antithrombotic therapy with factor XI inhibitors

Antecedentes y objetivo La información proveniente de los ensayos clínicos fase 2 sugiere que los inhibidores del factor XI podrían mostrar un perfil de eficacia/seguridad más favorable que las terapias antitrombóticas actuales. El objetivo de esta revisión sistemática es analizar la evidencia disponible derivada de esos estudios. Métodos Se realizó una búsqueda bibliográfica en las bases de datos PubMed, Cochrane Library, Scopus y EMBASE, y en las plataformas de registro de ensayos clínicos Clinical Trials y Cochrane Central Register of Controlled Trials. Los resultados se publicaron según la declaración PRISMA. Resultados Se identificaron un total de 18 ensayos clínicos concluidos o en curso abordando múltiples escenarios, incluyendo fibrilación auricular, ictus, infarto de miocardio y tromboembolismo venoso. Se analizó la evidencia procedente de 8 estudios con resultados disponibles. En general, los estudios fase 2 con inhibidores del factor XI mostraron un perfil adecuado de eficacia y seguridad. El balance beneficio/riesgo fue más favorable en términos de reducción de tromboembolismo venoso en pacientes sometidos a artroplastia total de rodilla. Para esta indicación, los inhibidores del factor XI mostraron una reducción global del 50% en la tasa de complicaciones trombóticas y del 60% en la tasa de hemorragias comparado con enoxaparina. En los estudios de pacientes con fibrilación auricular, ictus e infarto de miocardio se observaron resultados más modestos. Conclusión Los inhibidores del Factor XI abren nuevas perspectivas en el tratamiento y la profilaxis antitrombótica. Los estudios fase 3 en curso permitirán definir los fármacos e indicaciones más idóneas. (AU)

Background and objective Data from phase 2 clinical trials suggest that factor XI inhibitors may exhibit a more favourable efficacy/safety profile than current antithrombotic therapies. This systematic review aims to analyze the available evidence derived from these studies. Methods A literature search in the PubMed, Cochrane Library, Scopus, EMBASE databases, and clinical trial registration platforms Clinical Trials and Cochrane Central Register of Controlled was conducted. The results were reported in accordance with the PRISMA statement. Results A total of 18 completed or ongoing clinical trials addressing multiple scenarios, including atrial fibrillation, stroke, myocardial infarction, and venous thromboembolism, were identified. Evidence from 8 studies with available results was analyzed. Overall, phase 2 studies with factor XI inhibitors demonstrated an acceptable efficacy and safety profile. The benefit-risk balance, in terms of reducing venous thromboembolism in patients undergoing total knee arthroplasty, was more favourable. For this scenario, factor XI inhibitors showed a 50% reduction in the overall rate of thrombotic complications and a 60% reduction in bleeding compared to enoxaparin. Modest results in studies involving patients with atrial fibrillation, stroke, and myocardial infarction were observed. Conclusions Factor XI inhibitors offer new prospects in antithrombotic treatment and prevention. Ongoing phase 3 studies will help define the most suitable drugs and indications. (AU)

Systematic review of clinical trials on antithrombotic therapy with factor XI inhibitors.

INTRODUCTION AND OBJECTIVE: Data from phase 2 clinical trials suggest that factor XI inhibitors may exhibit a more favorable efficacy/safety profile compared to current antithrombotic therapies. The aim of this systematic review is to analyze the available evidence derived from these studies. METHODS: A literature search in the PubMed, Cochrane Library, Scopus, EMBASE databases, and clinical trial registration platforms Clinical Trials and Cochrane Central Register of Controlled was conducted. In accordance with the PRISMA statement, results were reported. RESULTS: A total of 18 completed or ongoing clinical trials addressing multiple scenarios, including atrial fibrillation, stroke, myocardial infarction, and venous thromboembolism, were identified. Evidence from 8 studies with available results was analyzed. Phase 2 studies with factor XI inhibitors, overall, demonstrated an acceptable efficacy and safety profile. The benefit-risk balance, in terms of reducing venous thromboembolism in patients undergoing total knee arthroplasty, was more favorable. For this scenario, factor XI inhibitors showed a 50% reduction in the overall rate of thrombotic complications and a 60% reduction in the rate of bleeding compared to enoxaparin. Modest results in studies involving patients with atrial fibrillation, stroke, and myocardial infarction were observed. CONCLUSIONS: Factor XI inhibitors offer new prospects in antithrombotic treatment and prophylaxis. Ongoing phase 3 studies will help define the most suitable drugs and indications.

Recurrence risk of idiopathic venous thromboembolism. / Riesgo de recurrencia en el tromboembolismo venoso idiopático.

For patients with idiopathic venous thromboembolism (unprovoked), the risk of recurrence is high. Secondary prophylaxis with anticoagulant therapy reduces the thrombotic risk but at the expense of an increased risk of haemorrhage. A number of factors, such as the male sex and an increase in dimer-D concentrations after completing the anticoagulation therapy, are associated with an increased risk of recurrence. Other factors such as residual venous thrombosis have a more controversial and sometimes contradictory relationship. A number of models have been proposed for predicting thrombotic recurrence risk after anticoagulation therapy in unprovoked TVD. However, these models need external validation to determine their current usefulness in clinical practice. In this article, we analyse the risk factors for thrombotic recurrence and the existing prediction models.

A risk score for prediction of recurrence in patients with unprovoked venous thromboembolism (DAMOVES).

BACKGROUND: In patients with unprovoked venous thromboembolism (VTE), the optimal duration of anticoagulation is anchored on estimating the risk of disease recurrence. We aimed to develop a simple risk assessment model that improves prediction of the recurrence risk. METHODS: In a prospective cohort study, 398 patients with a first unprovoked VTE were followed up for a median of 21.3months after discontinuation of anticoagulation. We excluded patients with a strong thrombophilic defect. Preselected clinical and laboratory variables were analyzed based on the independent confirmation of the impact on the recurrence risk, simplicity of assessment, and reproducibility. Multivariable Cox regression analysis was used to develop a recurrence score that was subsequently internally validated by bootstrap analysis. RESULTS: A total of 65 patients (16.3%) had recurrent VTE. In all patients, VTE recurred spontaneously. Male sex (HR=2.89 [95% CI 1.21-6.90] P=0.016), age (HR=1.0310 per additional decade [95% CI 1.01-1.07] P=0.011), obesity (HR=3.92 [95% CI 1.75-8.75] P=0.0001), varicose veins (HR=4.14 [95% CI 1.81-9.43] P=0.0001), abnormal D-dimer during anticoagulation (HR=13.66 [95% CI 4.74-39.37] P=0.0001), high factor VIII coagulant activity (HR=1.01 [95% CI 1.00-1.02] P=0.028) and heterozygous of factor V Leiden and/or Prothrombin G20210A mutation (HR=13.86 [95% CI 5.87-32.75] P=0.0001) were related to a higher recurrence risk. Using these variables, we developed a nomogram [hereafter referred to as DAMOVES score (D-dimer, Age, Mutation, Obesity, Varicose veins, Eight, Sex)] for prediction of recurrence in an individual patient. CONCLUSIONS: The DAMOVES score can be used to predict recurrence risk in patients with a first unprovoked VTE and may be useful to decide whether anticoagulant therapy should be continued indefinitely or stopped after an initial treatment period of at least 3months.