A randomized clinical trial to evaluate the efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valve and atrial fibrillation or flutter: Rationale and design of the RIVER trial.

The efficacy and safety of rivaroxaban in patients with bioprosthetic mitral valves and atrial fibrillation or flutter remain uncertain. DESIGN: RIVER was an academic-led, multicenter, open-label, randomized, non-inferiority trial with blinded outcome adjudication that enrolled 1005 patients from 49 sites in Brazil. Patients with a bioprosthetic mitral valve and atrial fibrillation or flutter were randomly assigned (1:1) to rivaroxaban 20 mg once daily (15 mg in those with creatinine clearance <50 mL/min) or dose-adjusted warfarin (target international normalized ratio 2.0-30.); the follow-up period was 12 months. The primary outcome was a composite of all-cause mortality, stroke, transient ischemic attack, major bleeding, valve thrombosis, systemic embolism, or hospitalization for heart failure. Secondary outcomes included individual components of the primary composite outcome, bleeding events, and venous thromboembolism. SUMMARY: RIVER represents the largest trial specifically designed to assess the efficacy and safety of a direct oral anticoagulant in patients with bioprosthetic mitral valves and atrial fibrillation or flutter. The results of this trial can inform clinical practice and international guidelines.

Rivaroxaban in Patients with Atrial Fibrillation and a Bioprosthetic Mitral Valve.

BACKGROUND: The effects of rivaroxaban in patients with atrial fibrillation and a bioprosthetic mitral valve remain uncertain. METHODS: In this randomized trial, we compared rivaroxaban (20 mg once daily) with dose-adjusted warfarin (target international normalized ratio, 2.0 to 3.0) in patients with atrial fibrillation and a bioprosthetic mitral valve. The primary outcome was a composite of death, major cardiovascular events (stroke, transient ischemic attack, systemic embolism, valve thrombosis, or hospitalization for heart failure), or major bleeding at 12 months. RESULTS: A total of 1005 patients were enrolled at 49 sites in Brazil. A primary-outcome event occurred at a mean of 347.5 days in the rivaroxaban group and 340.1 days in the warfarin group (difference calculated as restricted mean survival time, 7.4 days; 95% confidence interval [CI], -1.4 to 16.3; P<0.001 for noninferiority). Death from cardiovascular causes or thromboembolic events occurred in 17 patients (3.4%) in the rivaroxaban group and in 26 (5.1%) in the warfarin group (hazard ratio, 0.65; 95% CI, 0.35 to 1.20). The incidence of stroke was 0.6% in the rivaroxaban group and 2.4% in the warfarin group (hazard ratio, 0.25; 95% CI, 0.07 to 0.88). Major bleeding occurred in 7 patients (1.4%) in the rivaroxaban group and in 13 (2.6%) in the warfarin group (hazard ratio, 0.54; 95% CI, 0.21 to 1.35). The frequency of other serious adverse events was similar in the two groups. CONCLUSIONS: In patients with atrial fibrillation and a bioprosthetic mitral valve, rivaroxaban was noninferior to warfarin with respect to the mean time until the primary outcome of death, major cardiovascular events, or major bleeding at 12 months. (Funded by PROADI-SUS and Bayer; RIVER ClinicalTrials.gov number, NCT02303795.).

Terapia anticoagulante no tromboembolismo venoso / Anticoagulant therapy in venous thromboembolism

Introdução: O tromboembolismo venoso (TEV), incluindo a embolia pulmonar (EP) e a trombose venosa profunda (TVP), é a terceira causa de mortalidade em todo o mundo. O diagnóstico ainda é subestimado nas emergências. Os fatores desencadeantes são bem definidos, o que auxilia a estratificação de risco e o diagnóstico de TEV provocada ou não e influenciará muito o tempo de tratamento. O aumento do ventrículo direito e de marcadores biológicos tem desempenhado grande papel no prognóstico. O quadro clínico é bem definido e tem várias ferramentas, tanto para o diagnóstico como para a estratificação de risco, tais como os critérios de Wells e de Genebra, além de outros. Os exames complementares atualmente estão bem definidos, com a angiografia pulmonar sendo o padrão de referência; porém, com a melhora da tecnologia e a alta sensibilidade e especificidade, a angiotomografia computadorizada ocupou um lugar de destaque. Outros exames ainda são importantes em várias situações, como o D-dímero e outros biomarcadores, a radiografia de tórax, a cintilografia de perfusão/ventilação, eletrocardiograma, ecocardiografia e doppler venoso de membros inferiores. Método: Neste artigo, revisamos aspectos básicos de epidemiologia, diagnóstico e estratificação de risco. O foco principal foi o tratamento com a terapia anticoagulante, sobre a qual revisamos os seis estudos clínicos descritos entre 2009 e 2013, que abordam os novos anticoagulantes orais, hoje denominados anticoagulantes orais diretos. Esses estudos têm desenhos diferentes, com três deles começando com anticoagulantes orais desde o início do quadro agudo de TVP e EP (rivaroxabana e edoxabana). Os outros três iniciaram com enoxaparina e varfarina durante os primeiros dias e depois seguiram com a medicação do grupo em avaliação (dabigatrana e apixabana). Resultados: Nos estudos analisados, todos obtiveram uma redução (valor de p de não inferioridade) dos eventos de recorrência de TEV com relação à varfarina. Nos desfechos de segurança, definidos como sangramento fatal, clinicamente relevante e outros, os novos anticoagulantes orais obtiveram uma diminuição significativa. Conclusões: Os anticoagulantes orais diretos tiveram redução da recorrência de eventos tromboembólicos (periférico e pulmonar), com redução significativa dos índices de sangramentos fatais ou não. A segurança coloca-os como opção segura e eficaz para o tratamento desses pacientes com risco baixo e intermediário de TEV

Introduction: Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is the third leading cause of death worldwide. The diagnosis is still underestimated in emergencies. The triggering factors are well defined, which assists in the stratification of risk and in the diagnosis of VTE, whether provoked or not, and will greatly influence the treatment time. Increased right ventricle and biological markers have played a large role in the prognosis. The clinical features are well defined, and there are various tools for diagnosis and for risk stratification, such as the Wells and Geneva criteria, among others. Complementary exams are now well defined, with pulmonary angiography being the gold standard, but with improved technology and high sensitivity and specificity, computerized angiotomography has played a prominent role. Other exams are still important in certain situations, such as D-dimer and other biomarkers, chest radiography, perfusion/ventilation scintigraphy, electrocardiogram, echocardiography, and lower limb venous Doppler. Method: In this article we review basic aspects of epidemiology, diagnosis, and risk stratification. The main focus was treatment with anticoagulant therapy, under which we reviewed the six clinical studies described between 2009 and 2013 that address the new oral anticoagulants, now called direct oral anticoagulants. These studies have different designs; three of them start with oral anticoagulants from the onset of acute DVT and PE (rivaroxaban and edoxaban), and the other three start with enoxaparin and warfarin during the first days and then with the medication of the study group being evaluated (dabigatran and apixaban). Results: In the analyzed studies, all of them obtained a reduction (non-inferiority p-value) of the events of VTE recurrence in relation to warfarin. In the safety outcomes, defined as clinically relevant fatal bleeding and others, the new oral anticoagulants achieved a significant reduction. Conclusions: Direct oral anticoagulants had a reduction in the recurrence of thromboembolic events (peripheral and pulmonary), with a significant reduction in rates of fatal or non-fatal bleeding. Their safety makes them a reliable and effective option for the treatment of these patients, with low and intermediate risk of VTE