Current and emerging strategies in the management of venous thromboembolism: benefit–risk assessment of dabigatran

Christina L Fanola Department of Cardiovascular and Vascular Medicine, Boston University School of Medicine, Boston, MA, USA Abstract: Venous thromboembolism (VTE) is a disease state that carries significant morbidity and mortality, and is a known cause of preventable death in hospitalized and orthopedic surgical patients. There are many identifiable risk factors for VTE, yet up to half of VTE incident cases have no identifiable risk factor and carry a high likelihood of recurrence, which may warrant extended therapy. For many years, parenteral unfractionated heparin, low-molecular weight heparin, fondaparinux, and oral vitamin K antagonists (VKAs) have been the standard of care in VTE management. However, limitations in current drug therapy options have led to suboptimal treatment, so there has been a need for rapid-onset, fixed-dosing novel oral anticoagulants in both VTE treatment and prophylaxis. Oral VKAs have historically been challenging to use in clinical practice, with their narrow therapeutic range, unpredictable dose responsiveness, and many drug–drug and drug–food interactions. As such, there has also been a need for novel anticoagulant therapies with fewer limitations, which has recently been met. Dabigatran etexilate is a fixed-dose oral direct thrombin inhibitor available for use in acute and extended treatment of VTE, as well as prophylaxis in high-risk orthopedic surgical patients. In this review, the risks and overall benefits of dabigatran in VTE management are addressed, with special emphasis on clinical trial data and their application to general clinical practice and special patient populations. Current and emerging therapies in the management of VTE and monitoring of dabigatran anticoagulant-effect reversal are also discussed. Keywords: novel oral anticoagulants, dabigatran, venous thromboembolism, deep venous thrombosis, pulmonary embolism, oral anticoagulatio

Pharmacogenetics of novel oral anticoagulants: a review of identified gene variants & future perspectives

Novel oral anticoagulants (NOACs) are becoming a therapy of choice in everyday clinical practice after almost 50 years during which warfarin and related coumarin derivatives were used as the main anticoagulants. Advantages of NOACs over standard anticoagulants include their predictable pharmacodynamics and pharmacokinetics, stable plasma concentrations and less drug–drug and food–drug interactions. However, pharmacogenetics has its place in administration of NOACs, as considerable interindividual variations have been detected. In this review, previous findings in pharmacogenetics of dabigatran, rivaroxaban, apixaban and edoxaban are summarized, along with recommendations for studying genes encoding metabolically important enzymes for four selected NOACs. Future directions include identification of clinically relevant SNPs, and change in optimum dosage for patients who are carriers of significant variants

Bleeding complications in patients with gastrointestinal cancer and atrial fibrillation treated with oral anticoagulants

BACKGROUND: Direct oral anticoagulants (DOACs) may increase the risk of gastrointestinal (GI) bleeding in patients with atrial fibrillation (AF) and GI cancer compared with vitamin K antagonists (VKA). METHODS: We conducted a Danish nationwide cohort study comparing the bleeding risk associated with DOAC versus VKA in patients with AF and GI cancer. We calculated crude bleeding rates per 100 person‐years (PYs) for GI and major bleeding. We then compared rates of bleeding at 1 year after initial oral anticoagulation filled prescription by treatment regimen using inverse probability of treatment weighting and Cox regression. RESULTS: The unweighted study population included 1476 AF patients with GI cancer (41.6% women, median age 78 years) initiating a DOAC and 652 initiating a VKA. One‐year risk of GI bleeding was 5.0% in the DOAC group and 4.7% in the VKA group with a corresponding weighted hazard ratio (HR) of 0.95 (95% confidence interval [CI]: 0.63, 1.45). For patients with active cancer, weighted GI bleeding rates were slightly higher in both the VKA and DOAC group, and the weighted HR was 1.00 (95% CI: 0.53, 1.88). The HR was 1.12 (95% CI: 0.71, 1.76) for all bleedings. Hazard ratios for GI bleeding were 0.61 (95% CI: 0.25, 1.52) for patients with upper GI cancer, and 0.92 (95% CI: 0.58, 1.46) in patients with colorectal cancer. CONCLUSION: Evidence from this nationwide cohort study suggests a comparable 1‐year risk of bleeding associated with DOAC compared with VKA among patients with AF and GI cancer