Search

Background: Polypharmacy, including use of inhibitors of CYP3A4 and P-glycoprotein (P-gp), is common in patients with venous thromboembolism (VTE) and is associated with increased bleeding., Methods: In 8246 patients included in the EINSTEIN-VTE studies for acute VTE, we evaluated the effect of polypharmacy on bleeding and on the relative differences between rivaroxaban and enoxaparin/vitamin K antagonist (VKA). We assessed the incidence of clinically relevant bleeding (major and clinically relevant nonmajor bleeding) by number of comedications (none, 1-3, ≥4) at baseline, and by use of CYP3A4 and/or P-gp inhibitors. Interaction between rivaroxaban versus enoxaparin/VKA and comedication was assessed by Cox regression analysis with p interaction estimates., Results: With increasing number of comedications, the incidence of clinically relevant bleeding rose from 5.7% to 13.3% in rivaroxaban recipients and from 9.1% to 11.1% in enoxaparin/VKA recipients. Whereas rivaroxaban was associated with a reduced bleeding risk compared with enoxaparin/VKA in patients without comedication (hazard ratio [HR] 0.6, 95% confidence interval [CI] 0.4-0.9), the risk was similar in patients with ≥4 comedications (HR 1.2, 95% CI 0.97-1.5, p interaction .002). Use of CYP3A4 and/or P-gp inhibitors was associated with a doubled bleeding risk compared with no use, without a difference between rivaroxaban and enoxaparin/VKA., Conclusion: We conclude that fixed-dose rivaroxaban as compared with enoxaparin followed by dose-adjusted VKA is not associated with an increased bleeding risk in patients with VTE administered polypharmacy in general and CYP3A4 and/or P-gp inhibitors specifically. This implies that the observed increased bleeding risks with polypharmacy and use of CYP3A4 and/or P-gp inhibitors are likely explained by comorbidities and frailty, and not by pharmacokinetic interactions., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Background: Gastrointestinal bleeding frequently complicates anticoagulant therapy causing treatment discontinuation. Data to guide the decision regarding whether and when to resume anticoagulation based on the risks of thromboembolism and recurrent bleeding are scarce., Objectives: We aimed to retrospectively evaluate the incidence of these events after anticoagulant-related gastrointestinal bleeding and assess their relationship with timing of anticoagulation resumption., Methods: Patients hospitalized because of gastrointestinal bleeding during oral anticoagulation for any indication were eligible. All patients were followed up to 2 years after the index bleeding for recurrent major or clinically relevant non-major bleeding, venous or arterial thromboembolism, and mortality., Results: We included 948 patients hospitalized for gastrointestinal bleeding occurring during treatment with vitamin K antagonists (n = 531) or direct oral anticoagulants (n = 417). In time-dependent analysis, anticoagulant treatment was associated with a higher risk of recurrent clinically relevant bleeding (hazard ratio [HR] 1.55; 95% confidence interval [CI] 1.08-2.22), but lower risk of thromboembolism (HR 0.34; 95% CI 0.21-0.55), and death (HR 0.50; 95% CI 0.36-0.68). Previous bleeding, index major bleeding, and lower glomerular filtration rate were associated with a higher risk of recurrent bleeding. The incidence of recurrent bleeding increased after anticoagulation restart independently of timing of resumption., Conclusions: Anticoagulant treatment after gastrointestinal bleeding is associated with a lower risk of thromboembolism and death, but higher risk of recurrent bleeding. The latter seemed to be influenced by patient characteristics and less impacted by time of anticoagulation resumption., (© 2021 International Society on Thrombosis and Haemostasis.)

As a result of the successful completion of their respective phase III studies compared with vitamin K antagonists (VKAs), four direct oral anticoagulants (DOACs) have been approved for the treatment and secondary prevention of venous thromboembolism (VTE). These DOACs-apixaban, dabigatran, edoxaban, and rivaroxaban-have subsequently seen a steady uptake among clinicians since their approval. Despite the suitability of DOACs for a broad range of patients, they are not appropriate in certain situations, whereas in others they require additional considerations such as dose reductions. Subanalyses of phase III trials and studies on specific VTE patient populations have been conducted to evaluate the safety and efficacy of the DOACs in a broad range of settings, such as patients with renal impairment, patients with cancer, patients of childbearing potential, patients with multiple comorbidities and pediatric patients. Furthermore, many recent guidance documents from important hematological societies and other specialists have incorporated several of these developments. These documents also identify the patients for whom DOACs are not suitable and where traditional anticoagulation options such as heparins or VKAs should be considered instead. This review provides an overview of key VTE patient subgroups, the clinical evidence supporting the use of anticoagulation in these patients, and a discussion of the most appropriate approaches to their management, including considerations such as dosing, acute and extended treatment durations, and DOAC selection., Competing Interests: C.E.K. reports personal fees from Bayer Health Care, Boehringer Ingelheim, Bristol Myers Squibb, Daiichi Sankyo, and Pfizer Pharma during the conduct of the study; personal fees from Amgen and Sanofi-Aventis outside the submitted work. S.M. reports grants and personal fees from Aspen, Bayer, BMS/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, GSK, Portola, Sanquin, and Sanofi during the conduct of the study., (Georg Thieme Verlag KG Stuttgart · New York.)