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Objective To evaluate the impact of coadministering statins with direct oral anticoagulants (DOACs) on the risk of major bleeding events in patients with venous thromboembolism (VTE).Design Observational cohort analysis based on a multicentre international registry.Setting Data were extracted from the Registro Informatizado de Enfermedad TromboEmbolica Registry, which involves 205 centres across 27 countries.Participants A total of 73 659 patients diagnosed with VTE were classified based on their anticoagulant therapy (DOACs) versus low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) and concurrent use of statins.Methods Multivariable Cox proportional hazards models adjusted for confounding variables to assess the risk of major bleeding events stratified by the type of anticoagulant use and statin use.Results From October 2013 to February 2023, 73 659 patients were recruited: 2573 were statin users on DOACs, 14 090 were statin users on LMWH or VKA therapy, 10 088 were non-statin users on DOACs and 46 908 were non-statin users on LMWH or VKA therapy. Statin users were 10 years older and more likely to have hypertension, diabetes, renal failure or prior artery disease. During anticoagulation (median, 187 days), 1917 patients (2.6%) suffered major bleeding. Rates of major bleeding per 100 patient-years were 2.33 (95% CI 1.72 to 3.09), 3.75 (95% CI 3.43 to 4.10), 1.39 (95% CI 1.13 to 1.69) and 3.10 (95% CI 2.93 to 3.27), respectively. On multivariable analysis, patients treated with DOACs had a significantly lower risk of major bleeding compared with those on LMWH or VKA therapy (adjusted HR 0.59; 95% CI 0.48 to 0.74). The adjusted HR in statin users versus non-users was 1.03 (95% CI 0.92 to 1.14), while in statin users on DOACs versus the rest of patients, it was 1.18 (95% CI 0.79 to 1.76).Conclusions In patients with VTE receiving statins, long-term anticoagulation with DOACs was associated with a reduced risk of major bleeding, regardless of the statin use. These findings support the safety profile of DOACs over VKAs or LMWH in the management of VTE in patients requiring statins.

Venous thromboembolism (VTE) after hospital discharge poses a serious health risk. Assessments of patient characteristics, prophylaxis, treatment, outcomes, and over time changes lack consistency. Data on 16,901 hospitalized patients in the Registro Informatizado Enfermedad TromboEmbolica registry (2003-2022) were analyzed to evaluate trends in baseline characteristics, prophylaxis, treatments, and 90-day outcomes among medical (6,218) and surgical (10,683) patient cohorts. Multivariable logistic regression was used to assess the risks of the composite of fatal pulmonary embolism (PE) or recurrent VTE and major bleeding. The proportion of patients who presented with PE increased among medical (from 54 to 72%) and surgical patients (from 55 to 58%). Prophylaxis use increased in medical patients (from 53 to 71%), while decreasing in surgical patients (from 67 to 58%). Notably, the 90-day composite of fatal PE or recurrent VTE decreased in medical (from 3.9 to 1.8%) and surgical patients (from 2.9 to 1.2%; p  < 0.001 for both). Conversely, major bleeding increased (3.1 to 4.5%) in medical patients ( p  = 0.008), with no change in surgical patients (from 2.5 to 2.4%). Risk-adjusted analysis showed a yearly decrease in the risk for the composite outcome (subhazard ratio [sHR]: 0.95; 95% confidence interval [CI]: 0.93-0.98) in medical and surgical patients and an increase in the risk for major bleeding in medical patients only (sHR: 1.04; 95% CI: 1.01-1.07). Results were consistent after excluding coronavirus disease 2019 patients. Over 20 years, the composite of fatal PE or recurrent VTE within 90 days had significantly decreased in VTE patients after hospitalization for medical or surgical care. Medical patients, however, exhibited an increase in major bleeding., Competing Interests: B.B. declares receiving honoraria for lectures and advisory board contributions from Sanofi, ROVI Laboratories, Johnson & Johnson, and HORIBA Medical. B.B. is supported by a Career Development Award from the American Heart Association and VIVA Physicians (#938814). B.B. was supported by the Scott Schoen and Nancy Adams IGNITE Award and is supported by the Mary Ann Tynan Research Scientist award from the Mary Horrigan Connors Center for Women's Health and Gender Biology at Brigham and Women's Hospital, and the Heart and Vascular Center Junior Faculty Award from Brigham and Women's Hospital. B.B. reports that he was a consulting expert, on behalf of the plaintiff, for litigation related to two specific brand models of inferior vena cava (IVC) filters. B.B. has not been involved in the litigation in 2022 to 2024 nor has he received any compensation in 2022 to 2024. B.B. reports that he is a member of the Medical Advisory Board for the North American Thrombosis Forum and serves in the Data Safety and Monitory Board of the NAIL-IT trial funded by the National Heart, Lung, and Blood Institute, and Translational Sciences. B.B. is a collaborating consultant with the International Consulting Associates and the U.S. Food and Drug Administration in a study to generate knowledge about utilization, predictors, retrieval, and safety of IVC filters. Other authors disclose no potential conflict of interest., (Thieme. All rights reserved.)

The clinical significance and optimal therapy of patients with subsegmental pulmonary embolism (SSPE) remain controversial. We used the data in the RIETE Registry to compare the baseline characteristics, treatment, and outcomes during anticoagulation and after its discontinuation in patients with asymptomatic vs. symptomatic SSPE. From January 2009 to September 2022, there were 2135 patients with a first episode of SSPE, of whom 160 (7.5%) were asymptomatic. Most patients in both subgroups received anticoagulant therapy (97% vs. 99.4%, respectively). During anticoagulation, 14 patients developed symptomatic pulmonary embolism (PE) recurrences, 28 lower-limb deep vein thrombosis (DVT), 54 bled, and 242 died. The patients with asymptomatic SSPE had similar rates of symptomatic PE recurrences (hazard ratio (HR): 2.46; 95% CI: 0.37-9.74), DVT (HR: 0.53; 95% CI: 0.03-2.80), or major bleeding (HR: 0.85; 95% CI: 0.21-2.42) to those with symptomatic SSPE, but had a higher mortality rate (HR: 1.59; 95% CI: 1.25-2.94). The rate of major bleeding outweighed the rate of PE recurrences (54 major bleeds vs. 14 PE recurrences), and the rate of fatal bleeds outweighed the rate of fatal PE recurrences (12 vs. 6 deaths). After discontinuing anticoagulation, the patients with asymptomatic SSPE had a similar rate of PE recurrences (HR: 1.27; 95% CI: 0.20-4.55) and a non-significantly higher mortality rate (HR: 2.06; 95% CI: 0.92-4.10). The patients with asymptomatic SSPE had similar rates of PE recurrences to those with symptomatic SSPE, during and after discontinuing anticoagulation. The unexpectedly higher rate of major bleeding than recurrences highlights the need for randomized trials to find the best management.