Comparative Effectiveness and Safety of Direct-acting Oral Anticoagulants and Warfarin in Patients with Venous Thromboembolism and Active Cancer: An Observational Analysis.

There is limited evidence to support the use of direct-acting oral anticoagulants (DOACs) in patients with venous thromboembolism (VTE) and active cancer. This study aimed to assess the effectiveness of DOACs versus warfarin for the prevention of recurrent VTE and major bleeding events in patients with VTE and active cancer. We identified patients with incident VTE and active cancer who newly initiated treatment with DOACs or warfarin from Truven Health MarketScan Commercial Claims and Medicare supplemental databases. Patients were followed up from treatment initiation (index date) until the occurrence of >7-day gap in treatment, the start of the study comparator, an outcome of interest (recurrent VTE or major bleeding), inpatient death, disenrollment, or end of the study period, whichever occurred first. We controlled for confounders via propensity score matching and estimated the hazard ratios (HRs) using Cox proportional hazards regression models. A total of 9952 patients were included in the matched cohort (4976 DOACs users and 4976 warfarin users). Patient characteristics were well balanced after matching. We observed a lower incidence of recurrent VTE (3 vs 5 per 100 person-years) and major bleeding events (2 vs 3 per 100 person-years) in the DOAC group compared to warfarin group, respectively. In Cox regression models, use of DOACs (vs warfarin) was associated with a lower risk of recurrent VTE (hazard ratio (HR), 0.59; 95% CI, 0.42-0.82) and major bleeding events (HR, 0.64; 95% CI, 0.44-0.94). On the basis of our findings, among patients with VTE and active cancer, DOACs offer superior effectiveness with a lower risk of bleeding when compared with warfarin for the secondary prevention of VTE.

Dawwas GK ，Dietrich E ，Smith SM ，Davis K ，Park H ... -  《-》

Effectiveness and safety of rivaroxaban versus warfarin for treatment and prevention of recurrence of venous thromboembolism.

Coleman CI ，Bunz TJ ，Turpie AGG 《-》

Impact of anticoagulant choice on hospitalized bleeding risk when treating cancer-associated venous thromboembolism.

Essentials Bleeding risk by anticoagulant choice for cancer-associated venous thrombosis (CA-VTE) is unknown. 26 894 people with CA-VTE were followed for bleeding in a claims database in the United States. Hospitalized bleeding risk was similar with direct acting oral anticoagulants vs. warfarin. Relative hospitalized bleeding risk varied by cancer type and anticoagulant choice. SUMMARY: Background Direct acting oral anticoagulants (DOACs) are associated with less bleeding than traditional venous thromboembolism (VTE) treatments in the general population but are little studied in cancer-associated VTE (CA-VTE). Objective To determine whether different anticoagulation strategies for CA-VTE have different hospitalized bleeding rates. Patients/Methods We conducted a retrospective study of patients with CA-VTE, diagnosed between 2011 and 2015, in a large administrative database. Using validated algorithms, we identified 26 894 CA-VTE patients treated with anticoagulants and followed them for hospitalized severe bleeding. Cox models were used to assess bleeding risk, adjusted for age, sex, high dimensional propensity score and frailty. Results Over 27 281 person-years of follow-up (median 0.6 years), 1204 bleeding events occurred, for a bleeding rate of 4.4% per patient-year. Bleeding rates varied by cancer type, with the highest rate for upper gastrointestinal cancers (8.6%) and the lowest for breast cancer (2.9%). In Cox models (hazard ratio [HR]; 95% confidence interval [CI]), compared with warfarin, DOACS and low-molecular-weight heparin (LMWH) had similar hazards of bleeding (HR, 0.88; 95% CI, 0.69-1.11 and 0.98; 0.85-1.13). Compared with LMWH, there was no difference in hazard of bleeding with DOACs (0.86; 0.66-1.12). There was heterogeneity in bleeding risk with DOACs by cancer type, with a higher risk of bleeding in upper gastrointestinal cancers and lower risk of bleeding in prostate cancer and hematologic cancers. Conclusions In this practice-based sample of CA-VTE patients, DOACs were associated with similar bleeding risks to warfarin and LMWH. These findings suggest a complex association of bleeding risk with anticoagulant choice in cancer patients.

Zakai NA ，Walker RF ，MacLehose RF ，Adam TJ ，Alonso A ，Lutsey PL ... -  《-》

Case-fatality of recurrent venous thromboembolism and major bleeding associated with aspirin, warfarin, and direct oral anticoagulants for secondary prevention.

The duration of anticoagulation after venous thromboembolic events (VTE) is based on the balance between the risk of recurrent VTE and bleeding. The purpose of this study was to estimate the frequency and case-fatality rate of major bleeding and recurrent VTE during secondary prevention of VTE. MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched through September 2014. Two reviewers independently screened citations to identify trials that enrolled patients for secondary prevention of VTE with direct oral anticoagulants (DOACs), vitamin K antagonists (VKAs), aspirin or placebo. Two reviewers independently extracted data onto standardized forms. Twelve RCTs that enrolled 10,542 patients were included. The rate of major bleeding was 1.6 per 100 patient-years (95% CI, 1.2-2.1), and 0.58 per 100 patient-years (95% CI, 0.24-1.1) on VKAs and DOACs, respectively, with an incidence rate ratio of 0.35 (95% CI, 0.17-0.68, p=0.0023). The case-fatality rates for DOACs and VKAs were not significantly different at 0% (95% CI, 0.0-15.4) and 6.8% (95% CI, 1.4-18.6), respectively. The rate of recurrent VTE was not different between DOACs and VKA, IRR 0.88 (95% CI, 0.15-4.8, p=0.88). Case-fatality rates for recurrent VTE for DOAC and VKAs were 10.8% (95% CI, 4.4-20.9) and 5.6% (95% CI, 1.2-15.4), respectively. Only DOACs showed a significant reduction in the composite outcome of fatal recurrent VTE and fatal bleeding when compared to placebo, IRR 0.40 (95% CI, 0.14-1.0, p=0.03). Case-fatality rates for major bleeding and recurrent VTE for DOACs appear to be similar to those for VKA and the composite of fatal events is lower for DOACs than placebo. Overall, given the favorable safety profile and comparable efficacy of DOAC therapy, the threshold to continue anticoagulation with DOACs after unprovoked VTE should be low if the baseline risk of anticoagulation-related bleeding is not high.

Wu C ，Alotaibi GS ，Alsaleh K ，Linkins LA ，McMurtry MS ... -  《-》

Clinical Outcomes of Direct Oral Anticoagulants vs Warfarin for Extended Treatment of Venous Thromboembolism.

Fang MC ，Reynolds K ，Fan D ，Prasad PA ，Sung SH ，Portugal C ，Garcia E ，Go AS ... -  《JAMA Network Open》