Direct Oral Anticoagulants in Patients With Inherited Thrombophilia and Venous Thromboembolism: A Prospective Cohort Study

Abstract

Background In this prospective cohort study, we aimed to evaluate the efficacy and safety of direct oral anticoagulants (DOACs) versus heparin/vitamin K antagonists for the treatment of venous thromboembolism (VTE) in patients with inherited thrombophilia. Methods and Results We enrolled consecutive patients with acute VTE and inherited thrombophilia treated with DOACs (cases) or heparin/vitamin K antagonists (controls), matched for age, sex, ethnicity, and thrombophilia type. End points were VTE recurrence and bleeding complications; residual vein thrombosis and post‐thrombotic syndrome; VTE recurrence after anticoagulant discontinuation. Two hundred fifty‐five cases (age 52.4±17.3 years, Female 44.3%, severe thrombophilia 33.1%) and 322 controls (age 49.7±18.1 years, Female 50.3%, severe thrombophilia 35.1%) were included. The cumulative incidence of VTE recurrence during anticoagulation was 1.09% in cases versus 1.83%, adjusted hazard ratio (HR) 0.67 (95% CI, 0.16–2.77). The cumulative incidence of bleeding was 10.2% in cases versus 4.97%, HR 2.24 (95% CI 1.10–4.58). No major bleedings occurred in cases (versus 3 in controls). No significant differences regarding residual vein thrombosis and post‐thrombotic syndrome. After anticoagulant discontinuation, DOACs yielded a significantly lower 2‐year VTE recurrence risk versus traditional anticoagulants (HR, 0.61 [95% CI, 0.47–0.82]). Conclusions DOACs and heparin/vitamin K antagonists showed a similar efficacy in treating VTE in patients with thrombophilia. Although major bleeding episodes were recorded solely with heparin/vitamin K antagonists, we noted an overall increased bleeding rate with DOACs. The use of DOACs was associated with a lower 2‐year risk of VTE recurrence after anticoagulant discontinuation.

Clinical Benefits of Oral Anticoagulant Use in Cancer Patients at Increased Risk for Venous Thromboembolism per Khorana Index

“…Due to heterogeneity between oral anticoagulant users and non-users in real-world data, some of the baseline comorbidities and concomitant medications (antiplatelets, NSAIDs, and corticosteroids) were not fully balanced with PS matching, and had to be additionally adjusted for by the multiple logistic regression analysis in order to minimize potential confounding effects. Although NOACs have been associated with increased risk of gastrointestinal, gynecological and urological bleeding in other studies, 41 , 42 such risk was not detected in the present study, which might have been affected by the aforementioned deferential comedication patterns between groups. Due to the limited number of NOAC-using cancer patients satisfying the inclusion criteria for study entry, we had to collectively categorize all the patients on any of the NOAC agents as the NOAC group, regardless of prophylactic or treatment doses used.…”

Efficacy and safety of direct-acting oral anticoagulants compared to vitamin K antagonists in COVID-19 outpatients with cardiometabolic diseases

“…These trials evidences are supported by data from real world and observational studies, where DOACs have demonstrated significantly lower rates for major bleeding and a positive net clinical benefit compared to VKAs [ 10 – 13 ]. In VTE patients, the use of DOACs has also been associated with a lower risk of VTE recurrence even after anticoagulant discontinuation [ 14 , 15 ].…”

Primary prophylaxis of venous thromboembolic disease with direct oral anticoagulants in patients with severe inherited thrombophilia

“…Recently, data from the first‐ever prospective cohort study focused on DOACs versus heparin and VKA for VTE treatment and secondary prevention in patients with inherited thrombophilia was published by Campello et al 16 In this study including a large cohort of patients with thrombophilia experiencing VTE (n = 597), the DOAC efficacy in preventing VTE recurrence was comparable to that observed with VKA and heparin (cumulative incidence of recurrence during anticoagulation, 1.09% [95% CI, 0.22%‐3.31%] in DOAC‐treated patients versus 1.83% [95% CI, 0.74%–4.3%] in controls). For all recurrent events in the DOAC group (n = 3), precipitating factors could be demonstrated, including insufficient compliance, polycythemia vera, and APS occurrence.…”