Are direct oral anticoagulants noninferior to low-molecular-weight heparin for preventing recurrent venous thromboembolism in adults with cancer?
This study found DOACs to be noninferior to LMWH for preventing recurrent VTE over a 6-month follow-up in adults with cancer. Severe adverse events, including major bleeding, occurred similarly in both groups. Outcomes remained similar regardless of specific cancer thrombogenic risk. Patients given DOACs were significantly more likely to still be taking their assigned anticoagulant at 6 months, suggesting a superior outcome with DOACs with longer follow-up.
Plan de l'etude:
Randomized controlled trial (single-blinded)
Long-term anticoagulation is recommended to treat and prevent recurrence of venous thromboembolism (VTE) in patients with cancer. Previous guidelines recommend the use of low-molecular-weight heparin (LMWH), not having sufficient evidence for noninferiority/superiority of direct oral anticoagulants (DOACs). These investigators identified adults, 18 years or older, with solid tumors, lymphoma, chronic lymphocytic leukemia, or multiple myeloma with either advanced disease or a diagnosis within the past 12 months. Eligible patients (N = 671) with symptomatic or asymptomatic VTE detected via imaging within 30 days of enrollment randomly received (concealed allocation assignment) a DOAC or LMWH. Physicians and patients selected any DOAC or any LMWH (or fondaparinux) based on availability, insurance coverage, formulary preference, or drug-drug interactions, and physicians selected the drug doses. Individuals who assessed outcomes remained masked to treatment group assignment. Complete follow-up occurred for all patients at 6 months.
Using both intention-to-treat and per-protocol analysis, recurrent VTE occurred in 6.1% of patients treated with a DOAC and 8.8% of those treated with LMWH, meeting criteria for noninferiority. Of 6 prespecified secondary outcomes, including bleeding events, death, and quality of life, none were significantly different between groups. Major bleeding occurred in 5.2% of patients in the DOAC group and 5.6% in the LMWH group. At 6 months, participants in the DOAC group were significantly more likely to still be taking their assigned anticoagulant (70.9% vs 59.4%; difference 11.5%; 95% CI 4.1% - 18.8%). No significant differences occurred in the incidence of recurrent VTE in the subgroup of patients with highly thrombogenic tumors, indwelling central venous catheter, age at least 65 years, and baseline platelet count.
David C. Slawson, MD
Professor and Vice Chair of Family Medicine for Education and Scholarship
Professor of Family Medicine, UNC Chapel Hill