A novel bleeding risk score provides clinically relevant stratification for major bleeding risk in patients with cancer-associated venous thromboembolism (VTE) who received direct oral anticoagulant (DOAC) therapy, according to findings published in JACC: CardioOncology.
“The ONCO-DOAC BLEED score integrates cancer-related characteristics, such as cancer type and disease status (including metastatic and terminal cancers), together with patient comorbidities and concomitant medications,” the study authors wrote, noting this approach is intended to balance simplicity with clinical relevance. “Identifying high-risk patients may prompt closer clinical follow-up, careful review of concomitant medications (particularly the use of NSAIDs), and monitoring of changes in patient condition, thereby supporting uninterrupted cancer treatment and optimal VTE management.”
Study Methods
The researchers initiated a multicenter, retrospective cohort study. They gathered data from 1,166 patients with cancer-associated VTE who were treated with DOAC therapy in the COMMAND VTE Registry-2 in Japan. Patients were enrolled between January 2015 and August 2020.
“One of the most compelling aspects of the ONCO-DOAC BLEED score is its deliberate clinical pragmatism. The model incorporates both patient-related and cancer-specific variables that are readily available in routine care and can be implemented without complex calculations or additional tools,” noted Larissa Araújo de Lucena, MD, of Federal University of Rio Grande do Norte, Natal, Rio Grande do Norte, Brazil, and her co-authors in an accompanying editorial.
The risk prediction score was validated externally on an independent cohort from ONCO deep vein thrombosis and ONCO pulmonary embolism studies.
Key Findings
Within 163 days of follow-up, 127 patients (10.9%) experienced a major bleeding event.
Variables that were independently associated with major bleeding included a history of major bleeding, chronic kidney disease, nonsteroidal anti-inflammatory drug use, distant metastatic cancer, terminal cancer, upper gastrointestinal cancer, pancreatic cancer, and uterine cancer on multivariable analysis.
The ONCO-DOAC BLEED score demonstrated moderate discrimination for major bleeding. Compared with other risk scores, in the derivation cohort, the score had a Harrell's concordance index of 0.68 and Uno's concordance index of 0.67, and in the validation cohort, the score had a Harrell's concordance index of 0.62 and Uno's concordance index of 0.63. ONCO-DOAC BLEED demonstrated higher discrimination in the derivation cohort and comparable performance in the validation cohort vs the VTE-BLEED, RIETE, CAT-BLEED, and Perform scores.
“This new tool arrives at an important moment. A recent systematic review and meta-analysis of three randomized trials (n = 2,361) found that reduced-dose DOACs (apixaban at 2.5 mg twice daily or rivaroxaban at 10 mg daily) for extended treatment significantly lowered bleeding risk compared with full-dose regimens, without increasing recurrent VTE. The ONCO-DOAC BLEED score complements this evidence by helping clinicians identify patients who may safely benefit from de-escalation strategies,” de Lucena et al commented.
“However, the discriminative performance of the ONCO-DOAC BLEED score should be interpreted within the context of existing prediction models. The reported C-indexes of 0.68 in the derivation cohort and 0.62 in the validation cohort indicate modest discrimination, consistent with prior bleeding prediction models and reflective of the intrinsic complexity of hemorrhagic risk in active cancer. Accordingly, this risk-stratification tool is best viewed as a risk-stratification instrument rather than a precise individual predictive model.”
“There are important clinical implications. The ONCO-DOAC BLEED score provides a practical framework for personalized anticoagulation decisions. High-risk patients (score ≥2) may benefit from closer monitoring, avoidance of nonsteroidal anti-inflammatory drugs, dose adjustment, or earlier consideration of reduced-dose DOAC therapy. Conversely, identification of lower-risk individuals may support greater confidence in maintaining extended anticoagulation during ongoing cancer treatment,” de Lucena et al added.
Naohiko Nakanishi, MD, PhD, of the Department of Cardiovascular Medicine, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan is the corresponding author of the study.
DISCLOSURES: Part of the support for the COMMAND VTE Registry-2 was provided by Japan Society for the Promotion of Science KAKENHI. For full disclosures of the study authors, visit jacc.org.
