Comparative Effectiveness and Safety of Direct Oral Anticoagulants Versus Warfarin Among Adults With Cancer and Atrial Fibrillation

Abstract

BACKGROUND: While clinical guidelines recommend direct-acting oral anticoagulants (DOAC) over warfarin to treat isolated nonvalvular atrial fibrillation, guidelines are silent regarding nonvalvular atrial fibrillation treatment among individuals with cancer, reflecting the paucity of evidence in this setting. We quantified relative risk of ischemic stroke or systemic embolism and major bleeding (primary outcomes), and all-cause and cardiovascular death (secondary outcomes) among older individuals with cancer and nonvalvular atrial fibrillation comparing DOACs and warfarin. METHODS: This retrospective cohort study used Surveillance, Epidemiology, and End Results cancer registry and linked US Medicare data from 2010 through 2016, and included individuals diagnosed with cancer and nonvalvular atrial fibrillation who newly initiated DOAC or warfarin. We used inverse probability of treatment weighting to control confounding. We used competing risk regression for primary outcomes and cardiovascular death, and Cox proportional hazard regression for all-cause death. RESULTS: Among 7675 individuals included in the cohort, 4244 (55.3%) received DOACs and 3431 (44.7%) warfarin. In the inverse probability of treatment weighting analysis, there was no statistically significant difference among DOAC and warfarin users in the risk of ischemic stroke or systemic embolism (1.24 versus 1.19 events per 100 person-years, adjusted hazard ratio 1.41 [95% CI, 0.92–2.14]), major bleeding (3.08 versus 4.49 events per 100 person-years, adjusted hazard ratio 0.90 [95% CI, 0.70–1.17]), and cardiovascular death (1.88 versus 3.14 per 100 person-years, adjusted hazard ratio 0.82 [95% CI, 0.59–0.1.13]). DOAC users had significantly lower risk of all-cause death (7.09 versus 13.3 per 100 person-years, adjusted hazard ratio 0.81 [95% CI, 0.69–0.94]) compared to warfarin users. CONCLUSIONS: Older adults with cancer and atrial fibrillation exposed to DOACs had similar risks of stroke and systemic embolism and major bleeding as those exposed to warfarin. Relative to warfarin, DOAC use was associated with a similar risk of cardiovascular death and a lower risk of all-cause death.

Current Data and Future Perspectives on Patients with Atrial Fibrillation and Cancer

“…According to a Surveillance, Epidemiology, and End Results cancer registry database analysis, similar risks of stroke, systemic embolism, and severe bleeding have been observed in older persons with cancer and AF who were exposed to NOACs or warfarin. In comparison to warfarin, NOAC use was linked to a decreased risk of death from all causes and a similar risk of cardiovascular death [61].…”

Nonvitamin K oral anticoagulants with proton pump inhibitor cotherapy ameliorated the risk of upper gastrointestinal bleeding

“…Nonvitamin K oral anticoagulants (NOACs) are innovative agents generated in a cascade by thrombin inhibitors or direct factor Xa inhibitors. Numerous studies have shown that NOACs are effective in both the prevention and treatment of venous thromboembolism 1 – 6 . NOACs are gaining popularity because of their rapid onset and offset of action, predictable pharmacodynamics that reduce the need for routine therapeutic monitoring, and fewer dietary or drug interactions in comparison to warfarin 7 .…”