Objective:
Post-hoc analysis of three pivotal clinical trials suggests no difference in risk of ischemic stroke or systemic embolism among cancer patients with atrial fibrillation treated with direct oral anticoagulants (DOACs) vs. warfarin. However, these studies were underpowered and also do not reflect the context of real-world use. We compared the effectiveness of DOACs versus warfarin for the risk of stroke or systemic embolism and all-cause death in patients with NVAF.
Methods:
We used Surveillance, Epidemiology, and End Results (SEER)-Medicare data from 2009 to 2016 and included patients aged ≥66 years diagnosed with cancer (breast, bladder, colorectal, esophagus, lung, ovary, kidney, pancreas, prostate, stomach or uterus) and NVAF. We limited the cohort to patients who newly initiated warfarin or DOACs (from 2010 to 2016) with no history of ischemic stroke or systemic embolism. The primary outcome was hospitalization due to ischemic stroke or systemic embolism and the secondary outcome was all-cause death. We used Fine and Gray’s competing risk model, while treating death as a competing risk, to determine the association of oral anticoagulants with the incidence of stroke or systemic embolism. We also adjusted the analysis using inverse probability of treatment weighted (IPTW). Additionally, an IPTW-adjusted Cox proportional hazards regression model was constructed for all-cause death.
Results:
Of 1,028,784 patients with cancer, 158,744 (15.4%) were diagnosed with atrial fibrillation. After applying all inclusion criteria, the final study cohort included 7,334 cancer patients diagnosed with incident NVAF who newly initiated warfarin or DOACs, of which 3,194 (43.6%) used warfarin and 4,140 (56.4%) used DOACs. The unadjusted rate of stroke or systemic embolism was similar among warfarin and DOACs users (1.20 vs. 1.32 cases per 100 person-years, p=0.27). In the IPTW weighted competing risk model, the use of DOACs was not associated with an increased risk of stroke or systemic embolism compared with warfarin users (Hazard Ratio [HR] 1.41, 95% confidence intervals [CI] 0.90-2.20). However, DOACs users had a significantly lower risk of all-cause death compared with warfarin users (HR 0.82, CI 0.74-0.91).
Conclusion:
Among cancer patients diagnosed with NVAF, DOACs had a similar risk for stroke or systemic embolism compared to warfarin, although DOAC use was associated with reduced risk of all-cause mortality.
An intention-to-treat competing-risk model for candidates with hepatocellular cancer awaiting liver transplantation