Thromboembolism, mortality, and bleeding in 2,435,541 atrial fibrillation patients with and without cancer. a nationwide cohort study

Background: The number of patients with atrial fibrillation (AF) and cancer is rapidly increasing in clinical practice. The impact of cancer on clinical outcomes in this patient population is unclear, as is the performance of the HAS-BLED (Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol) and CHA2DS2-VASc (Congestive Heart Failure, Hypertension, Age ≥ 75 years, Diabetes Mellitus, Stroke or Transient Ischemic Attack, Vascular Disease, Age 65 to 74 Years, Sex Category) scores. Methods: This was an observational, retrospective cohort study including 2,435,541 adults hospitalized with AF. The authors investigated the incidence rates (IRs) of all-cause and cardiovascular mortality, ischemic stroke, major bleeding, and intracranial hemorrhage (ICH) according to the presence of cancer and cancer types. Results: Overall, 399,344 (16.4%) had cancer, with the most common cancers being metastatic, prostatic, colorectal, lung, breast, and bladder. During a mean follow-up of 2.0 years, cancer increased all-cause mortality (hazard ratio [HR], 2.00; 95% confidence interval [CI], 1.99-2.01). The IR of ischemic stroke was higher with pancreatic cancer (2.8%/y), uterine cancer (2.6%/y), and breast cancer (2.6%/y), whereas it was lower with liver/lung cancer (1.9%/y) and leukemia/myeloma (2.0%/y), in comparison with noncancer patients (2.4%/y). Cancer increased the risk of major bleeding (HR, 1.27; 95% CI, 1.26-1.28) and ICH (HR, 1.07; 95% CI, 1.05-1.10). Leukemia, liver cancer, myeloma, and metastatic cancers showed the highest IRs for major bleeding/ICH. Major bleeding and ICH rates progressively increased with the HAS-BLED score, which showed generally good predictivity with C indexes > 0.70 for all cancer types. The CHA2DS2-VASc score's predictivity was slightly lower in AF patients with cancer. Conclusions: Cancer increased all-cause mortality, major bleeding, and ICH risk in AF patients. The association between cancer and ischemic stroke differed among cancer types, and in some types, the risk of bleeding seemed to exceed the thromboembolic risk.