Incidence, characteristics, and prognostic impact of cancers in patients with atrial fibrillation: a report from the GLORIA-AF registry

Abstract Background Cancers and atrial fibrillation (AF) are all aging-related diseases. Coexistence of the two conditions makes management complex due to increased risk of both thromboembolism and bleeding. Purpose The aim of the present study was to analyze the incidence and prognostic impact of cancers in patients with AF in the GLORIA-AF registry. Methods GLORIA-AF registry is a prospective multi-centered international multi-centered AF cohort studies. We characterized these patients according to the presence or absence of a cancer diagnosis when enrolled. The primary endpoints were all-cause mortality, cardiovascular mortality, and major bleeding; the secondary endpoints were major adverse cardiovascular events (MACEs) including all-cause mortality, stroke, and major bleeding. Results The prevalence of cancers was 9.7%. The mean CHA2DS2-VASc and HAS-BLED scores in cancer patients were higher than in non-cancer patients (mean CHA2DS2-VASc 3.5 vs. 3.2, P<0.001; mean HAS-BLED score 1.6 vs. 1.3, P<0.001). Patients with cancers had higher oral anticoagulant use than non-cancer patients (84.4% vs. 81.0%, P<0.001) and were more likely to receive NOACs (58.4% vs. 54.0%, P<0.001). During a mean follow up period of 3 years, AF patients with cancers had significantly higher all-cause mortality (15.0% vs. 8.3%, P<0.001), major bleeding rate (5.3% vs. 3.1%, P<0.001), the composite of all-cause mortality, stroke, and major bleeding (20.0% vs. 12.0%, P<0.001), and composite of all-cause mortality, thromboembolism, and major bleeding than non-cancer patients (21.0% vs. 12.0%, P<0.001), but nonsignificant differences in cardiovascular mortality (3.6% vs. 3.1%, P=0.2), any stroke, transient ischemic attack, or non-central nervous system embolism (3.2% vs. 2.7%, P=0.1), and OAC discontinuation (29.0% vs. 28%, P=0.2). Among the cancers, hematological cancer was associated the highest risk of all-cause mortality (HR=3.7, 95%CI 2.69-5.0, P<0.001) while respiratory cancer was associated the highest risk of major bleeding (HR=2.62, 95%CI 1.24-5.5, P=0.011). After multivariable adjustment, cancer was independently associated with increased risk of all-cause mortality (HR=1.30, 95%CI 1.05-1.62, P=0.018), composite of all-cause mortality, stroke, and major bleeding (HR=1.32, 95%CI 1.04-1.68, P=0.022), and composite of all-cause mortality, thromboembolism, and major bleeding (HR=1.29, 95%CI 1.04-1.60, P=0.022), but the risk of major bleeding was nonsignificantly different (HR=1.16, 95%CI 0.71-1.87, P=0.6). Conclusions Cancer is a common comorbidity in patients with AF and is independently associated with increased risk of poor outcomes including all-cause mortality and MACEs. However, cancer did not increase the risk of cardiovascular mortality, major bleeding, and discontinuation of OAC. Cancer in patients with AF should receive appropriate treatments for the cancer itself and appropriate OAC, although strategies may vary between different cancers.Distribution of caners in GLORIA-AFKaplan-Meier curves for the outcomes