Discussion
This retrospective 10-year nationwide cohort study enrolled two national cohorts shows that the arterial thromboembolic events, ischemic stroke and MI, were higher in matched patients with AF cohort than those with VTE cohort. Second, the VTE cohort had higher incidence of ECATE than AF cohort, particularly lower extremity thromboembolism. Third, the AF cohort had higher incidence of CV death, but lower incidence of all-cause mortality compared to the VTE cohort. (Figure 6 and Supplemental table 9) In subgroup analyses comparing the DVT-only, PE-only and AF cohorts, the AF patients had highest incidence of ischemic stroke among the three cohorts and had similar incidence of MI compared to patients with PE-only. Patients with DVT-only had highest incidence of ECATE among the three cohorts, particularly lower extremity thromboembolic event. In terms of mortality, patients with PE-only had highest incidence of CV death and all-cause mortality. (Supplemental table 9)
A national 20-year observational study demonstrated that patients with VTE had a 1.26-1.31fold increased risk of subsequent arterial thromboembolic events, including MI and stroke. 11Schulman et al. also showed that VTE was associated with a 1.28 fold increased risk of MI or stroke over a 10-year follow-up period.24 Epidemiological studies and meta-analysis have also recognized that AF is independently associated with a five-fold increased risk of stroke1, 1.47 fold increased risk of MI 25, and a two-fold increased risk of mortality.26
Although VTE and AF contribute to similar arterial thromboembolic events, we are unaware of any study that has compared the different presentations of arterial thromboembolic events between VTE and AF patients, from the same population cohort. Based on our study, AF contributed to more arterial thromboembolic events while VTE contributed to greater all-cause mortality. In terms of the causes of mortality, more AF patients (66.6%) died from cardiovascular death than VTE patients (56.4%) while more VTE patients (13.7%) died from cancer than AF patients (8.6%) (Supplemental table 5). Our results were generally consistent with other studies in terms of causes of death in VTE and AF patients.27
As mentioned above there are many parallels between the epidemiology of risk factors and associated pathogenesis of thrombosis in AF and VTE.4-6,8,28 Nonetheless, our study showed some differential distributions of baseline characteristics between VTE and AF cohorts. Of note, the prevalence of peripheral artery disease and cancer was higher in VTE cohort than AF cohort. In contrast, the prevalence of ischemic heart disease and heart failure was higher in AF cohort than VTE cohort. Importantly, even after propensity matching, AF cohort had higher risks of arterial thromboembolic event, ischemic stroke and MI compared to the VTE cohort. VTE cohort had higher all-cause mortality while AF cohort had higher CV mortality. Therefore, VTE and AF patients have different risks in presentations related to arterial thromboembolic events; thus, AF and VTE should not be considered as a different side of exactly the same coin.
Long-term anticoagulation therapy to prevent arterial thromboembolism is a well-established strategy in AF population2 and a net clinical benefit more than 5 years with DOACs is still evident.16 On the other hand, long-term anticoagulation was not recommended in VTE population due to uncertain net clinical benefit in the era of vitamin K antagonists (VKA, eg. warfarin).17 However, some studies have shown that extended treatment with DOAC for 6 months to 15 months resulted in less recurrent VTE events than no treatment, and had less bleeding events compared to VKA.29-32 Of note, extended low-dose aspirin in VTE patients for up to 4 years results in a significant reduction in the rate of major vascular events, with improved net clinical benefit in the ASPIRE study.33
Given the different presentations of arterial thromboembolic events between AF and VTE cohorts over a 10-year follow-up period, further studies of extended antithrombotic therapy in preventing arterial thromboembolic events, particularly lower extremity thromboembolic events, in VTE patients are warranted.