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.