Thromboembolic Risk, Bleeding Outcomes and Effect of Different Antithrombotic Strategies in Very Elderly Patients With Atrial Fibrillation: A Sub-Analysis From the PREFER in AF (PRE vention o F Thromboembolic Events- E uropean R egistry in A trial F ibrillation)

Abstract

Background: Increasing age predisposes to both thromboembolic and bleeding events in patients with atrial fibrillation; therefore, balancing risks and benefits of antithrombotic strategies in older populations is crucial. We investigated 1-year outcome with different antithrombotic approaches in very elderly atrial fibrillation patients (age ≥85 years) compared with younger patients.

Methods and results: We accessed individual patients' data from the prospective PREFER in AF (PREvention oF thromboembolic events-European Registry in Atrial Fibrillation), compared outcomes with and without oral anticoagulation (OAC), and estimated weighed net clinical benefit in different age groups. A total of 6412 patients, 505 of whom were aged ≥85 years, were analyzed. In patients aged <85 years, the incidence of thromboembolic events was 2.8%/year without OAC versus 2.3%/year with OAC (0.5% absolute reduction); in patients aged ≥85 years, it was 6.3%/year versus 4.3%/year (2% absolute reduction). In very elderly patients, the risk of major bleeding was higher than in younger patients, but similar in patients on OAC and in those on antiplatelet therapy or without antithrombotic treatment (4.0%/year versus 4.2%/year; P=0.77). OAC was overall associated with weighted net clinical benefit, assigning weights to nonfatal events according to their prognostic implication for subsequent death (-2.19%; CI, -4.23%, -0.15%; P=0.036). We found a significant gradient of this benefit as a function of age, with the oldest patients deriving the highest benefit.

Conclusions: Because the risk of stroke increases with age more than the risk of bleeding, the absolute benefit of OAC is highest in very elderly patients, where it, by far, outweighs the risk of bleeding, with the greatest net clinical benefit in such patients.

Keywords: anticoagulation; atrial fibrillation; major bleeding; thromboembolic events; very elderly.

Figure 1

Incidence of thromboembolic events (stroke/TIA/systemic embolism) at 1 year in patients aged <85 and ≥85 years. Rates of thromboembolic events according to 3 age strata (<75, 75–84, and ≥85 years) are also depicted. TIA indicates transient ischemic attack.

Figure 2

Incidence of major bleeding at 1 year in patients aged <85 and ≥85 years. Rates of major bleeding according to 3 age strata (<75, 75–84, and ≥85 years) are also depicted.

Figure 3

A, Incidence of thromboembolic events (stroke/TIA/SEE) in patients aged <85 and ≥85 years receiving OAC or no OAC (antiplatelet therapy only or no antithrombotic drug). B, Risk of thromboembolic events by 5‐year intervals of age increase in patients receiving OAC vs no OAC. antiPLT indicates antiplatelet; OAC, oral anticoagulant therapy; SEE, systemic embolic event; TIA, transient ischemic attack; TRT, .

Figure 4

A, Incidence of major bleeding in patients aged <85 and ≥85 years receiving OAC or no OAC (antiplatelet therapy only or no antithrombotic drug). B, Risk of thromboembolic events by 5‐year intervals of age increase in patients receiving OAC vs no OAC. antiPLT indicates antiplatelet therapy; OAC, oral anticoagulant therapy; TRT, .

Figure 5

Net clinical benefit, adjusted for the mortality risk, of OAC vs no OAC (antiplatelet therapy only or no antithrombotic drug) according to different age strata, including ischemic stroke, systemic embolism, myocardial infarction, hemorrhagic stroke, and major bleeding as outcome measures. OAC indicates oral anticoagulant therapy.