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

BackgroundIncreasing 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 ResultsWe 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.ConclusionsBecause 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.

Risk of hospitalised bleeding in comparisons of oral anticoagulant options for the primary treatment of venous thromboembolism

“…However, both rivaroxaban and apixaban appeared to perform better among younger than older VTE patients, relative to warfarin. This observation is not entirely surprising; bleeding profile is known to vary by age, with risk and antithrombotic drug‐related bleeding increasing with advancing age (Patti et al , ).…”

Efficacy and safety of oral anticoagulant therapy in frail patients with atrial fibrillation

“…These findings were confirmed also in the subgroup of extremely frail patients aged ≥90 years. As a result, a gradient in the net clinical benefit of OACs according to age strata was observed, with the oldest patients getting the greatest advantage [4]. Despite the abovementioned evidence strongly supporting the favourable benefit/risk ratio of OACs in frail patients, VKA therapy is underutilised in this setting, given the phisycians' perception that such treatment is not safe [6].…”

“…A sub-analysis from the ENGAGE AF-TIMI 48 trial have demonstrated a 2-fold and 3-fold elevation in the occurrence of thromboembolic and major bleeding complications, respectively, in AF patients aged ≥75 years versus those with age <65 years [3]. Data from the prospective, real-world PREFER in AF Registry recently showed that, regardless of the antithrombotic therapies, among very elderly (age ≥85 years) patients with AF, the incidence of stroke or systemic embolism was higher compared to any strata of younger age and here by far outweighed the risk of major bleeding (4.8 versus 4 per 100 patients/year); importantly, the propensity to bleeding was not increased in patients aged ≥85 years compared to those with age 75-84 years [4]. This clearly supports the use of OACs even in very elderly patients with AF for preventing arrhythmia-related thromboembolic events.…”

Prevalence of atrial fibrillation and associated anticoagulant therapy in the nonagenarian population of the Community of Madrid, Spain

“…All this despite the fact that anticoagulant treatment has been shown to be much more useful than antiplatelet treatment in reducing stroke risk in patients with AF, particularly in older adults. 24 In addition, antiplatelet therapy is currently not indicated as antithrombotic treatment in AF, although the European Guidelines for the management of AF fibrillation at that time recommended considering antiplatelet therapy if the patient refused anticoagulant treatment. 25 The benefit of VKA treatment in patients with AF is well known, despite the risk of hemorrhage.…”

“…In the Berlin Atrial Fibrillation registry, just 26.5% of patients aged >89 years were receiving anticoagulant treatment; however, one in five was receiving a DOAC, 8 whereas in the PREvention oF Thromboembolic events-European Registry in Atrial Fibrillation (PREFER) registry for AF, 77.8% of those aged >85 years were receiving anticoagulant treatment and 8% of them received a DOAC. 24 In patients with non-valvular AF aged >75 years, treatment with a DOAC is more effective in reducing the risk of stroke, cerebral hemorrhage and mortality than treatment with VKA, without increasing the risk of hemorrhage, although it is unknown whether this is also true in nonagenarians. 7 The low use of DOAC in the present population could be influenced in part by the limitations imposed by the Community of Madrid, which restricted its funding to patients treated with VKA with poor control of international normalized ratio or an inability to monitor it.…”