Reference

Patti G, Lucerna M, Pecen L, et al. 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 (PREvention oF Thromboembolic Events-European Registry in Atrial Fibrillation). J Am Heart Assoc. 2017;6(7):e005657. Published 2017 Jul 23. doi:10.1161/JAHA.117.005657

At a glance

The study supports the extensive use, as indicated by current guidelines, of anticoagulant therapy even in very elderly patients with atrial fibrillation. Because the risk of stroke increases significantly with age, the absolute benefit of oral anticoagulant treatment is greater in older populations, significantly outweighing the risk of bleeding, resulting in a more favorable net clinical benefit the older age.

What is already known

The progressive increase in the general population of the proportion of elderly patients is known, with, in particular, an expected increase of about 3 times over the next 15 years of individuals ≥85 years of age. The prevalence of atrial fibrillation increases with age, with percentages just under 15% in individuals >75 years of age. Consequently, approaches to prevent cardio-embolic complications (mainly stroke) related to atrial fibrillation in older individuals have a significant impact in terms of cardiovascular morbidity and mortality, as well as on health care economics.

Old age remains one of the main reasons why physicians in the real world refrain from prescribing oral anticoagulant treatment in patients with atrial fibrillation: indeed, concern about bleeding complications often leads to under-use of chronic anticoagulant therapy in older patients with atrial fibrillation.

As a result, in advanced ages there is extensive and inappropriate use of aspirin to prevent thromboembolic events related to atrial fibrillation, although robust data have clearly shown that this drug is significantly less effective than oral anticoagulation in such prevention. In patients with atrial fibrillation, since increased age is associated with an increase in both thromboembolic ischemic risk and haemorrhagic risk, an assessment of the risk/benefit ratio with various antithrombotic therapies in older individuals becomes crucial.

Design and Method

The study evaluated clinical outcomes with oral anticoagulant treatment (warfarin or direct oral anticoagulants) compared to no antithrombotic therapy or aspirin therapy in very elderly (age ≥85 years) and extremely elderly (age ≥90 years) patients in a population of 6,412 patients with atrial fibrillation included in the prospective, multicenter, European “PREFER in AF” registry.

Main Findings

The study showed that, in subjects aged ≥85 years, the use of anticoagulant therapy is associated with a 36% reduction in the risk of thromboembolic events (stroke, TIA or systemic embolism). Because of the higher basal thromboembolic risk in patients ≥85 years of age, in this group the above mentioned relative reduction results in a more pronounced absolute ischemia protection than in patients younger. In particular, it was sufficient to treat 50 patients ≥85 years of age for one year with anticoagulant therapy to save a thromboembolic event. The reduction was similar (43%) in the subgroup of extremely elderly patients ≥90 years of age.

Moreover, in patients ≥85 years of age, the incidence of haemorrhagic complications related to anticoagulant treatment is not higher than with aspirin therapy; in particular, there is an absolute excess of 0.8% thromboembolic risk in the absence of anticoagulant treatment, compared to the haemorrhagic risk of the same therapy.

Finally, the study evaluated the net clinical benefit, defined as the cumulative risk of increased thromboembolic and haemorrhagic events, adjusted for the expected mortality of such events; with increasing age there was a gradient in the net clinical benefit in favour of oral anticoagulant therapy compared to no antithrombotic treatment or aspirin treatment, with older patients obtaining the maximum benefit.

Limitation

Being an observational study, the limits are, of course, a possible selection bias and the risk of “residual confounding”. Finally, very frail elderly patients with major functional disabilities had been excluded.

What’s new

The main concern in patients with atrial fibrillation and advanced age must be the thromboembolic risk if anticoagulant treatment is not prescribed, rather than the haemorrhagic risk of such treatment. Data on the efficacy and increased safety of direct oral anticoagulants, as well as logical considerations related to the practical advantages of therapeutic management, make these drugs the anticoagulants of choice even in patients with atrial fibrillation and very old age.

By Giuseppe Patti

 


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