Net clinical benefit of anticoagulation in AF patients declines accordingly with age

The net clinical benefit (NCB) of anticoagulation use in patients with atrial fibrillation (AF) appears to decrease with advancing age, and this decline can be attributed to competing mortality risk, as shown in a study.

Presented at the American Heart Association (AHA) 2019 Scientific Sessions, “the results demonstrate that the competing risk of death is an important consideration when estimating the NCB of anticoagulation therapy. We find failing to account for competing risks likely overestimates the NCB of anticoagulation, an effect that is more pronounced at older ages and with more effective anticoagulants,” the investigators said.

A total of 14,946 elderly AF patients (median age, 81 years; 54 percent female; median CHA2DS2-VASc score, 4) from the ATRIA-CVRN* cohort were included in the analysis, among whom 88 percent had comorbid hypertension, 27 percent had diabetes mellitus and 23 percent had comorbid chronic heart failure.

In a Markov state transition model, the NCB with warfarin dropped below the minimal clinically relevant lifetime benefit (defined as 0.10 quality-adjusted life years [QALYs]) beyond the age of 87 years. Apixaban, on the other hand, conferred minimal lifetime net benefit after age 92 years. [Circ Cardiovasc Qual Outcomes 2019;12:e006212]

Sensitivity analyses showed that over a 3-year window, the removal of competing risks of death led to a more favourable NCB at 90 years with warfarin (median difference, 0.010 QALYs, 95 percent confidence interval [CI], 0.009–0.013) and with apixaban (median difference, 0.025 QALYs, 95 percent CI, 0.024–0.026).

“We [also] found that the declining benefit of anticoagulation with advancing age is only modestly affected when accounting for the age-related increase in ischaemic stroke risk,” the investigators pointed out.

The present study has important implications for the clinical care of older adults with AF, they said. Patients aged ≥75 years with elevated stroke risk and advised to use anticoagulants may not get the optimal benefit from anticoagulation. 

“Further, the results indicate that competing risks (eg, life-limiting conditions such as end-stage kidney disease) are a major determinant of reduced NCB at a population level,” they added.

The investigators recommended translating the results to the care of individual patients. “For example … for half of 92-year olds with AF, apixaban may not confer a net benefit. Clinicians must translate if an individual patient’s comorbidity burden will limit the benefits of anticoagulants. This information can then inform a shared decision-making encounter so that the anticoagulation decision advances individual patients’ health priorities.”

The study has several limitations, including those inherent to the study design and data available. The patient sample, although racially/ethnically diverse, is highly representative of the California adult population and may not be completely generalizable to all populations in the US or internationally. Also, there is uncertainty associated with the use of multiple estimates of probabilities from varied sources.

“Future work should focus on incorporating competing risks into estimates of the net clinical benefit of anticoagulation and anticoagulation clinical decision aids,” they concluded.

*Anticoagulation and Risk Factors in Atrial Fibrillation—Cardiovascular Research Network