Older patients with atrial fibrillation (AF) who are frail, cognitively impaired, and often with multiple comorbidities, are at risk for serious adverse events unless they are treated with effective oral anticoagulation. There are few clinical and observational data that have explored frailty and multiple comorbidities in elderly patients, and this article discusses the implications arising from a post-hoc ancillary analysis of the ARISTOTLE trial (Alexander K, et al. Am Heart J. 2018). The ARISTOTLE analysis found that compared to patients with AF and no multi-morbidities, those with high multi-morbidities (≥ 6 comorbidities) were older and clinically more vulnerable (more likely to have falls, cognitive issues and to be underweight), took twice as many medications, and were three-times at risk of dying. While the number of multimorbidities increased the risk of stroke and major bleeding, this was not the case for the risk of intracranial haemorrhages. Of note, the treatment effects of oral anticoagulants (OACs) were similar regardless of the number of comorbidities.
The ARISTOTLE data showed an estimated 15% increase in the risk of major bleeding with each additional comorbidity, suggesting that there is a linear relationship between bleeding risk and the number of comorbidities, with each comorbidity contributing equally. However, identifying frail patients can use two approaches: a cumulative deficit model or a phenotypic model, with both approaches showing overlap in identifying frailty in patients. The ARISTOTLE analysis used a cumulative deficit approach to characterize frailty by the number of individual comorbidities at baseline; it did not consider the occurrence of comorbidities during the trial, nor the severity of each comorbidity. Nor did it consider phenotypic model aspects such as a patient’s strength, nutrition or functional status. Interestingly, data from a single-centre analysis found that assessing frailty, along with CHA2DS2-VASc and HAS-BLED scores, could predict mortality in older AF patients.
Studies assessing the direct impact of frailty upon OAC outcomes are challenging to perform, and the debate of who should or should not be anticoagulated remains. However, based upon the current evidence, the presence of multi-morbidities or frailty in patients with AF should not deter the prescription of OACs.