Selecting a Direct Oral Anticoagulant for the Geriatric Patient with Nonvalvular Atrial Fibrillation

Direct oral anticoagulants (DOACs) represent the first alternatives to warfarin in over 6 decades. Currently available products in US include apixaban, dabigatran, edoxaban, and rivaroxaban. DOACs possess many of the characteristics of an ideal anticoagulant, including predictable pharmacokinetics, a wider therapeutic window compared to warfarin, minimal drug interactions, a fixed dose, and no need for routine evaluation of coagulation parameters. The safety and efficacy of the DOACs for stroke prevention in nonvalvular AF have been substantiated in several landmark clinical trials [14–16]. Yet there are several important questions that need to be addressed, such as management of excessive anticoagulation, clinical outcome data with renally adjusted doses (an exclusion criterion in many landmark studies was a creatinine clearance of < 25–30 mL/min), whether monitoring of coagulation parameters could enhance efficacy and safety, and optimal dosing strategies in geriatric patients. This review provides clinicians a summary of data from landmark studies, post-marketing surveillance, and pharmacokinetic evaluations to support DOAC selection in the geriatric population.

Evaluating Bleeding Risk

These tools have been extensively evaluated with warfarin therapy, but their performance in predicting DOAC-related bleeding has not been definitively established. Nonetheless, until tools evaluated specifically for DOACs are developed, it is reasonable to use these for risk-prediction in combination with clinical judgment. As an example, the European Society of Cardiology guideline on the use of non–vitamin K antagonist (VKA) anticoagulants in patients with nonvalvular AF suggests that the HAS-BLED score may be used to identify risk factors for bleeding and correct those that are modifiable [20]. The HAS-BLED score is validated for VKA and non-VKA anticoagulants (early-generation oral direct thrombin inhibitor ximelgatran) [21] and is the only bleeding risk score predictive for intracranial hemorrhage [19]. In a 2013 “real world” comparison, HAS-BLED was easier to use and had better predictive accuracy that ATRIA [22].

One of the major challenges in geriatric patients is that those at highest risk for bleeding are those who would have the greatest benefit from anticoagulation [23]. The prediction scores can help clinicians balance the risk-benefit ratio for anticoagulation on a case by case basis. Although the scoring systems take into consideration several factors, including medical conditions that have been shown to significantly increase bleeding risk, including hypertension, cerebrovascular disease, ischemic stroke, serious heart disease, diabetes, renal insufficiency, alcoholism and liver disease, not all are included in every scoring scheme [23]. These conditions are more common among elderly patients, and this should be taken into account when estimating the risk-benefit ratio of oral anticoagulation [15]. Patients’ preferences should also be taken into account. It is essential for clinicians to clearly discuss treatment options with patients as data suggest that clinician and patient perceptions of anticoagulation are often mismatched [24–26].

Performance of TSOACS in Landmark Studies