Clinical Review

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

Journal of Clinical Outcomes Management. 2015 December;22(12)

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A subgroup analysis of ROCKET-AF evaluating rivaroxaban 15 mg daily in patients with a CrCl of 30–49 mL/min did not identify any differences in endpoints with the exception of fatal bleeding, which occurred less often with rivaroxaban (0.28%/yr vs. 0.74%/yr; P = 0.047) [64].

Monitoring of renal function is essential to mitigate the risk of drug accumulation. Clinicians should consider obtaining a baseline renal assessment with annual reassessments in patients with normal (CrCl ≥ 80 mL/min) or mild (CrCl 50–79 mL/min) renal impairment, and 2 to 3 times per year in patients with moderate (CrCl 30–49 mL/min) renal impairment [65]. A summary of renal dose adjustments for DOAC therapy may be found in Table 5 [56–59].

In addition to renal function, hepatic impairment can also affect the metabolism of anticoagulants. Severe hepatic impairment can lead to prolonged PT. Therefore, patients who have liver dysfunction and are treated with anticoagulation have increased risk of hemorrhagic events. Large pivotal trials on the key indications of dabigatran, apixaban, and rivaroxaban excluded patients with significant signs of hepatic impairment. Table 5 provides dosing recommendations for the different DOACs in the setting of hepatic impairment [56–59].

Polypharmacy And The Potential For Adverse Consequences

Polypharmacy is defined as concomitantly using multiple medications. The likelihood of an adverse drug reaction increases exponentially with the number of drugs taken, independent of the class of medication [66]. Older adults use over the counter (46%) and herbal supplements (52%) while taking prescription medications and 50% of them are noted to have a drug interaction with anticoagulants. This leads to approximately 1 out of 25 older adults at risk for significant drug-drug interactions [67]. Some DOACs have recommendations for dosage reductions in the setting of advanced age ( Table 6 ). Therefore, it is reasonable to assume that advanced age and drug interactions may place patients at greater risk of treatment failure. Further investigations are needed to understand polypharmacy and drug-drug interactions in geriatric patients [68]; however, clinicians should be aware of the potential pharmacokinetic interactions with DOACs ( Table 7 ) [56–59].

Clinicians should review the patient’s entire medication profile and discontinue any unnecessary medications that may interact with one another if possible. There are several pharmacodymanic interactions that should also be considered. Concomitant use of antiplatelets and NSAIDs with DOACs may increase bleeding risk. In many cases NSAIDs may be discontinued. Patients on dual antiplatelet therapy and an anticoagulant are at an increased risk of bleeding. Clinicians should question the need for dual antiplatelet therapy with anticoagulation. The WOEST (What Is the Optimal Antiplatelet and Anticoagulant Therapy in Patients with Oral Anticoagulation and Coronary Stenting) trial suggested that triple therapy (eg, oral anticoagulant plus aspirin plus clopidogrel) is associated with greater risks than benefits in individuals with AF and coronary stents [69, 70].

Costs And Cost-Effectiveness of DOACS

With the high burden of AF and the aging population, analysis of cost and value is an important consideration [76]. There are limited publications comparing the cost-effectiveness between the anticoagulation options. However, numerous cost-effectiveness studies have evaluated the individual DOACs [71–79]. Overall, the studies suggest that the DOACs are a cost-effective alternative to warfarin in the general and elderly populations. One analysis reported that dabigatran may not be cost-effective in patients with a low CHADS2 score (≤ 2) [71].