Clinical Review

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


 

References

depicts the hazard ratios for stroke and major hemorrhage reported in geriatric subgroup analyses in the landmark studies [29–31,44–46]. Below we describe geriatric subgroup data for each DOAC. Analyses of geriatric subroups are yet to be published in full for edoxaban.

Dabigatran

In a post-hoc analysis of the RE-LY trial, Eikelboom and colleagues found that patients 75 years of age and older treated with dabigatran 150 mg twice daily had a greater incidence of GI bleeding irrespective of renal function compared with those on warfarin (1.85%/year vs. 1.25%/year; P < 0.001) [29]. A higher risk in major bleeding also was seen in dabigatran patients (5.10% versus 4.37%; P = 0.07). As a result, the 2012 Beer’s Criteria lists dabigatran as a potentially inappropriate medication. An analysis was conducted of 134,414 elderly Medicare patients (defined as age > 65 years) with 37,587 person-years of follow-up who were treated with dabigatran or warfarin [44]. Approximately 60% of patients included in the analysis were over age 75 years. Dabigatran was associated with a significant reduction in ischemic stroke: HR 0.80 (CI 0.67–0.96); intracranial hemorrhage: HR 0.34 (CI 0.26–0.46); and death: HR 0.86 (CI 0.77–0.96) when compared with warfarin. As in the Eikelboom study, major gastrointestinal bleeding was significantly increased with dabigatran (HR, 1.28 [95% CI, 1.14–1.44]).

Rivaroxaban

For rivaroxaban, a subgroup analysis of patients ≥ 75 years in the ROCKET-AF trial reported similar rates of major bleeding (HR, 1.11; 95% CI, 0.92–1.34) with rivaroxaban compared with warfarin [31]. Clinically relevant non-major bleeding was significantly higher for patients aged ≥ 75 years compared with patients aged < 75 years ( P = 0.01).

Apixaban

Halvorsen and colleagues found that age did not influence the benefits of apixaban in terms of efficacy and safety [47]. In the cohort of patients aged 75 years or older, major bleeding was significantly reduced compared to warfarin (HR, 0.64; 95% CI, 0.52–0.79). The safety benefits persisted even in the setting of age greater than 75 years and renal impairment. A significant reduction in major bleeding (HR, 0.35; 95% CI, 0.14–0.86) was seen in elderly patients with a CrCl; ≤ 30 mL/min ( n = 221) treated with apixaban versus warfarin. Similarly, in elderly patients with a CrCl 30 to 50 mL/min ( n = 1898) a significant reduction in major bleeding was reported (HR, 0.53; 95% CI, 0.37–0.76). These data are consistent with a meta-regression analysis that found a linear relationship between the relative risk of major bleeding and the magnitude of renal excretion for the DOACs (r 2=0.66, P = 0.03) [48]. In this analysis, apixaban had the most favorable outcomes in terms of major bleeding compared to the other DOACs and also has the least dependence on renal function for clearance. In a pooled analysis of data from landmark trials, Ng and colleagues found that in elderly patients (defined as age > 75 years) with nonvalvular AF, only apixaban was associated with a significant reduction in both stroke and major hemorrhage (Figure 1) [49,50].

Edoxaban

Kato and colleagues performed a subgroup analysis of patients aged 75 years or older enrolled in the ENGAGE TIMI 48 study [50]. Currently the results are only published in abstract form. Regardless of treatment, the risk of major bleeding and stroke significantly increased with age ( P < 0.001). An absolute risk reduction in major bleeding was reported with both 60 mg and 30 mg of edoxaban versus warfarin (4.0%/year and 2.2%/year versus 4.8%/year, respectively; no P value provided).

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