Clinical Review

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


 

References

From the Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ.

Abstract

  • Objective: To provide a clinical summary of the available data evaluating the use of direct oral anticoagulants (DOACs) in geriatric patients with nonvalvular atrial fibrillation.
  • Methods: MEDLINE, Web of Science, and Google Scholar were used to identify pertinent systematic reviews, randomized controlled trials, observational studies, and pharmacokinetic studies evaluating use of DOACs in the geriatric population.
  • Results: A total of 8 systemic reviews, 5 randomized controlled trials, 2 observational trials, and 5 pharmacokinetic studies of relevance were identified for inclusion in this review. The landscape of anticoagulation has dramatically changed over the past 5 years beginning with the development and marketing of an oral direct thrombin inhibitor and followed by 3 oral direct factor Xa inhibitors. Despite significant advances in this oral anticoagulation arena, many questions remain as to the best therapeutic approach in the geriatric population as the literature is lacking. This population has a higher risk of stroke; however, due to the increased risk of bleeding clinicians may often defer anticoagulant therapy due to the fear of hemorrhagic complications. Clinicians must consider the risk-benefit ratio and the associated outcomes in geriatric patients compared to other patient populations.
  • Conclusions: Interpreting the available literature and understanding the benefits and limitations of the DOACs is critical when selecting the most appropriate pharmacologic strategy in geriatric patients.

Anticoagulants are among the top 5 drug classes associated with patient harm in the US [1] and are commonly reported as contributing to hospitalizations [2]. In just one quarter in 2012 alone, warfarin, dabigatran, and rivaroxaban accounted for 1734 of 50,289 adverse events reported to the Food and Drug Administration (FDA), including 233 deaths [3]. Appropriate use of anticoagulant agents and consideration of individual patient risk factors are essential to mitigate the occurrence of adverse consequences, especially in the geriatric population. This population is more likely to have risk factors for adverse drug events, for example, polypharmacy, age-related changes in pharmacokinetics and pharmacodynamics, and diminished organ function (ie, renal and hepatic) [4,5]. Another important consideration is the lack of consensus on the definition of a “geriatric” or “elderly” patient. Although many consider a chronological age of > 65 years as the defining variable for a geriatric individual, this definition does not account for overall health status [6,7]. Clinicians should consider this shortcoming when evaluating the quality of geriatric studies. For example, a study claiming to evaluate the pharmacokinetics of a drug in a geriatric population enrolling healthy subjects aged > 65 years may result in data that do not translate to clinical practice.

Compounding the concern for iatrogenic events is the frequency of anticoagulant use in the geriatric population, as several indications are found more commonly in this age-group. Stroke prevention in nonvalvular atrial fibrillation (AF), the most common arrhythmia in the elderly, is a common indication for long-term anticoagulation [8]. The prevalence of AF increases with age and is usually higher in men than in women [9,10]. AF is generally uncommon before 60 years of age, but the prevalence increases noticeably thereafter, affecting approximately 10% of the overall population by 80 years of age [11]. The median age of patients who have AF is 75 years with approximately 70% of patients between 65 and 85 years of age [8,12]. Currently in the United States, an estimated 2.3 million people are diagnosed with AF [8]. In 2020, the AF population is predicted to increase to 7.5 million individuals with an expected prevalence of 13.5% among individuals ≥ 75 years of age, and 18.2% for those ≥ 85 years of age [13]. These data underscore the importance of considering the influence of age on the balance between efficacy and safety of anticoagulant therapy.

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,

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