Definition of Polypharmacy in Atrial Fibrillation and Atrial Flutter: A Scoping Review

Polypharmacy lacks a consistent definition in the literature and studies use varying numeric thresholds, ranging from the use of four to as many as 15 medications with the most frequent cutoff being five or more medications. It is highly prevalent and particularly relevant in patients with atrial fibrillation (AF) and atrial flutter (AFL) who have multiple comorbidities and often require multi-agent therapy. As a result, these patients face increased risk of bleeding, falls, drug-drug interactions, adverse drug-related events, and medication non-adherence. This scoping review aims to identify how polypharmacy is defined in AF and AFL, to examine the clinical consequences of these definitions, and summarize considerations to prevent polypharmacy. A comprehensive literature search was completed across five databases to identify articles that address and define polypharmacy in AF and AFL. A protocol was prospectively registered on PROSPERO (CRD420251135482) before data extraction began. Included articles defined polypharmacy in adult patients with a diagnosis of AF or AFL. Of the 109 articles identified, 96% (n = 105) discussed AF only, 4% (n = 4) discussed AF and AFL together without differentiation, and none focused solely on AFL. Most articles (96%, n = 105) used a quantitative definition, while 4% (n = 4) used a qualitative definition. The most common definition of polypharmacy, reported in 51% (n = 56) of articles, was the use of five or more medications. This definition is not clinically meaningful as most patients with AF or AFL are already on five or more medications. There is ongoing debate on the definition of polypharmacy in this population. If a numeric cutoff is utilized, we propose increasing it to 10 or more medications as has been suggested in other cardiovascular conditions such as heart failure. More importantly, regardless of how we define polypharmacy in AF or AFL, it is crucial that providers continually assess each medication to ensure that the benefits outweigh the risks.