Abstract 15651: The Burden of Nontreatment or Undertreatment Among Non-valvular Atrial Fibrillation Patients With Elevated Stroke Risk: A Systematic Literature Review of Real-world Evidence

Abstract

Introduction: Global treatment guidelines (e.g., AHA/ACC/HRS, ESC, JCS) recommend treatment with oral anticoagulants (OACs) for patients with non-valvular atrial fibrillation (NVAF) and an elevated stroke risk, defined by CHA 2 DS 2 -VASc score ≥2. However, not all patients with NVAF and an elevated stroke risk receive guideline-recommended therapy. A systematic literature review of observational studies was undertaken based on PRISMA guidelines to identify the body of evidence on untreated and undertreated NVAF among patients with elevated stroke risk, and assess its epidemiological and clinical burden. Methods: An extensive search of MEDLINE, GoogleScholar, the Cochrane Library, relevant conference proceedings, and health technology assessments (HTAs) was conducted for RWE studies. Studies published between 1/2010-4/2020 were included if they evaluated rates of nontreatment or undertreatment in NVAF. Nontreatment was defined as absence of OACs, while undertreatment was defined as treatment with only antiplatelet agents. Studies focusing on valvular AF were excluded. Results: Thirty-nine published studies (13 countries) met inclusion criteria. Rates of nontreatment for patients with elevated stroke risk ranged from 2.0%-51.1% (median: 23.3%), while rates of undertreatment ranged from 10.0%-45.1% (median: 34.6%). Few studies assessed the relationship between nontreatment or undertreatment and clinical outcomes in the evaluated population. Among US outpatients with NVAF and an elevated stroke risk, those undertreated had a higher likelihood of death (HR: 1.22; 95% CI: 1.05-1.41; p=.006) compared to patients treated with OACs. Also, in a separate US study of NVAF patients with varying levels of warfarin exposure, patients with no warfarin exposure had significantly higher rates of ischemic stroke than patients with low adherence (4.41 vs. 1.87 per 100 person-years, p<.001) or high adherence (4.41 vs. 0.72 per 100 person years, p<.001). Conclusion: Rates of nontreatment and undertreatment among NVAF patients with elevated stroke risk remain high and are associated with potentially preventable cardiovascular events and death. Strategies to increase rates of treatment may reduce adverse clinical outcomes.

Temporal trends in anticoagulation use and clinical outcomes among medicare beneficiaries with non-valvular atrial fibrillation

“…Our findings add to the timeline of real-world observations of OAC treatment for NVAF after the introduction of DOACs and are generally consistent in directionality [ 19 – 23 , 25 – 31 ]. In their cross-sectional registry study of > 400,000 patients with AF from 2008–2012, Hsu et al found that ~ 45% were treated with an OAC over the entire study period—among whom 90% were prescribed warfarin, 8% dabigatran (2010 FDA approval), and 2% rivaroxaban (2011 FDA approval) [ 20 ].…”

“…Ko et al found that among Medicare beneficiaries, 67.1% of patients with incident AF in 2020 had not initiated an OAC within 12 months of diagnosis [ 44 ]. While legitimate considerations for contraindications due to comorbidity, polypharmacy, extremely high bleeding risk, or unobserved antiplatelet or aspirin prescription may play a role, there may also be some clinical inertia attributable to inappropriate concerns regarding older age, sex, frailty, or moderate bleeding risk, as well as suboptimal guideline awareness [ 23 , 24 , 45 ]. A study by Navar et al suggests differences at the provider‐ and health-system‐level are more of a driving factor in the underutilization of DOAC treatment than patient level factors among patients with NVAF [ 45 ].…”

“…Nonetheless, underutilization of OAC treatment in clinical practice has been reported from the period before the introduction of DOACs through early post-market surveillance [ 18 – 22 ]. Moreover, this underutilization has been associated with adverse outcomes [ 23 , 24 ]. The timing of these prior studies in relation to DOAC rollouts underscores the importance of understanding the evolving impact of DOACs on real-world NVAF treatment patterns and associated outcomes.…”

The IMPact of untReated nOn-Valvular atrial fibrillation on short-tErm clinical and economic outcomes in the US Medicare population: the IMPROVE-AF model

“…Despite the most recent recommended guidelines from the AHA/ACC/HRS 8 as well as a high proportion of patient eligibility for anticoagulation, 15 a systematic literature review of real-world evidence studies plus a recent Medicare claims analysis suggest that the proportion of NVAF patients treated with OACs remains low, with up to 51% of eligible patients not receiving OAC treatment. 16,17 A prior health economic modeling exercise estimated the financial A c c e p t e d M a n u s c r i p t implications for Medicare of increased thromboprophylaxis among Medicare-eligible patients with moderate-to-high risk of stroke. 18 However, this model was developed before the widespread introduction of DOACs, and therefore could not estimate their clinical and economic impact.…”

“…Literature-derived clinical estimates were obtained from a number of published sources, including a global systematic literature review presented at the American Heart Association Scientific Sessions 2020 in Dallas, Texas. 16 All calculations for this model were developed and executed in Microsoft Excel for Mac version 16.42.…”