External Validity of the ARISTOTLE Trial in Real‐Life Atrial Fibrillation Patients

Abstract

SUMMARYObjective: Our primary objective was to determine the proportion of patients with atrial fibrillation (AF) eligible for enrollment in a randomized controlled trial for a novel oral anticoagulant, the ARISTOTLE trial. A secondary objective was to describe the reasons for trial ineligibility. Methods: We performed a cross-sectional study of an unselected population including 2274 patients in Skellefte a, Sweden with at least one verified episode of AF on or before December 31, 2010. Patients were classified as suitable or unsuitable for anticoagulant treatment according to current guidelines. The enrollment criteria from the ARIS-TOTLE trial were extracted from the original publication and applied to the population. Results: Among all patients with AF, 1579 were classified as suitable for anticoagulant treatment. Of these, only 658 patients (42%) were eligible for participation in the ARIS-TOTLE trial. Among the 921 patients ineligible for participation, 498 did not meet the ECG criteria, 272 had psychosocial problems, and in addition, 78 patients were excluded due to both of these criteria. Conclusion: Our study shows that a majority of the patients in an unselected population with AF suitable for anticoagulant treatment were ineligible for participation in the ARISTOTLE trial. The applicability of the ARISTOTLE trial is therefore unknown for a considerable proportion of patients with AF in real life.

Real‐life Use of Anticoagulants in Venous Thromboembolism With a Focus on Patients With Exclusion Criteria for Direct Oral Anticoagulants

“…Our data, obtained from a large series of consecutive patients with acute VTE, reveal that in real life one in every five such patients had at least one of the exclusion criteria to be recruited in the pivotal randomized trials with DOACs. Not unexpectedly, patients with exclusion criteria had a 4‐fold higher rate of major bleeding (and a 6‐fold higher rate of fatal bleeding) than those without exclusion criteria, as previously reported . In our series, this increased rate of major bleeding was found in patients with metastatic cancer, CrCl levels <30 mL/min, thrombocytopenia, recent major bleeding, and in those with liver failure, but not in pregnant women.…”

“…However, the pivotal trials where their indication was based applied strict exclusion criteria, aimed to exclude patients with a presumed high risk of bleeding. In real life, one in every four patients receiving long‐term anticoagulant therapy would not have been eligible for these trials, and these patients have a higher rate of major bleeding …”

New Biomarkers and Risk Stratification in Atrial Fibrillation

“…Given the caveat that GDF-15 may be nonspecific, this analysis by Wallentin et al 14 was performed in an anticoagulated trial cohort, so the issues of generalizability to the general AF population remain, given that many patients in an unselected population with AF suitable for anticoagulation were ineligible for trial participation. 15 Thus, additional studies are needed in non-anticoagulated AF populations as well as in real-world cohorts that have a broad range of stroke risk and comorbidities. The translational gap for GDF-15 as a prognostic indicator still needs to be bridged before use of GDF-15 becomes common practice to aid risk stratification or make treatment decisions for AF patients.…”

Priorities for Health Economic Methodological Research: Results of an Expert Consultation

“…27,28 Methods of generating, synthesizing and applying real-world evidence from pragmatic trials, registry data and similar sources should be further explored and experiences exchanged. This would allow evaluation of the cost-effectiveness of treatments in practice, as well as generating parameter input for real-world model-based cost-effectiveness studies as opposed to trialbased studies.…”