Researchers used real-world clinical data to try to emulate a randomized controlled trial testing the efficacy of two blood thinners, apixaban and warfarin, in preventing stroke in patients with nonvalvular atrial fibrillation. The study, led by Emma Maud Powell at the London School of Hygiene and Tropical Medicine in the United Kingdom, and published August 29,He in the open access journal PLOS Medicineprovides a method to explore the effects of treatments in patients who are underrepresented or excluded from clinical trials.
Patients with atrial fibrillation (a potentially dangerous medical condition in which the upper chambers of the heart beat irregularly) are often prescribed blood thinners such as apixaban or warfarin to prevent stroke. However, these treatment recommendations are based on results from randomized controlled trials, and it is not known whether they apply to patient populations that were not included in the trial or are present in very low numbers.
In the new study, researchers used routinely collected health data from patients in the United Kingdom to try to emulate an earlier randomized controlled trial that compared the effectiveness of apixaban and warfarin. They attempted to emulate the earlier trial’s approaches to patient eligibility, selection, and analysis. They found that patients prescribed apixaban had similar outcomes to patients prescribed warfarin, but unlike the earlier trial, they did not find apixaban to be superior. The researchers noted that the differences in outcomes may have been related to higher quality of warfarin monitoring, suboptimal apixaban dosing, and differences in patient ethnicity and use of concomitant medications compared with the clinical trial population.
Overall, the study established that using an existing randomized controlled trial (the reference trial) as a guide for the design of an observational analysis of real-life patient data is an effective and valid way to estimate the treatment effects and risks of anticoagulants given to patients with atrial fibrillation. The methods developed in this study can be used to investigate the effects of these medications in patient groups that are excluded or underrepresented in these clinical trials, such as the elderly, those with multiple conditions, and people at increased risk of bleeding. This method can also help medical researchers understand whether the results of randomized controlled trials are transferable to “real-world” practices, and provides a framework that can be adapted to investigate treatment effects for other conditions.
The authors add: “Our study aimed to emulate a landmark trial of oral anticoagulants in patients with atrial fibrillation using routinely collected healthcare data in the UK. The landmark trial-based design provides a framework for studying treatment effects in patient groups excluded or underrepresented in trials.”