Bristol-Myers Squibb Company (BMS) and Pfizer have announced results from an analysis of real-world data pooled from four large US insurance claims databases. Among non-valvular atrial fibrillation (NVAF) patients, Eliquis (apixaban) was associated with a lower risk of stroke/SE and lower rates of major bleeding compared to warfarin for the overall population as well as for each of the selected high-risk patient sub-populations. The analysis will be presented at ESC Congress 2017, organized by the European Society of Cardiology, in Barcelona, Spain.

In this real-world analysis, patients with NVAF receiving either Eliquis or other oral anticoagulants were identified through the US Optum, MarketScan, PharMetrics, and Humana databases. The data was pooled after propensity score matching (PSM) was completed within each database. Select high-risk subgroups were stratified by age, CHA2DS2-VASc or HAS-BLED score, congestive heart failure (CHF), coronary artery disease (CAD), and peripheral artery disease (PAD). The CHA2DS2-VASc score is a method for estimating stroke risk in patients with non-valvular atrial fibrillation, and the HAS-BLED score helps to estimate risk of major bleeding in patients with NVAF. In the subgroup analysis, based upon these variables, Eliquis was associated with lower risk of stroke/SE and lower rates of major bleeding compared to warfarin after adjustment for confounding factors. It is important to note that Eliquis increases the risk of bleeding and can cause serious, potentially fatal, bleeding.

“Stroke events continue to be a major concern for patients with NVAF as well as their healthcare providers, and these findings supplement Eliquis clinical trial data,” said Christoph Koenen, M.D., MBA, VP, Development Lead, Eliquis, Bristol-Myers Squibb. “This real-world data analysis helps provide insight into how Eliquis fares in patient populations and settings that clinicians commonly see in practice.”

This observational cohort analysis adds to the body of evidence for Eliquis, which notably includes the Phase 3 ARISTOTLE (Apixaban for Reduction In STroke and Other ThromboemboLic Events in Atrial Fibrillation) clinical trial in which the reduction in risk for stroke/SE, the primary efficacy endpoint for ARISTOTLE, was generally consistent for Eliquis compared with warfarin across various patient subgroups.i Real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. Observational real-world studies can only evaluate association and not causalityii,iii (please see full methodology and additional limitations, as well as indications and important safety information for Eliquis, later in this press release).

“The global need to address stroke related to NVAF has never been greater, and the Bristol-Myers Squibb-Pfizer Alliance is intentionally focused on helping to reduce the risk of stroke for as many patients as possible among a broad range of patient type scenarios,” said Rory O’Connor, M.D., chief medical officer, Pfizer Internal Medicine. “We believe real-world data analyses via the ACROPOLIS program are helping to advance deeper levels of insight into how different patient demographics, comorbidities and disease severity factor into how Eliquis may impact patient outcomes.”

This observational, retrospective analysis was conducted in patients aged 18 years and older who initiated Eliquis or warfarin from January 1, 2013 to September 30, 2015. In each database, 1:1 PSM was used to balance age, gender, region, baseline comorbidities, and prescription comedications. Baseline characteristics were balanced with a mean age of 71 years, mean CHA2DS2-VASc score of 3.0 and mean HAS-BLED score of 2.6. After PSM within each database, the resulting patient-specific results were pooled. Cox proportional hazards models were used to estimate the hazard ratios of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation for each subgroup. The statistical significance of the interaction between treatment and the specific subgroup(s) was evaluated.

Real-world data have the potential to supplement randomized clinical trial data by providing additional information about how a medicine performs in routine medical practice. Real-world data analyses have several limitations. For example, the source and type of data used may limit the generalizability of the results and of the endpoints. Observational real-world studies can only evaluate association and not causality. Due to these limitations, real-world data analyses cannot be used as stand-alone evidence to validate the efficacy and/or safety of a treatment. It is important to note that, at this time, there are no head-to-head clinical trials comparing direct oral anticoagulants.

In this analysis, given the nature of claims data, diagnoses were identified through ICD-9-CM codes, and drug prescriptions were identified through prescription claims. Missing values, coding errors, and lack of clinical accuracy may have introduced bias into the study. Although some of the datasets contain information from different insurance plans that do not overlap at the plan level, others are employer-based claims datasets which may contain duplicate patient records when pooled together; however, the number of such duplicates is likely to be small – based on a published estimate of 0.5 percentiv – and therefore unlikely to have any important effect on results.