Representativeness of the dabigatran, apixaban and rivaroxaban clinical trial populations to real-world atrial fibrillation patients in the United Kingdom: a cross-sectional analysis using the General Practice Research Database

BMJ Open. 2012 Dec 14;2(6):e001768. doi: 10.1136/bmjopen-2012-001768. Print 2012.


Objective: Three oral anticoagulants have reported study results for stroke prevention in patients with atrial fibrillation (AF) (dabigatran etexilate, rivaroxaban and apixaban); all demonstrated superiority or non-inferiority compared with warfarin (RE-LY, ARISTOTLE and ROCKET-AF). This study aimed to assess the representativeness for the real-world AF population, particularly the population eligible for anticoagulants.

Design: A cross-sectional database analysis.

Setting: Dataset derived from the General Practice Research Database (GPRD). PRIMARY AND SECONDARY OUTCOMES MEASURE: The proportion of real-world patients with AF who met the inclusion/exclusion criteria for RE-LY, ARISTOTLE and ROCKET-AF were compared. The results were then stratified by risk of stroke using CHADS(2) and CHA(2)DS(2)-VASc.

Results: 83 898 patients with AF were identified in the GPRD. For the population at intermediate or high risk of stroke and eligible for anticoagulant treatment (CHA(2)DS(2)-VASc ≥1; n=78 783 (94%)), the proportion eligible for inclusion into RE-LY (dabigatran etexilate) was 68% (95% CI 67.7% to 68.3%; n=53 640), compared with 65% (95% CI 64.7% to 65.3%; n=51 163) eligible for ARISTOTLE (apixaban) and 51% (95% CI 50.7% to 51.4%; n=39 892) eligible for ROCKET-AF (rivaroxaban). Using the CHADS(2) method of risk stratification, for the population at intermediate or high risk of stroke and eligible for anticoagulation treatment (CHADS(2) ≥1; n=71 493 (85%)), the proportion eligible for inclusion into RE-LY was 74% (95% CI 73.7% to 74.3%; n=52 783), compared with 72% (95% CI 71.7% to 72.3%; n=51 415) for ARISTOTLE and 56% (95% CI 55.6% to 56.4%; n=39 892) for ROCKET-AF.

Conclusions: Patients enrolled within RE-LY and ARISTOTLE were more reflective of the 'real-world' AF population in the UK, in contrast with patients enrolled within ROCKET-AF who were a more narrowly defined group of patients at higher risk of stroke. Differences between trials should be taken into account when considering the applicability of findings from randomised clinical trials. However, assessing representativeness is not a substitute for assessing generalisibility, that is, how well clinical trial results would translate into effectiveness and safety in everyday routine care.