Many challenges are observed in the contemporary management of atrial fibrillation (AF). In patients with AF, anticoagulation involves a careful balance between maximizing the benefit with respect to the prevention of stroke while minimizing the bleeding risk. Several novel oral anticoagulants have been approved and released on the market as alternatives to warfarin in recent years; in a meta?analysis, the novel oral anticoagulants significantly reduced stroke/systemic embolic event (SEE), mortality and intracranial haemorrhage (ICH), while gastrointestinal bleeding was increased.
The ENGAGE AF?TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation?Thrombolysis in Myocardial Infarction 48) Trial was a 3?arm, randomized, double?blind, double?dummy trial comparing 2 once?daily dose regimens of edoxaban (higher dose [60 mg] and lower dose [30 mg]) to warfarin with respect to the prevention of stroke or systemic embolism in patients with AF.
The impact of different types of extracranial bleeding events on health?related quality of life and health?state utility among patients with atrial fibrillation is studied.
The ENGAGE AF?TIMI 48 (Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48) Trial compared edoxaban with warfarin with respect to the prevention of stroke or systemic embolism in atrial fibrillation. Data from the EuroQol?5D (EQ?5D?3L) questionnaire, prospectively collected at 3?month intervals for up to 48 months, were used to estimate the impact of different categories of bleeding events on health?state utility over 12 months following the event.
Compared with clinically relevant nonmajor and minor bleeds, major gastrointestinal and non-gastrointestinal bleeds were associated with larger immediate decrements in utility scores that decreased gradually over the year following the bleeding event and were no longer statistically significant at 12 months.
Longitudinal mixed?effect models revealed that major gastrointestinal bleeds and major nongastrointestinal bleeds were associated with significant immediate decreases in utility scores (−0.029 [−0.044 to −0.014; P<0.001] and −0.029 [−0.046 to −0.012; P=0.001], respectively).
These effects decreased in magnitude over time, and were no longer significant for major nongastrointestinal bleeds at 9 months, but remained borderline significant for major gastrointestinal bleeds at 12 months.
Clinically relevant nonmajor and minor bleeds were associated with smaller but measurable immediate impacts on utility (−0.010 [−0.016 to −0.005] and −0.016 [−0.024 to −0.008]; P<0.001 for both), which remained relatively constant and statistically significant over the 12 months following the bleeding event.
Bleeding is the most common complication associated with anticoagulation management in patients with AF. All categories of bleeding events were associated with significant immediate decreases in EQ?5D utility and negative impacts on health?state utility in patients with atrial fibrillation.
Major bleeds were associated with relatively large immediate decreases in utility scores that gradually diminished over 12 months; clinically relevant nonmajor and minor bleeds were associated with smaller immediate decreases in utility that persisted over 12 months.