Edoxaban effective, safe across full SBP range in high-risk AF patients
The efficacy and safety of the novel oral anticoagulant (NOAC) edoxaban relative to warfarin for stroke prophylaxis are consistent across the full range of systolic blood pressure (SBP) in high-risk patients with atrial fibrillation (AF), according to a posthoc analysis of the ENGAGE AF-TIMI 48* trial.
“The findings were similar when patients were stratified by average diastolic blood pressure (DBP), with one exception—the reduction in major bleeding with the higher dose edoxaban regimen (HDER; 60/30 mg) was most pronounced in patients with elevated DBP,” the authors said.
In the present analysis, a total of 19,679 AF patients with hypertension were grouped according to average SBP and DBP. Most of the patients had an average SBP of 120 to <130 mm Hg (n=6,531; 33 percent) and average DBP of 75 to <85 mm Hg (n=9,813; 50 percent).
The primary efficacy endpoint of stroke/systemic embolic event occurred twice as frequently in the group of patients with elevated vs lower average SBP (≥150 vs 130–139 mm Hg: hazard ratio [HR], 2.01, 95 percent CI, 1.50–2.70) or DBP (≥90 vs 75 to <85 mm Hg: HR, 2.36, 1.76–3.16). [Hypertension 2019;74:597-605]
Compared with warfarin, HDER reduced stroke events across the full range of SBP (highest average: HR, 0.75, 0.39–1.46; lowest average: HR, 0.65, 0.24–1.78; p-interaction=0.55) and DBP (highest average: HR, 0.61, 0.27–1.40; lowest average: HR, 0.28, 0.06–1.34; p-interaction=0.44).
In terms of safety, HDER cut the risk of major bleeding events, including intracranial haemorrhage, likewise without modification by average SBP (p-interaction=0.29). However, the authors noted a more complex relationship between treatment arms, major bleeding and average DBP (p-interaction=0.007). Specifically, HDER was neutral compared with warfarin for major bleeding events among patients with low average DBP but conferred significant protection among patients with ≥75 mm Hg (75 to <85 mm Hg; HR, 0.60, 0.48–0.76; p<0.001).
Generally, patients with higher SBP were older, more likely women, and had higher CHADS2 and HASBLED scores, whereas those with higher DBP were younger, had higher creatinine clearance, were less likely to have diabetes, and more often had a history of congestive heart failure, coronary artery bypass graft surgery or percutaneous coronary intervention.
“As the 2017 Hypertension Clinical Practice Guidelines recommended a strict BP treatment goal of <130/80 mm Hg, it is important to note that our analysis showed similar efficacy for stroke/SEE and major bleeding events in [individuals] with average BP >130/80 mm Hg without any effect modification,” the authors noted. [J Am Coll Cardiol 2018;71:e127-e248]
“[The present data] suggests that the efficacy and safety of edoxaban is maintained in hypertensive AF patients even when BP is uncontrolled above the recently recommended BP target,” they added.
Meanwhile, the authors pointed out that it is not possible to establish whether DBP influences the safety profile of edoxaban (or other DOACS) or whether the safety benefit seen among patients with elevated DBP should be attributed to the play of chance.
“The consistent efficacy and safety of edoxaban across the full range of BP levels observed here may be of importance to clinicians managing patients with AF and elevated risk of stroke,” although these may not be generalizable to all patients with AF seen during routine clinical practice, as the age and risk profiles of the ENGAGE AF-TIMI 48 population were relatively high, the authors said.
*Effective Anticoagulation With Factor Xa Next Generation in Atrial Fibrillation–Thrombolysis in Myocardial Infarction 48