Details

Autor(en) / Beteiligte

• Giugliano, Robert P., MD, SM
• Ruff, Christian T., MD, MPH
• Wiviott, Stephen D., MD
• Nordio, Francesco, PhD
• Murphy, Sabina A., MPH
• Kappelhof, Johannes AN., BSc
• Shi, Minggao, PhD
• Mercuri, Michele, MD
• Antman, Elliott M., MD
• Braunwald, Eugene, MD

Titel

Mortality in Patients With Atrial Fibrillation Randomized to Edoxaban or Warfarin: Insights from the ENGAGE AF-TIMI 48 Trial

Ist Teil von

• The American journal of medicine, 2016-08, Vol.129 (8), p.850-857.e2

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2016

Quelle

Access via ScienceDirect (Elsevier)

Beschreibungen/Notizen

• Abstract Background When compared with warfarin, edoxaban significantly reduced cardiovascular mortality in the ENGAGE AF-TIMI 48 trial. We studied the possible reasons leading to this reduction. Methods ENGAGE AF-TIMI 48 was a double-blind, double-dummy comparison of warfarin with 2 regimens of once-daily edoxaban in 21,105 patients with atrial fibrillation followed for 2.8 years (median). Causes of deaths in the intention-to-treat population were classified as cardiovascular (including fatal bleeding and ischemic stroke), malignancy, or non-cardiovascular/non-malignancy by an independent, blinded, clinical endpoint committee . Deaths also were adjudicated as directly due to bleeding (i.e., fatal), or bleeding contributing to death, or neither. Results There were 839 total deaths (4.35%/yr) in the warfarin arm, compared with 773 (3.99%/yr, p=0.08) with the higher-dose edoxaban regimen, and 737 (3.80%/yr, p=0.006) with the lower-dose edoxaban regimen. No significant differences between treatments were observed in: 1) any of the 3 most common causes of cardiovascular death (sudden cardiac, heart failure, ischemic stroke), 2) fatal malignancies, 3) other non-cardiovascular death. There were 124 fatal bleeds, 65 with warfarin, significantly fewer with the higher-dose (n=35, p=0.003) and lower-dose (n=24, p<0.001) edoxaban regimens. There were 101 bleeding events with warfarin that were either fatal or that contributed to death. There were significantly fewer with the higher-dose (n=59, P=0.001) and lower-dose (n=54, P<0.001) edoxaban regimens. Conclusions Fewer total and cardiovascular deaths were observed with edoxaban as compared to warfarin in the ENGAGE AF-TIMI 48 trial, and this predominantly resulted from significantly lower rate of major bleeding with edoxaban. Edoxaban reduces mortality both directly (less fatal bleeding) and indirectly (fewer bleeding-related complications and interruptions in therapy after non-fatal bleeding).