Impact of bleeding assessment and adjudication methodology on event rates and clinical trial outcomes: insights from the HORIZONS-AMI trial. Academic Article uri icon

Overview

abstract

  • AIMS: Bleeding is a major safety outcome in cardiovascular trials. The present study assessed the impact of the adjudication process of bleeding events on three-year outcomes in the Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction (HORIZONS-AMI) trial. METHODS AND RESULTS: HORIZONS-AMI enrolled 3,602 patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. An independent CEC reviewed 445 potential bleeding events identified from three sources: 339 site-reported (SR), 35 CEC-identified, and 71 database (DB)-triggered events based on programmatic identification of a decline in haemoglobin of ≥3 g/dL or in haematocrit by ≥9%; of those, 383/445 (86.1%) met the protocol definition of major bleeding. By multivariable analysis, CEC-confirmed bleeding was an independent predictor of cardiovascular death (hazard ratio [HR] 2.84, 95% confidence interval [CI]: 1.81-4.45, p<0.0001) and all-cause death (HR 2.70, 95% CI: 1.92-3.79, p<0.0001) at three years. Non-CEC-confirmed bleeding was also a predictor of cardiovascular death (HR 3.45, 95% CI: 1.47-8.11, p=0.005) and all-cause death (HR 2.41, 95% CI: 1.11-5.23, p=0.03) at three years. CONCLUSIONS: In the HORIZONS-AMI trial, adjudication of bleeding via a centralised CEC process resulted in identification of a larger number of events than were SR. All CEC-confirmed bleeding events were independently predictive of three-year cardiovascular and all-cause mortality. The association of non-CEC-confirmed bleeding with mortality merits further investigation.

publication date

  • August 3, 2018

Research

keywords

  • Myocardial Infarction
  • Percutaneous Coronary Intervention

Identity

Scopus Document Identifier

  • 85051176308

Digital Object Identifier (DOI)

  • 10.4244/EIJ-D-18-00131

PubMed ID

  • 29688176

Additional Document Info

volume

  • 14

issue

  • 5