Incorporation of bleeding as an element of the composite end point in clinical trials of antithrombotic therapies in patients with non-ST-segment elevation acute coronary syndrome: validity, pitfalls, and future approaches

Am Heart J. 2013 May;165(5):644-54, 654.e1. doi: 10.1016/j.ahj.2012.11.012. Epub 2013 Feb 13.

Abstract

With the large number of antithrombotic therapies available and under investigation for the treatment of non-ST-segment elevation acute coronary syndromes (NSTE ACS), practice guidelines now stress the importance of selecting an antithrombotic strategy according to the efficacy and safety profiles of the chosen agent. Contemporary trials have incorporated bleeding along with ischemic end points into a composite end point commonly referred to as net clinical benefit, which allows for simultaneous evaluation of the differences between benefit and harm for an investigational antithrombotic therapy. However, incorporating major bleeding into a composite end point that includes ischemic events is not warranted and is associated with many pitfalls. In this article, we discuss the validity of combining efficacy and safety end points to form a net clinical benefit composite end point with the traditional time-to-event analysis for trials evaluating antithrombotic therapies for NSTE ACS. We describe alternative statistical approaches for concurrent assessment of the safety and efficacy of antithrombotic therapies used to treat patients with NSTE ACS.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / physiopathology
  • Anticoagulants / adverse effects*
  • Anticoagulants / therapeutic use
  • Clinical Trials as Topic*
  • Electrocardiography*
  • Hemorrhage* / blood
  • Hemorrhage* / chemically induced
  • Hemorrhage* / epidemiology
  • Humans
  • Incidence
  • Platelet Aggregation Inhibitors / adverse effects*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prognosis
  • Survival Rate

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors