Clinical consequences of bleeding among individuals with a recent acute coronary syndrome: Insights from the APPRAISE-2 trial

Am Heart J. 2019 Sep;215:106-113. doi: 10.1016/j.ahj.2019.05.004. Epub 2019 May 11.

Abstract

Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events.

Methods: In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models.

Results: In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14).

Conclusions: In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding.

Trial registration: ClinicalTrials.gov NCT00831441.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Aspirin* / administration & dosage
  • Aspirin* / adverse effects
  • Double-Blind Method
  • Drug Interactions
  • Drug Therapy, Combination / methods
  • Factor Xa Inhibitors / administration & dosage
  • Factor Xa Inhibitors / adverse effects
  • Female
  • Hemorrhage* / chemically induced
  • Hemorrhage* / diagnosis
  • Hemorrhage* / mortality
  • Hemorrhage* / prevention & control
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / drug therapy*
  • Outcome and Process Assessment, Health Care
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Proportional Hazards Models
  • Pyrazoles* / administration & dosage
  • Pyrazoles* / adverse effects
  • Pyridines* / administration & dosage
  • Pyridines* / adverse effects
  • Pyridones* / administration & dosage
  • Pyridones* / adverse effects
  • Risk Assessment
  • Risk Factors
  • Thrombolytic Therapy* / adverse effects
  • Thrombolytic Therapy* / methods

Substances

  • Factor Xa Inhibitors
  • Platelet Aggregation Inhibitors
  • Pyrazoles
  • Pyridines
  • Pyridones
  • thienopyridine
  • apixaban
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT00831441