Major bleeding risk and mortality associated with antiplatelet drugs in real-world clinical practice. A prospective cohort study

PLoS One. 2020 Aug 7;15(8):e0237022. doi: 10.1371/journal.pone.0237022. eCollection 2020.

Abstract

Background: Major bleedings other than gastrointestinal (GI) and intracranial (ICH) and mortality rates associated with antiplatelet drugs in real-world clinical practice are unknown. The objective was to estimate major bleeding risk and mortality among new users of antiplatelet drugs in real-world clinical practice.

Methods and findings: A population-based prospective cohort using the French national health data system (SNIIRAM), identified 69,911 adults living within five well-defined geographical areas, who were new users of antiplatelet drugs in 2013-2015 and who had not received any antithrombotics in 2012. Among them, 63,600 started a monotherapy and 6,311 a dual regimen. Clinical data for all adults referred for bleeding was collected from all emergency departments within these areas, and medically validated. Databases were linked using common key variables. The main outcome measure was time to major bleeding (GI, ICH and other bleedings). Secondary outcomes were death, and event-free survival (EFS). Hazard ratios (HR) were derived from adjusted Cox proportional hazard models. We used Inverse Propensity of Treatment Weighting as a stratified sensitivity analysis according to the antiplatelet monotherapy indication: primary prevention without cardiovascular (CV) risk factors, with CV risk factors, and secondary prevention. We observed 250 (0.36%) major haemorrhages, 81 ICH, 106 GI and 63 other types of bleeding. Incidences were twice as high in dual therapy as in monotherapy. Compared to low-dose aspirin (≤ 100 mg daily), high-dose (> 100 up to 325 mg daily) was associated with an increased risk of ICH (HR = 1.80, 95%CI 1.10 to 2.95). EFS was improved by high-dose compared to low-dose aspirin (1.41, 1.04 to 1.90 and 1.32, 1.03 to 1.68) and clopidogrel (1.30, 0.73 to 2.3 and 1.7, 1.24 to 2.34) respectively in primary prevention with and without CV risk factors.

Conclusion: The incidence of major bleeding and mortality was low. In monotherapy, low-dose aspirin was the safest therapeutic option whatever the indication.

Trial registration: NCT02886533.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Aspirin / administration & dosage
  • Aspirin / adverse effects
  • Clopidogrel / administration & dosage
  • Clopidogrel / adverse effects
  • Cohort Studies
  • Databases, Factual
  • Drug Therapy, Combination
  • Female
  • France / epidemiology
  • Gastrointestinal Hemorrhage / chemically induced
  • Gastrointestinal Hemorrhage / epidemiology
  • Gastrointestinal Hemorrhage / mortality
  • Hemorrhage / chemically induced*
  • Hemorrhage / epidemiology
  • Hemorrhage / mortality*
  • Humans
  • Incidence
  • Intracranial Hemorrhages / chemically induced
  • Intracranial Hemorrhages / epidemiology
  • Intracranial Hemorrhages / mortality
  • Male
  • Middle Aged
  • Outcome Assessment, Health Care
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects*
  • Prospective Studies
  • Risk Factors
  • Young Adult

Substances

  • Platelet Aggregation Inhibitors
  • Clopidogrel
  • Aspirin

Associated data

  • ClinicalTrials.gov/NCT02886533
  • figshare/10.6084/m9.figshare.12581999.v1

Grants and funding

This study was supported by the National Clinical Research Hospital Program of the French Ministry of Health (PHRC-12-009-0243). The funder had no role in the study design, data collection, analysis, or interpretation, in the writing of the article, or in the decision to submit it for publication.