Bleeding and ischaemic outcomes in patients treated with dual or triple antithrombotic therapy: systematic review and meta-analysis

Eur Heart J Cardiovasc Pharmacother. 2019 Oct 1;5(4):226-236. doi: 10.1093/ehjcvp/pvz021.

Abstract

Aims: The combination of oral anticoagulation with a P2Y12 inhibitor and aspirin in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI) is associated with a high bleeding risk. Dual antithrombotic therapy (DAT) with omission of aspirin is a promising option to reduce bleedings, but carries a yet unknown risk of ischaemic events. We therefore sought to systematically review and analyse randomized controlled trials investigating DAT vs. triple antithrombotic therapy (TAT) in patients with AF following PCI and/or acute coronary syndrome (ACS).

Methods and results: We included four trials with overall 9317 patients (5039 DAT, 4278 TAT) in our analysis. Dual antithrombotic therapy was associated with a significant reduction in thrombolysis in myocardial infarction major bleeding [hazard ratio (HR) 0.52, 95% confidence interval (CI) 0.42-0.65; P = 0.0001], while the composite trial-defined ischaemic endpoint did not differ significantly between DAT and TAT (HR 0.98, 95% CI 0.79-1.22; P = 0.88). There was also no difference regarding the occurrence of myocardial infarction (MI; HR 1.16, 95% CI 0.92-1.46; P = 0.21) or stent thrombosis (HR 1.25, 95% CI 0.69-2.26; P = 0.46). Absolute numbers for MI were 131/4278 (3.1%) with TAT and 182/5039 (3.6%) with DAT, and for stent thrombosis 32/4278 (0.75%) and 52/5039 (1%), respectively. A post hoc power calculation based on the size and event rate of this meta-analysis revealed 80% power to detect a 37% and 100% increase in MI and stent thrombosis, respectively.

Conclusion: Dual antithrombotic therapy significantly reduces bleedings compared with TAT and seems to have a similar effect in preventing ischaemic endpoints in AF patients post-PCI or ACS. Future investigations are needed to determine its applicability specifically in patients at high risk of ischaemic outcomes.

Keywords: Acute coronary syndrome; Antithrombotic therapy; Atrial fibrillation; Percutaneous coronary intervention.

Publication types

  • Meta-Analysis
  • Systematic Review

MeSH terms

  • Acute Coronary Syndrome / diagnosis
  • Acute Coronary Syndrome / epidemiology
  • Acute Coronary Syndrome / therapy*
  • Anticoagulants / administration & dosage*
  • Anticoagulants / adverse effects
  • Atrial Fibrillation / diagnosis
  • Atrial Fibrillation / drug therapy*
  • Atrial Fibrillation / epidemiology
  • Coronary Artery Disease / diagnosis
  • Coronary Artery Disease / epidemiology
  • Coronary Artery Disease / therapy*
  • Coronary Thrombosis / epidemiology
  • Coronary Thrombosis / prevention & control*
  • Drug Therapy, Combination
  • Female
  • Fibrinolytic Agents / administration & dosage*
  • Fibrinolytic Agents / adverse effects
  • Hemorrhage / chemically induced
  • Humans
  • Male
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / prevention & control*
  • Percutaneous Coronary Intervention* / adverse effects
  • Percutaneous Coronary Intervention* / instrumentation
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects*
  • Randomized Controlled Trials as Topic
  • Risk Assessment
  • Risk Factors
  • Stents
  • Treatment Outcome

Substances

  • Anticoagulants
  • Fibrinolytic Agents
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists