Effectiveness of Antiplatelet Drugs Under Therapeutic Hypothermia: A Comprehensive Review

Clin Pharmacol Ther. 2019 Nov;106(5):993-1005. doi: 10.1002/cpt.1492. Epub 2019 Jul 1.


Out-of-hospital cardiac arrest is among the most frequent causes of death worldwide. Immediate intervention, as well as dual antiplatelet therapy consisting of acetylsalicylic acid and a P2Y12 inhibitor is often recommended. In line with the growing number of reports on cardiac arrest treatment, therapeutic hypothermia (TH) has been proposed for unconscious patients to improve neurological outcomes. Nevertheless, studies report controversial and often discrepant results on the effect of hypothermia on blood coagulability and platelet reactivity. In this review, we summarize the knowledge on platelet function under diverse hypothermic conditions. Additionally, we review the current literature on the effect of systemic hypothermia on pharmacokinetic and pharmacodynamic properties of antiplatelet agents. It has been shown that TH can alter the effectiveness of antiplatelet agents, including P2Y12 inhibitors, through multiple mechanisms, hence, special attention should be paid while implementing antiplatelet therapy in patients under TH conditions.

Publication types

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

MeSH terms

  • Aspirin / pharmacology
  • Blood Coagulation / physiology
  • Blood Coagulation Tests
  • Blood Platelets / metabolism
  • Body Temperature / physiology*
  • Combined Modality Therapy
  • Cytochrome P-450 Enzyme System / metabolism
  • Drug Interactions
  • Drug Monitoring / methods
  • Humans
  • Hypothermia, Induced / methods*
  • Inflammation / etiology
  • Inflammation / therapy
  • Inflammation Mediators / metabolism
  • Myocardial Reperfusion Injury / prevention & control
  • Out-of-Hospital Cardiac Arrest / complications
  • Out-of-Hospital Cardiac Arrest / therapy*
  • Platelet Aggregation Inhibitors / pharmacokinetics
  • Platelet Aggregation Inhibitors / pharmacology*
  • Platelet Function Tests
  • Purinergic P2Y Receptor Antagonists / pharmacology


  • Inflammation Mediators
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Cytochrome P-450 Enzyme System
  • Aspirin