High rates of prasugrel and ticagrelor non-responder in patients treated with therapeutic hypothermia after cardiac arrest

Resuscitation. 2014 May;85(5):649-56. doi: 10.1016/j.resuscitation.2014.02.004. Epub 2014 Feb 17.


Introduction: After cardiac arrest due to acute coronary syndromes (ACS) therapeutic hypothermia (HT) is the standard care to reduce neurologic damage. Additionally, the concomitant medical treatment with aspirin and a P2Y12 receptor inhibitor like clopidogrel (Cl), prasugrel (Pr) or ticagrelor (Ti) is mandatory. The platelet inhibitory effect of these drugs under hypothermia remains unclear.

Methods: 164 patients with ACS were prospectively enrolled in this study. 84 patients were treated with HT, 80 patients were under normothermia (NT). All patients were treated with aspirin and one of the P2Y12 receptor inhibitors Cl, Pr or Ti. 24h after the initial loading dose the platelet reactivity index (PRI/VASP-index) was determined to achieve the platelet inhibitory effect.

Results: In the HT-group the PRI/VASP-index was significantly higher compared to the NT-group (54.86%±25.1 vs. 28.98%±22.8; p<0.001). In patients under HT receiving Cl, the platelet inhibition was most markedly reduced (HT vs. NT: 66.39%±19.1 vs. 33.36%±22.1; p<0.001) compared to Pr (HT vs. NT: 37.6%±25.0 vs. 27.04%±25.5; p=0.143) and Ti (HT vs. NT: 41.5%±21.0 vs. 17.83%±14.5; p=0.009). The rate of non-responder defined as PRI/VASP-index>50% was increased in HT compared to NT (60.7% vs. 22.5%; p<0.001) with the highest rates in the group receiving Cl (CL: 82% vs. 26%, p<0.001; Pr: 32% vs. 23%; n.s.; Ti: 30% vs. 8%, n.s.).

Conclusion: The platelet inhibitory effect in patients treated with HT after cardiac arrest is significantly reduced. This effect was most marked with the use of Cl. The new P2Y12-inhibitors Pr and Ti improved platelet inhibition in HT, but could not completely prevent non-responsiveness.

Keywords: Clopidogrel; Non-responder; Prasugrel; Therapeutic hypothermia; Ticagrelor.

Publication types

  • Observational Study

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / therapeutic use
  • Clopidogrel
  • Female
  • Flow Cytometry
  • Heart Arrest / therapy*
  • Humans
  • Hypothermia, Induced*
  • Male
  • Middle Aged
  • Piperazines / therapeutic use*
  • Platelet Aggregation Inhibitors / therapeutic use
  • Prasugrel Hydrochloride
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Risk Factors
  • Thiophenes / therapeutic use*
  • Ticagrelor
  • Ticlopidine / analogs & derivatives
  • Ticlopidine / therapeutic use
  • Treatment Outcome


  • Piperazines
  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists
  • Thiophenes
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor
  • Adenosine
  • Ticlopidine