A randomized trial of platelet reactivity monitoring-adjusted clopidogrel therapy versus prasugrel therapy to reduce high on-treatment platelet reactivity

Int J Cardiol. 2013 Oct 9;168(4):4244-8. doi: 10.1016/j.ijcard.2013.07.147. Epub 2013 Aug 2.

Abstract

Background: Peri-procedural platelet reactivity (PR) inhibition is critical in patients undergoing percutaneous coronary intervention (PCI). High on-treatment PR (HTPR) was associated with recurrent ischemic events in acute coronary syndrome (ACS) patients undergoing PCI. We aimed to compare a strategy of clopidogrel loading dose-adjustment (CDA) according to PR monitoring with standard prasugrel therapy to reduce the rate of patients exhibiting HTPR.

Methods: We enrolled 177 ACS patients in a prospective multicentre randomized trial comparing CDA according to PR monitoring and prasugrel therapy. The VASP index was used to measure PR and a VASP ≥ 50% defined HTPR. The primary endpoint of the study was the rate of HTPR on discharge.

Results: Baseline characteristics of the CDA group (n = 88) and of the prasugrel group (n = 89) were similar. CDA significantly reduced PR and the rate of HTPR compared to a single LD of clopidogrel (30.9 ± 13.9%; p < 0.0001 and 43 to 2.3%; p < 0.001, respectively). Following CDA the rate of patients with HTPR was significantly lower in the CDA group compared to the prasugrel group on discharge (2.3 vs 15.7%; p = 0.005). In addition fewer patients in the CDA group had a VASP < 16% on discharge (14.7 vs 50.5%; p <0.0001).

Conclusion: In the present study, PR monitoring was superior to standard prasugrel therapy to reduce the rate of HTPR in ACS patients. In addition such strategy reduced the number of patients with very low PR.

Keywords: Acute coronary syndrome; Bleeding; Platelet reactivity monitoring; Stent thrombosis; VASP.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Blood Platelets / drug effects
  • Blood Platelets / metabolism
  • Clopidogrel
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Piperazines / pharmacology
  • Piperazines / therapeutic use*
  • Platelet Activation / drug effects*
  • Platelet Activation / physiology*
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prasugrel Hydrochloride
  • Prospective Studies
  • Purinergic P2Y Receptor Antagonists / pharmacology
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Single-Blind Method
  • Thiophenes / pharmacology
  • Thiophenes / therapeutic use*
  • Ticlopidine / analogs & derivatives*
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use
  • Treatment Outcome

Substances

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