High On-Treatment Platelet Reactivity: Aspirin versus Clopidogrel

Pharmacology. 2023;108(1):83-89. doi: 10.1159/000527816. Epub 2022 Dec 2.

Abstract

Background: Antithrombotic regimen in patients on oral anticoagulation (OAC) post-percutaneous coronary intervention (PCI) is challenging. At least, one antiplatelet agent in combination with OAC is recommended after PCI for 6-12 months. Clopidogrel is used most frequently in this setting. However, data comparing P2Y12 inhibition with clopidogrel versus cyclooxygenase inhibition by acetylsalicylic acid (ASA, aspirin) is missing. It is well known that the antiplatelet effects of ASA and clopidogrel are frequently impaired (high on-treatment platelet reactivity [HTPR]). In this pilot investigation, we compared the antiplatelet effects of clopidogrel versus ASA.

Methods: In this retrospective single-center database analysis, we investigated platelet reactivity by light transmission aggregometry in patients under different antiplatelet regimes. Results were presented as maximum of aggregation (MoA). HTPR to ASA and to clopidogrel were assessed.

Results: 755 patients were enrolled. 677 were on ASA, 521 were on clopidogrel, and 198 had OAC. Overall mean age was 73 ± 13.4 years, and 458 (60.7%) were male. HTPR to ASA occurred in 94/677 patients (13.9%), and mean arachidonic acid-induced MoA was 14.15 ± 19.04%. HTPR to clopidogrel occurred in 241/521 patients (46.3%), and mean adenosine diphosphate-induced MoA was 50.06 ± 20.42%. HTPR to clopidogrel was significantly more frequent than HTPR to ASA; single antiplatelet therapy (SAPT)-mono ASA: 27/199 (13.6%) versus mono clopidogrel: 6/18 (33.3%); p = 0.037; SAPT with OAC-OAC with ASA: 8/35 (22.9%) versus OAC with clopidogrel: 27/60 (45%); p = 0.046. Same difference in HTPR contingency could be shown in subgroups of dual antiplatelet therapy and ASA + clopidogrel + OAC therapy.

Conclusion: Impaired pharmacodynamic response to clopidogrel was more frequent as HTPR to ASA. Hence, ASA should be tested in combination with OAC post-PCI.

Keywords: Anticoagulation; Aspirin; Clopidogrel; High on-treatment platelet reactivity; Platelet function.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Aspirin* / pharmacology
  • Aspirin* / therapeutic use
  • Blood Platelets
  • Clopidogrel
  • Female
  • Humans
  • Male
  • Middle Aged
  • Percutaneous Coronary Intervention* / adverse effects
  • Platelet Aggregation
  • Platelet Aggregation Inhibitors / pharmacology
  • Platelet Aggregation Inhibitors / therapeutic use
  • Retrospective Studies
  • Ticlopidine / pharmacology
  • Ticlopidine / therapeutic use

Substances

  • Clopidogrel
  • Aspirin
  • Ticlopidine
  • Platelet Aggregation Inhibitors