Impact of On-Clopidogrel Platelet Reactivity on Incidence of Hypoattenuated Leaflet Thickening After Transcatheter Aortic Valve Replacement

JACC Cardiovasc Interv. 2019 Jan 14;12(1):12-18. doi: 10.1016/j.jcin.2018.08.008. Epub 2018 Aug 27.

Abstract

Objectives: To assess the impact of on-clopidogrel platelet reactivity (PR) on HALT, the authors prospectively tested whether patients with below-median on-clopidogrel PR have a lower incidence of HALT compared with those with above-median on-clopidogrel PR.

Background: It is unclear whether the apparent ineffectiveness of clopidogrel in preventing hypoattenuated leaflet thickening (HALT) after transcatheter aortic valve replacement (TAVR) questions the concept of P2Y12 inhibition after TAVR or is a consequence of an inadequate response to clopidogrel in elderly patients with severe aortic stenosis.

Methods: Patients were either on long-term dual antiplatelet therapy with clopidogrel and acetylsalicylic acid or were given bolus doses of both drugs the day before TAVR. Adenosine diphosphate (ADP)-induced multielectrode impedance aggregometry was performed before TAVR. After TAVR, clopidogrel was continued in all patients. Computed tomographic angiography was performed to detect HALT.

Results: Of 331 patients enrolled, computed tomographic angiography was performed in 200 at 5 days (interquartile range: 4 to 6 days). Among patients with below-median ADP-induced PR (<180 AU · min), 16 were diagnosed with HALT, whereas 20 patients with above-median PR were diagnosed with HALT (p = 0.58). Among patients with high on-clopidogrel PR (>468 AU · min; n = 29), 7 (24%) displayed HALT, compared with 19 (17%) with ADP-induced PR ≤468 AU · min (p = 0.43). Consistently, ADP-induced PR as a continuous variable was not significantly associated with HALT (p = 0.75). Oral anticoagulation was associated with reduced rates of HALT (odds ratio: 0.41; 95% CI: 0.18 to 0.96; p = 0.04).

Conclusions: On-clopidogrel ADP-induced PR was not significantly associated with the occurrence of HALT. In contrast, oral anticoagulation was associated with reduced rates of HALT.

Keywords: HALT; TAVR; antiplatelet therapy; leaflet thrombosis; platelets.

Publication types

  • Comparative Study
  • Observational Study

MeSH terms

  • Administration, Oral
  • Aged
  • Aged, 80 and over
  • Anticoagulants / administration & dosage
  • Aortic Valve / diagnostic imaging
  • Aortic Valve / drug effects*
  • Aortic Valve / surgery*
  • Clopidogrel / administration & dosage*
  • Clopidogrel / adverse effects
  • Drug Resistance
  • Female
  • Germany / epidemiology
  • Humans
  • Incidence
  • Male
  • Platelet Aggregation / drug effects*
  • Platelet Aggregation Inhibitors / administration & dosage*
  • Platelet Aggregation Inhibitors / adverse effects
  • Postoperative Complications / blood
  • Postoperative Complications / diagnostic imaging
  • Postoperative Complications / epidemiology*
  • Postoperative Complications / prevention & control
  • Prospective Studies
  • Protective Factors
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Transcatheter Aortic Valve Replacement / adverse effects*
  • Treatment Outcome

Substances

  • Anticoagulants
  • Platelet Aggregation Inhibitors
  • Clopidogrel