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High on-treatment platelet reactivity to both aspirin and clopidogrel is associated with the highest risk of adverse events following percutaneous coronary intervention
  1. Nicoline J Breet1,2,
  2. Jochem W van Werkum1,2,
  3. Heleen J Bouman1,2,
  4. Johannes C Kelder1,2,
  5. Ankie M Harmsze3,
  6. Christian M Hackeng2,4,
  7. Jurriën M ten Berg1,2
  1. 1Department of Cardiology, St Antonius Hospital, Nieuwegein, The Netherlands
  2. 2St Antonius Center for Platelet Function research, Nieuwegein, The Netherlands
  3. 3Department of Clinical Pharmacy, St Antonius Hospital, Nieuwegein, The Netherlands
  4. 4Department of Clinical Chemistry, St Antonius Hospital, Nieuwegein, The Netherlands
  1. Correspondence to Jurrien M ten Berg, Department of Cardiology, St Antonius Hospital, P O Box 2500, 3435 CM Nieuwegein, The Netherlands; j.ten.berg{at}


Aim High on-clopidogrel platelet reactivity (HCPR) and high on-aspirin platelet reactivity (HAPR) are associated with atherothrombotic events following coronary stenting. There are, however, few data concerning high on-treatment platelet reactivity to both aspirin and clopidogrel simultaneously. The aim of the present study was to determine the incidence of dual high on-treatment platelet reactivity (DAPR) and its impact on clinical outcome.

Methods On-treatment platelet reactivity was measured in parallel by ADP- and arachidonic acid-induced light transmittance aggregometry (LTA) (n=921) and the point-of-care VerifyNow system (P2Y12 and aspirin) (n=422) in patients on dual antiplatelet therapy undergoing elective stent implantation. HCPR and HAPR were established by receiver-operator characteristic curve analysis. The primary endpoint was a composite of all-cause death, non-fatal acute myocardial infarction, stent thrombosis and ischaemic stroke at 1-year follow-up.

Results The incidence of DAPR varied between 14.7% and 26.9% depending on the platelet function test used. DAPR, assessed by LTA and the VerifyNow system, was highly associated with an adverse clinical outcome. At 1-year follow-up the primary endpoint occurred more frequently in patients with isolated HCPR (11.7%), isolated HAPR (9.6%) or DAPR (10.7%) compared with patients without high on-treatment platelet reactivity (4.2%, all p<0.01) when platelet function was evaluated with LTA. Using the VerifyNow system, patients exhibiting DAPR had the highest risk for the primary endpoint (17.7% vs 4.1% in patients without high on-treatment platelet reactivity, p=0.001).

Conclusions In patients undergoing elective percutaneous coronary intervention, DAPR to aspirin and clopidogrel is present in one in five patients and is associated with a high risk for atherothrombotic events. DAPR measured by the point-of-care VerifyNow system has a higher predictability for atherothrombotic events than LTA.

Clinical Trial Registration Information NCT00352014.

  • Coronary intervention
  • antiplatelet treatment

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  • Competing interests NJB has received a speaker's fee from Siemens; JWvW has received a speaker's fee from Accumetrics and Siemens and a consultancy fee from the Medicines Company; JMtB has received a speaker's fee from Sanofi-Aventis, Eli Lilly, BMS and MSD and consultancy fees from Sanofi-Aventis, Eli Lilly, Schering-Plough and Glaxo Smith Kline. None of the other authors report financial disclosures.

  • Ethics approval This study was conducted with the approval of the Verenigde Commissie Mensgebonden Onderzoek (VCMO), St Antonius Ziekenhuis, Nieuwegein.

  • Provenance and peer review Not commissioned; externally peer reviewed.