Justification of 150mg clopidogrel in patients with high on-clopidogrel platelet reactivity

Dániel Aradi, Orsolya Rideg, András Vorobcsuk, Tamás Magyarlaki, Balázs Magyari, Attila Kónyi, Tünde Pintér, Iván G. Horváth, András Komócsi

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Abstract

Background The GRAVITAS trial showed that 150mg clopidogrel did not improve outcome in patients with high on-clopidogrel platelet reactivity (HPR) screened by the VerifyNow assay. We aimed to determine the impact of 150mg clopidogrel in stable angina patients with HPR identified with conventional aggregometry (LTA). Materials and methods Clopidogrel-naive stable angina patients before ad hoc percutaneous coronary intervention were recruited into a randomized, double-blind, placebo-controlled trial (NCT00638326). Twelve to 24h after the 600-mg loading dose of clopidogrel, ADP 5μM-stimulated maximal (AGGmax), late platelet aggregation (AGGlate) and vasodilator-stimulated phosphoprotein phosphorylation (VASP-PRI) were evaluated. Patients with HPR (AGGmax≥34%) were randomly allocated to 75 or 150mg clopidogrel after 4weeks. After control platelet function measurements at day 28, 75mg clopidogrel was administered to all patients until 1year. Results The study was prematurely terminated at the stage of 200 enroled patients. Administration of 150mg clopidogrel significantly reduced platelet aggregation (AGGmax: 45·0±6·8 vs. 33·8±15·1, P<0·01; AGGlate: 27·1±14·7 vs. 13·8±18·0, P<0·01) and VASP-PRI (57·5±15·2 vs. 37·2±17·1; P<0·01), while platelet reactivity remained unchanged in patients with HPR receiving 75mg clopidogrel. The higher maintenance dose of clopidogrel was associated with a significant reduction in cardiovascular (CV) death and myocardial infarction (MI) (0% vs. 11·4%, P=0·04) and in CV death, MI or target vessel revascularization (24·6% vs. 3·1%; P=0·01) during 1year. Conclusions One-month administration of 150mg maintenance dose of clopidogrel reduces platelet reactivity and might decrease the risk of thrombo-ischaemic complications in stable angina patients with HPR identified by LTA.

Original languageEnglish
Pages (from-to)384-392
Number of pages9
JournalEuropean Journal of Clinical Investigation
Volume42
Issue number4
DOIs
Publication statusPublished - Apr 1 2012

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Keywords

  • Clopidogrel
  • High platelet reactivity
  • Outcome
  • Percutaneous coronary intervention

ASJC Scopus subject areas

  • Biochemistry
  • Clinical Biochemistry

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