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

Abstract

BACKGROUND:

The GRAVITAS trial showed that 150 mg 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 150 mg 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 24 h 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 150 mg clopidogrel after 4 weeks. After control platelet function measurements at day 28, 75 mg clopidogrel was administered to all patients until 1 year.

RESULTS:

The study was prematurely terminated at the stage of 200 enroled patients. Administration of 150 mg 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 75 mg 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 1 year.

CONCLUSIONS:

One-month administration of 150 mg 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.

• Authors: Dániel Aradi, Orsolya Rideg, András Vorobcsuk, Tamás Magyarlaki, Balázs Magyari, Attila Kónyi, Tünde Pintér, Iván G Horváth, András Komócsi
• Journal: European journal of clinical investigation (Eur J Clin Invest) Vol. 42 Issue 4 Pg. 384-92 (Apr 2012) ISSN: 1365-2362 [Electronic] England
• PMID: 21902692 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 The Authors. European Journal of Clinical Investigation © 2011 Stichting European Society for Clinical Investigation Journal Foundation.

Chemical References

• Cell Adhesion Molecules
• Microfilament Proteins
• Phosphoproteins
• Platelet Aggregation Inhibitors
• vasodilator-stimulated phosphoprotein
• Clopidogrel
• Ticlopidine

Topics

• Aged
• Angina, Stable (drug therapy)
• Blood Platelets (drug effects)
• Cell Adhesion Molecules (drug effects)
• Clopidogrel
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Follow-Up Studies
• Humans
• Kaplan-Meier Estimate
• Male
• Microfilament Proteins (drug effects)
• Middle Aged
• Phosphoproteins (drug effects)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (administration & dosage)
• Platelet Function Tests
• Stroke (prevention & control)
• Thrombosis (prevention & control)
• Ticlopidine (administration & dosage, analogs & derivatives)
• Time Factors