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  • Title: High-dose atorvastatin on the pharmacodynamic effects of double-dose clopidogrel in patients undergoing percutaneous coronary interventions: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study.
    Author: Leoncini M, Toso A, Maioli M, Angiolillo DJ, Giusti B, Marcucci R, Abbate R, Bellandi F.
    Journal: JACC Cardiovasc Interv; 2013 Feb; 6(2):169-79. PubMed ID: 23428009.
    Abstract:
    OBJECTIVES: The goal of this study was to investigate the impact of high-dose atorvastatin on the pharmacodynamic (PD) effects of double-dose clopidogrel in statin-naive patients with stable coronary artery disease (CAD) and high-on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel before percutaneous coronary intervention (PCI). BACKGROUND: Patients with HTPR are at increased risk of adverse cardiovascular events after PCI. High-dose statins improve prognosis in high-risk patients by lipid- and nonlipid-related mechanisms, including antithrombotic effects. METHODS: The ACHIDO (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity) study was a randomized PD study of high-dose (80 mg) atorvastatin in addition to double-dose (150 mg) clopidogrel (atorvastatin group, n = 38) versus double-dose clopidogrel alone (control group, n = 38) in patients with HTPR. HTPR was defined as P2Y(12) reaction units (PRU) ≥235 by the VerifyNow P2Y12 assay. Platelet reactivity was evaluated immediately before PCI and at 10 and 30 days. RESULTS: Patients randomized to atorvastatin had lower PRU values (188 ± 48 vs. 223 ± 53 PRU, p < 0.01; primary endpoint) and HTPR rates (16% vs. 42%, p < 0.01) at 30 days than patients in the control group. Statin treatment (odds ratio [OR]: 3.8, p = 0.011), baseline PRU <298 (OR: 10.7, p = 0.0001), noncarrier status of CYP2C19*2 loss-of-function allele (OR: 2.9, p = 0.043), and age (OR: 0.94, p = 0.032) were variables significantly associated with optimal PD response (PRU <235) at 30 days. No correlations were found between PRU and lipid fractions. CONCLUSIONS: High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in our stable CAD patients with HTPR undergoing PCI (Atorvastatin and Clopidogrel HIgh DOse in stable patients with residual high platelet activity [ACHIDO]; NCT01335048).
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