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.
abstract: OBJECTIVE
  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).
authors: Division of Cardiology, Misericordia e Dolce Hospital, Prato, Italy. leoncini.mario@tiscali.it
authors: Mario
authors: M
authors: Leoncini
authors: Anna
authors: A
authors: Toso
authors: Mauro
authors: M
authors: Maioli
authors: Dominick J
authors: DJ
authors: Angiolillo
authors: Betti
authors: B
authors: Giusti
authors: Rossella
authors: R
authors: Marcucci
authors: Rosanna
authors: R
authors: Abbate
authors: Francesco
authors: F
authors: Bellandi
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D016009:Chi-Square Distribution; D000077144:Clopidogrel; D003324:Coronary Artery Disease / Q000097:blood / Q000628:therapy*; D065731:Cytochrome P-450 CYP2C19; D004347:Drug Interactions; D004351:Drug Resistance; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D007558:Italy; D008297:Male; D008875:Middle Aged; D016017:Odds Ratio; D062645:Percutaneous Coronary Intervention / Q000009:adverse effects; D010597:Pharmacogenetics; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D010979:Platelet Function Tests; D011446:Prospective Studies; D058921:Purinergic P2Y Receptor Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D011758:Pyrroles / Q000008:administration & dosage* / Q000009:adverse effects; D058925:Receptors, Purinergic P2Y12 / Q000097:blood / Q000187:drug effects; D018570:Risk Assessment; D012307:Risk Factors; D013988:Ticlopidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058921:Purinergic P2Y Receptor Antagonists; D011758:Pyrroles; D058925:Receptors, Purinergic P2Y12; D000069059:Atorvastatin; D000077144:Clopidogrel; D001189:Aryl Hydrocarbon Hydroxylases; C045793:CYP2C19 protein, human; D065731:Cytochrome P-450 CYP2C19; D013988:Ticlopidine