title: Pharmacodynamic effects of adjunctive high dose atorvastatin on double dose clopidogrel in patients with high on-treatment platelet reactivity depending on diabetes mellitus status.
abstract: Diabetes mellitus (DM) is associated with impaired platelet response to clopidogrel. In patients with high on-treatment platelet reactivity (HTPR) while on standard-dose clopidogrel, high-dose atorvastatin enhances the pharmacodynamic (PD) effects of double-dose clopidogrel. It is unknown if similar effects are achieved in patients with DM. This study compare the PD effects of high-dose atorvastatin associated with double dose clopidogrel in HTPR patients with and without DM undergoing elective percutaneous coronary intervention (PCI). This is a post hoc analysis of a prospective randomized PD study that compared double-dose (150 mg) clopidogrel associated with high-dose (80 mg) atorvastatin to double-dose clopidogrel alone in statin naïve patients with HTPR undergoing elective PCI. In this analysis, patients were divided in two groups according to DM (n = 27) and non-DM (n = 49) status. Platelet reactivity was evaluated immediately before PCI and at 30 days using the VerifyNow P2Y12 assay. HTPR was defined as P2Y12 reaction units (PRU) ≥235. Administering high-dose atorvastatin in addition to high-dose clipodogrel, the 30 days absolute PRU changes (106 ± 75 vs 100 ± 42, p = 0.7) and optimal response rates (83 vs 84%; p = 0.9) were similar in DM and non-DM patients. The baseline variables significantly associated with 30-day optimal response to high-dose clopidogrel were: atorvastatin treatment (OR = 7.5 [95% CI 1.19-47]; p = 0.032) in DM patients; PRU values (OR = 0.9 [95% CI 0.95-0.99]; p = 0.031) and creatinine clearance (OR = 1.07 [95% CI 1.008-1.13]; p = 0.025) in non-DM patients. High-dose atorvastatin significantly improved the PD effects of double-dose clopidogrel in DM patients with HTPR undergoing elective PCI.
authors.affiliation: Division of Cardiology, Misericordia e Dolce Hospital, Via Cavour, 2 Prato, Italy, leoncini.mario@tiscali.it.
authors.forename: Mario
authors.initials: M
authors.lastname: Leoncini
authors.forename: Anna
authors.initials: A
authors.lastname: Toso
authors.forename: Mauro
authors.initials: M
authors.lastname: Maioli
authors.forename: Dominick J
authors.initials: DJ
authors.lastname: Angiolillo
authors.forename: Betti
authors.initials: B
authors.lastname: Giusti
authors.forename: Rossella
authors.initials: R
authors.lastname: Marcucci
authors.forename: Rosanna
authors.initials: R
authors.lastname: Abbate
authors.forename: Francesco
authors.initials: F
authors.lastname: Bellandi
mesh_terms: D000368:Aged; D000069059:Atorvastatin; D000077144:Clopidogrel; D003920:Diabetes Mellitus / Q000097:blood*; D005260:Female; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000493:pharmacokinetics; D008297:Male; D008875:Middle Aged; D062645:Percutaneous Coronary Intervention; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology; D011446:Prospective Studies; D011758:Pyrroles / Q000008:administration & dosage / Q000493:pharmacokinetics; D013927:Thrombosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics
chemical_list: D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D010975:Platelet Aggregation Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin; D000077144:Clopidogrel; D013988:Ticlopidine