Pharmacodynamic effects of atorvastatin versus rosuvastatin in coronary artery disease patients with normal platelet reactivity while on dual antiplatelet therapy--the PEARL randomized cross-over study.
High platelet reactivity during co-administration of clopidogrel and a CYP3A4-metabolized statin (i.e. atorvastatin) can be lowered by switching to a non-CYP3A4-metabolized statin (i.e rosuvastatin). Aim of this study was to verify if atorvastatin and rosuvastatin have different pharmacodynamic effects also when platelet reactivity while on dual antiplatelet therapy (DAPT) is normal at baseline. A total of 122 stable coronary artery disease patients receiving DAPT (clopidogrel 75 mg plus aspirin 100mg) who had evidence of normal platelet reactivity after a 1-week statin wash-out entered the trial. Patients were randomly assigned to atorvastatin (40 mg day, n=61) or rosuvastatin (20mg day, n=61) for 30 days. After another 1-week wash-out to avoid any carryover effect, cross-over was performed, and patients were switched to the other drug which was continued for 30 days. Platelet reactivity (expressed as P2Y(12) reaction units (PRU) by the VerifyNow assay [Accumetrics, San Diego, California]) was measured after 1-week statin wash-out and at the end of each treatment period. High platelet reactivity was defined as a PRU value >235. After 30-day atorvastatin, platelet reactivity did not significantly change as compared with pre-treatment evaluation (119 ± 66 vs. 136 ± 59 PRU, NS), with 2 patients only showing a PRU>235. Similarly, after 30-day rosuvastatin, platelet reactivity was unchanged vs. baseline (135 ± 46 vs. 128 ± 62 PRU, NS), with PRU>235 occurring in 3 patients. Atorvastatin does not negatively affect DAPT as compared with rosuvastatin when is given to stable coronary artery disease patients with normal platelet reactivity while in statin wash-out (ClinicalTrials.gov Identifier: NCT01567774).
Department "Attilio Reale", Sapienza University, Rome, Italy. Electronic address: f.pelliccia@mclink.it.
Francesco
F
Pelliccia
Medical Science Departement, IRCCS San Raffaele Pisana, Rome, Italy.
Giuseppe
G
Rosano
Medical Science Departement, IRCCS San Raffaele Pisana, Rome, Italy.
Giuseppe
G
Marazzi
Medical Science Departement, IRCCS San Raffaele Pisana, Rome, Italy; Laboratory of Vascular Physiology, IRCCS San Raffaele, London, UK.
Cristiana
C
Vitale
Medical Science Departement, IRCCS San Raffaele Pisana, Rome, Italy.
Ilaria
I
Spoletini
Department of Internal Medicine, University of Pisa, Pisa, Italy.
Ferdinando
F
Franzoni
Anthea Hospital, GVM Care & Research, ES Health Science Foundation, Bari, Italy.
Giuseppe
G
Speziale
Department "Attilio Reale", Sapienza University, Rome, Italy.
Marina
M
Polacco
Department "Attilio Reale", Sapienza University, Rome, Italy.
Cesare
C
Greco
Department "Attilio Reale", Sapienza University, Rome, Italy; Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy.
Carlo
C
Gaudio
D000069059:Atorvastatin; D001792:Blood Platelets / Q000187:drug effects* / Q000502:physiology*; D008078:Cholesterol, LDL / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy* / Q000378:metabolism*; D018592:Cross-Over Studies; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism; D005260:Female; D005464:Fluorobenzenes / Q000494:pharmacology* / Q000627:therapeutic use; D006538:Heptanoic Acids / Q000494:pharmacology* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011743:Pyrimidines / Q000494:pharmacology* / Q000627:therapeutic use; D011758:Pyrroles / Q000494:pharmacology* / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology* / Q000627:therapeutic use
D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D006538:Heptanoic Acids; D011743:Pyrimidines; D011758:Pyrroles; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D000069059:Atorvastatin; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human
Clopidogrel; Coronary artery disease; Percutaneous coronary intervention; Platelet reactivity