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      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.

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          Abstract

          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).

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          Author and article information

          Journal
          Eur. J. Pharmacol.
          European journal of pharmacology
          Elsevier BV
          1879-0712
          0014-2999
          Feb 15 2014
          : 725
          Affiliations
          [1 ] Department "Attilio Reale", Sapienza University, Rome, Italy. Electronic address: f.pelliccia@mclink.it.
          [2 ] Medical Science Departement, IRCCS San Raffaele Pisana, Rome, Italy.
          [3 ] Medical Science Departement, IRCCS San Raffaele Pisana, Rome, Italy; Laboratory of Vascular Physiology, IRCCS San Raffaele, London, UK.
          [4 ] Department of Internal Medicine, University of Pisa, Pisa, Italy.
          [5 ] Anthea Hospital, GVM Care & Research, ES Health Science Foundation, Bari, Italy.
          [6 ] Department "Attilio Reale", Sapienza University, Rome, Italy.
          [7 ] Department "Attilio Reale", Sapienza University, Rome, Italy; Eleonora Lorillard Spencer Cenci Foundation, Rome, Italy.
          Article
          S0014-2999(14)00007-7
          10.1016/j.ejphar.2014.01.006
          24444439

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