Platelet hyperactivity after statin treatment discontinuation
Luca Puccetti, Anna Laura Pasqui, Marcello Pastorelli, Giovanni Bova, Michela Di Renzo, Alessandro Leo, Michela Cercignani, Alberto Palazzuoli, Alberto Auteri, Fulvio Bruni
Department of Clinical Medicine and Immunological Sciences. Internal Medicine Division. Center for Metabolic Diseases and Atherosclerosis. University of Siena, Siena, Italy
Summary Hydroxymethyl-glutaryl-CoA-reductase inhibitors (statins)reduce cardiovascular events by cholesterol lowering as well asby non-lipid related actions. Among them, the modulation ofplatelet activity could play a relevant role in vascular protection.Furthermore withdrawal of statins has been associated withincreased cardiovascular event rate. The aim of our study wasto evaluate platelet activity after cerivastatin discontinuation ineighteen subjects that did not accept other drugs and in sixteensubjects continuing treatment with simvastatin. Fourteensubjects at the end of the discontinuation period decided toreceive other drugs (simvastatin) and they were evaluted sixweeks later. We measured complete lipid profile by thechromogenic method (LDL-C was calculated); oxidized-LDL(ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flowcytometry detection), platelet aggregation (% change of trans-mittedlight), intracellular citrullin production (iCit; HPLC) asan indicator of intracellular NO synthase activity at baselineand 7, 14, 28, 60 days after statin discontinuation. P-sel expres-sionand platelet aggregation were increased at 14 days(p< 0.001 and p< 0.05) in association with raised ox-LDL(r= 0.30, p< 0.05) and decreased iCit (r= 0.53, p< 0.01).Increased LDL-C was related to P-sel and platelet aggregationat 28 days (r= 0.30, p< 0.05). Subjects continuing statin treat-menthad no significant changes of P-sel at 28 (p= 0.221) and60 days (p=0.238). Subjects treated with simvastatin after60 days of diet showed a significant reduction of P-sel and plate-letaggregation after six weeks of treatment (p< 0.01).Our data suggest a platelet hyperactivation state in the secondweek after statin discontinuation which is partially related toraised LDL-C. Such a finding could participate in the increasedcardiovascular event rate after statin discontinuation.