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Platelet hyperactivity after statin treatment discontinuation

Journal: Thrombosis and Haemostasis
ISSN: 0340-6245
DOI: http://dx.doi.org/10.1160/TH03-02-0111
Issue: 2003: 90/3 (Sept) pp. 367-556
Pages: 476-482

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 as by non-lipid related actions. Among them, the modulation of platelet activity could play a relevant role in vascular protection. Furthermore withdrawal of statins has been associated with increased cardiovascular event rate. The aim of our study was to evaluate platelet activity after cerivastatin discontinuation in eighteen subjects that did not accept other drugs and in sixteen subjects continuing treatment with simvastatin. Fourteen subjects at the end of the discontinuation period decided to receive other drugs (simvastatin) and they were evaluted six weeks later. We measured complete lipid profile by the chromogenic method (LDL-C was calculated); oxidized-LDL (ox-LDL; ELISA), platelet P-selectin (P-sel) expression (flow cytometry detection), platelet aggregation (% change of trans-mitted light), intracellular citrullin production (iCit; HPLC) as an indicator of intracellular NO synthase activity at baseline and 7, 14, 28, 60 days after statin discontinuation. P-sel expres-sion and 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 aggregation at 28 days (r= 0.30, p< 0.05). Subjects continuing statin treat-ment had no significant changes of P-sel at 28 (p= 0.221) and 60 days (p=0.238). Subjects treated with simvastatin after 60 days of diet showed a significant reduction of P-sel and plate-let aggregation after six weeks of treatment (p< 0.01). Our data suggest a platelet hyperactivation state in the second week after statin discontinuation which is partially related to raised LDL-C. Such a finding could participate in the increased cardiovascular event rate after statin discontinuation.

DOI

http://dx.doi.org/10.1160/TH03-02-0111

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