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.