We investigated whether, in primary prevention patients with
metabolic syndrome,
statins affect the platelet
protease-activated receptor-1 (PAR-1)
thrombin receptor by performing serial measurements of its activity and the
antigen expression level by flow cytometry before and during treatment. Recent data from randomized trials of
statins are compatible with the possibility of clinically relevant pleiotropic effects. The use of
statins is associated with a reduced
thrombosis burden and diminished platelet activity, as shown in animal models and in vitro studies. Seventy patients with the
metabolic syndrome who were not taking
antiplatelet agents were assigned consecutively at starting doses at the discretion of the responsible clinician to 1 of 6
statins (
atorvastatin,
fluvastatin,
lovastatin,
pravastatin,
rosuvastatin, or
simvastatin) or to a no-
statin group for 6 weeks. Platelet expression of intact (SPAN12 antibody) and cleaved (WEDE15) PAR-1
thrombin receptors were assessed by flow cytometry at baseline and at weeks 4 and 6 of treatment. At baseline, no difference was found in receptor expression. However, after 4 weeks of treatment, all
statins had significantly inhibited (46% to 55%) the activated
epitope of PAR-1 expression. After 6 weeks, inhibition remained, despite a slight rebound (22% to 37%). Also, a delayed pattern of inhibition of the intact
PAR-1 receptor epitope was found. In conclusion, all
statins inhibited the activity and
antigen level of the platelet PAR-1
thrombin receptor, which has a major role in regulating platelet activity and
thrombin formation. These observational data offer a plausible mechanism for the recently demonstrated pleiotropic effects of
statins that may contribute to early clinical benefit.