Key result
High-dose atorvastatin reduces platelet P-selectin expression vs ezetimibe-statin combination despite similar LDL-C lowering.
Why the study?
Does 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin reduce platelet activation markers, platelet aggregation, and plasma chemokine levels as effectively as 40 mg/day of atorvastatin alone in patients with coronary artery disease?
RCT (n=56)
Randomly assigned
Does 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin reduce platelet activation markers, platelet aggregation, and plasma chemokine levels as effectively as 40 mg/day of atorvastatin alone in patients with coronary artery disease?
In patients with coronary artery disease, higher-dose atorvastatin (40 mg/day) reduces platelet reactivity and proinflammatory chemokines more than ezetimibe plus low-dose atorvastatin (10 mg/day each), despite achieving similar LDL-C reductions.
Answers are grounded in this paper and cite their sources.
Higher-dose statin may be needed for optimal platelet inhibition in CAD; extends evidence that pleiotropic effects exceed LDL-C reduction alone.
Objectives We sought to test the platelet inhibitory and anti-inflammatory effects of a higher statin dosage compared with combined treatment with ezetimibe plus a low statin dose. Background Reducing the level of low-density lipoprotein cholesterol (LDL-C) with statins induces important pleiotropic effects such as platelet inhibition. An insufficient LDL-C reduction often is treated with ezetimibe, an intestinal cholesterol absorption inhibitor, in combination with a low statin dose. It is not known whether this combination therapy has the same pleiotropic effects as a statin monotherapy. Methods Fifty-six patients with coronary artery disease were assigned randomly to receive either 40 mg/day of atorvastatin or 10 mg/day of ezetimibe plus 10 mg/day of atorvastatin for 4 weeks. The levels of LDL-C, platelet activation markers after stimulation, platelet aggregation, and plasma chemokine levels (i.e., regulated on activation normally T-cell expressed and secreted [RANTES]) were measured before and after changing lipid-lowering medication. Results Platelet activation markers (P-selectin) after stimulation (adenosine diphosphate) were reduced by 40 mg/day of atorvastatin (-5.2 +/- 1.6 arbitrary units) but not by ezetimibe plus low-dose atorvastatin (2.1 +/- 1.8 arbitrary units; p < 0.005) despite a similar reduction of LDL-C (atorvastatin -1.01 +/- 0.18 mmol/l vs. ezetimibe plus atorvastatin -1.36 +/- 0.22 mmol/l, p = NS). Thrombin receptor-activating peptide-induced platelet aggregation as well as plasma RANTES levels were reduced by 40 mg/day of atorvastatin but not by ezetimibe plus low-dose atorvastatin. Conclusions Platelet reactivity and a proinflammatory chemokine were reduced more by the higher atorvastatin dose than by ezetimibe plus low-dose atorvastatin. In patients with coronary artery disease, it might be important to combine ezetimibe with higher statin dosages to benefit from cholesterol-independent pleiotropic effects.
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Piorkowski et al. (2007) conducted an RCT in Coronary artery disease (n=56). Ezetimibe plus low-dose atorvastatin vs. 40 mg/day atorvastatin alone was evaluated on Change in ADP-stimulated platelet P-selectin expression (arbitrary units) (p=< 0.005). Higher-dose atorvastatin reduced platelet P-selectin expression, whereas ezetimibe plus low-dose atorvastatin did not despite similar LDL-C reduction.
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