CLINICAL RESEARCH
Treatment With Ezetimibe Plus Low-Dose Atorvastatin Compared With Higher-Dose Atorvastatin AloneIs Sufficient Cholesterol-Lowering Enough to Inhibit Platelets?
Michael Piorkowski, MD*,
Sabine Fischer, MD*,
Caroline Stellbaum, MD*,
Markus Jaster, MD*,
Peter Martus, PhD ,
Andreas J. Morguet, MD*,
Heinz-Peter Schultheiss, MD* and
Ursula Rauch, MD*,*
* Department of Internal Medicine/Cardiology
Institute for Biostatistics and Clinical Epidemiology, Campus Benjamin Franklin, Charité Universitätsmedizin Berlin, Berlin, Germany
Manuscript received April 19, 2006;
revised manuscript received October 20, 2006,
accepted October 23, 2006.
* Reprint requests and correspondence: Dr. Ursula Rauch, Charité Universitätsmedizin Berlin, Campus Benjamin Franklin, Department of Internal Medicine/Cardiology, Hindenburgdamm 30, 12200 Berlin, Germany (Email: ursula.rauch{at}charite.de).
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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Abbreviations and Acronyms
| | ADP = adenosine diphosphate | | AU = arbitrary units | | CAD = coronary artery disease | | HDL-C = high-density lipoprotein cholesterol | | LDL-C = low-density lipoprotein cholesterol | | MA = maximum aggregation | | MFI = median immunofluorescence intensity | | RANTES = regulated on activation normally T-cell expressed and secreted | | SL = maximum slope of aggregation | | TG = triglycerides | | TRAP = thrombin receptor-activating peptide |
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