SISANews

La combinazione simvastatina-ezetimibe migliora la funzione endoteliale

Il miglioramento della funzione endoteliale è uno degli effetti noti della terapia con statine, attribuibile con ogni probabilità alla ridotta produzione di isoprenoidi che aumenta la biodisponibilità di ossido nitrico. Non è chiaro se questo effetto sia o no indipendente dall'azione principale delle statine e cioè la riduzione del colesterolo LDL. Questo studio, condotto su pazienti con sindrome metabolica, dimostra che a parità di riduzione del colesterolo LDL, ottenuta con simvastatina 80 mg o con l'associazione simvastatina 10 mg + ezetimibe 10 mg, la funzione endoteliale, sia a digiuno, sia nel periodo postprandiale, quando essa è maggiormente compromessa, migliora in maniera del tutto simile. Il miglioramento della funzione endoteliale è dunque strettamente connesso alla riduzione del colesterolo LDL e indipendente dal tipo della terapia ipocolesterolemizzante.

High-dose statin monotherapy versus low-dose statin/ezetimibe combination on fasting and postprandial lipids and endothelial function in obese patients with the metabolic syndrome: The PANACEA study

Westerink J, Deanfield JE, Imholz BP, Spiering W, Basart DC, Coll B, Kastelein JJ, Visseren FL

Atherosclerosis 2013;227:118-124

BACKGROUND: Low-dose statin therapy in combination with ezetimibe, an inhibitor of intestinal cholesterol absorption, lowers plasma LDL-cholesterol levels to a similar degree as high-dose statin monotherapy. This study assessed whether similar LDL-cholesterol lowering with simvastatin/ezetimibe combination therapy improves fasting and postprandial arterial endothelial function compared to high-dose statin therapy alone.
METHODS: Multicenter, double-blind, crossover trial in 100 abdominally obese patients with the metabolic syndrome, randomized to 6 weeks' treatment with simvastatin 80 mg or simvastatin/ezetimibe 10/10 mg. Flow mediated dilatation (FMD) and peripheral arterial tonometry (EndoPAT) as well as plasma lipids were measured in the fasting state and after an oral lipid load at baseline and after both treatments.
RESULTS: Fasting LDL-cholesterol levels (3.57 mmol/L at baseline) were reduced to 1.79 mmol/L following treatment with simvastatin 80 mg and 1.81 mmol/L with simvastatin/ezetimibe 10/10 mg, respectively. Plasma lipids were similar at 4 h after an oral lipid load following both treatments for 6 weeks. Fasting endothelial function was also similar with both treatments when assessed by FMD (adjusted mean ± SE: 4.35 ± 0.19 vs. 4.43 ± 0.18; P = 0.777) and EndoPAT (2.12 ± 0.05 vs 2.20 ± 0.05; P = 0.304). After an oral fat load, changes in endothelial function were also comparable for both treatments as assessed by FMD (-0.34 ± 0.21 vs. -0.43 ± 0.20; P = 0.766) and EndoPAT (0.00 ± 0.07 vs. -0.04 ± 0.08; P = 0.712).
CONCLUSION: Treatment with simvastatin/ezetimibe 10/10 mg induced no difference in endothelial function in the fasting and postprandial state compared to simvastatin 80 mg while attaining similar LDL-c levels in obese patients with metabolic syndrome.

Atherosclerosis 2013;227:118-124