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L'eprotirome potenzia l'effetto delle statine sulle lipoproteine aterogene

L'eprotirome è un analogo degli ormoni tiroidei che è solo minimamente captato nei tessuti extraepatici. La sua azione si esercita pertanto principalmente sul fegato dove induce una sorta di "ipertiroidismo epatico", responsabile dell'azione metabolica del farmaco, senza provocare gli effetti sistemici tipici dell'ipertiroidismo. In questo studio dove l'eprotirome è stato somministrato a dosi di 25, 50 o 100 mcg, non si sono osservate modificazioni del peso corporeo, della frequenza cardiaca, della pressione arteriosa, non si sono verificati disturbi del ritmo cardiaco o alterazioni elettrocardiografiche. Si è invece osservata una riduzione dose dipendente dei livelli di tiroxina libera (dal 12% al 21%), ma nel complesso i valori della tiroxina e del TSH sono sempre rimasti nei limiti di riferimento. L'aggiunta dell'eprotirome alla terapia con statina ha determinato una diminuzione dose dipendente del 22%-32%, del colesterolo LDL, del 16%-33% dei trigliceridi e del 27-43% della Lp(a).

Use of the thyroid hormone analogue eprotirome in statin-treated dyslipidemia.

Ladenson PW, Kristensen JD, Ridgway EC, Olsson AG, Carlsson B, Klein I, Baxter JD, Angelin B.

N Engl J Med 2010;362:906-916

BACKGROUND: Dyslipidemia increases the risk of atherosclerotic cardiovascular disease and is incompletely reversed by statin therapy alone in many patients. Thyroid hormone lowers levels of serum low-density lipoprotein (LDL) cholesterol and has other potentially favorable actions on lipoprotein metabolism. Consequently, thyromimetic drugs hold promise as lipid-lowering agents if adverse effects can be avoided. METHODS: We performed a randomized, placebo-controlled, double-blind, multicenter trial to assess the safety and efficacy of the thyromimetic compound eprotirome (KB2115) in lowering the level of serum LDL cholesterol in patients with hypercholesterolemia who were already receiving simvastatin or atorvastatin. In addition to statin treatment, patients received either eprotirome (at a dose of 25, 50, or 100 microg per day) or placebo. Secondary outcomes were changes in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Patients were monitored for potential adverse thyromimetic effects on the heart, bone, and pituitary. RESULTS: The addition of placebo or eprotirome at a dose of 25, 50, or 100 microg daily to statin treatment for 12 weeks reduced the mean level of serum LDL cholesterol from 141 mg per deciliter (3.6 mmol per liter) to 127, 113, 99, and 94 mg per deciliter (3.3, 2.9, 2.6, and 2.4 mmol per liter), respectively, (mean reduction from baseline, 7%, 22%, 28%, and 32%). Similar reductions were seen in levels of serum apolipoprotein B, triglycerides, and Lp(a) lipoprotein. Eprotirome therapy was not associated with adverse effects on the heart or bone. No change in levels of serum thyrotropin or triiodothyronine was detected, although the thyroxine level decreased in patients receiving eprotirome. CONCLUSIONS: In this 12-week trial, the thyroid hormone analogue eprotirome was associated with decreases in levels of atherogenic lipoproteins in patients receiving treatment with statins. (ClinicalTrials.gov number, NCT00593047.)

N Engl J Med 2010;362:906-916