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Un anno di terapia con Evolocumab

Sono oltre 900 i pazienti con colesterolo LDL maggiore di 75 mg/dL e trigliceridi minori di 400 mg/dL che sono stati trattati per un anno con 420 mg di evolocumab ogni 4 settimane. Di essi, 111 erano già solo in terapia dietetica, 383 assumevano atorvastatina 10 mg, 218 atorvastatina 80 mg e 189 atorvastatina 80 mg+ezetimibe 10 mg e la terapia già in atto è stata mantenuta invariata per tutto il periodo di studio. I risultati sono stati quelli attesi sulla base degli studi preliminari e cioè una riduzione media del colesterolo LDL di circa il 56% con un massimo del 62% in coloro che erano in terapia dietetica ed un minimo del 49% nel gruppo più resistente in terapia con l'associazione atorvastatina 80 ed ezetimibe 10. Il colesterolo LDL medio alla fine dell'anno di trattamento variava da un massimo di 64 mg/dL nel gruppo atorvastatina+ezetimibe ad un minimo di 45 mg/dL nel gruppo atorvastatina 10 mg. Per quanto riguarda la tolleranza, i dati sono buoni ed in linea con quanto già segnalato negli studi di più breve durata. Rinofaringite, infezioni del tratto respiratorio superiore, sintomi similinfluenzali e mal di schiena sono gli effetti collaterali più frequentemente riportati. Da segnalare anche mialgia ed elevazione del CPK nell'1,2% e nel 3,0% dei pazienti.

A 52-week placebo-controlled trial of evolocumab in hyperlipidemia.

Blom DJ, Hala T, Bolognese M, Lillestol MJ, Toth PD, Burgess L, Ceska R, Roth E, Koren MJ, Ballantyne CM, Monsalvo ML, Tsirtsonis K, Kim JB, Scott R, Wasserman SM, Stein EA; DESCARTES Investigators

New Engl J Med 2014;370:1809-1819

BACKGROUND: Evolocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), significantly reduced low-density lipoprotein (LDL) cholesterol levels in phase 2 studies. We conducted a phase 3 trial to evaluate the safety and efficacy of 52 weeks of treatment with evolocumab.
METHODS: We stratified patients with hyperlipidemia according to the risk categories outlined by the Adult Treatment Panel III of the National Cholesterol Education Program. On the basis of this classification, patients were started on background lipid-lowering therapy with diet alone or diet plus atorvastatin at a dose of 10 mg daily, atorvastatin at a dose of 80 mg daily, or atorvastatin at a dose of 80 mg daily plus ezetimibe at a dose of 10 mg daily, for a run-in period of 4 to 12 weeks. Patients with an LDL cholesterol level of 75 mg per deciliter (1.9 mmol per liter) or higher were then randomly assigned in a 2:1 ratio to receive either evolocumab (420 mg) or placebo every 4 weeks. The primary end point was the percent change from baseline in LDL cholesterol, as measured by means of ultracentrifugation, at week 52.
RESULTS: Among the 901 patients included in the primary analysis, the overall least-squares mean (±SE) reduction in LDL cholesterol from baseline in the evolocumab group, taking into account the change in the placebo group, was 57.0±2.1% (P<0.001). The mean reduction was 55.7±4.2% among patients who underwent background therapy with diet alone, 61.6±2.6% among those who received 10 mg of atorvastatin, 56.8±5.3% among those who received 80 mg of atorvastatin, and 48.5±5.2% among those who received a combination of 80 mg of atorvastatin and 10 mg of ezetimibe (P<0.001 for all comparisons). Evolocumab treatment also significantly reduced levels of apolipoprotein B, non-high-density lipoprotein cholesterol, lipoprotein(a), and triglycerides. The most common adverse events were nasopharyngitis, upper respiratory tract infection, influenza, and back pain.
CONCLUSIONS: At 52 weeks, evolocumab added to diet alone, to low-dose atorvastatin, or to high-dose atorvastatin with or without ezetimibe significantly reduced LDL cholesterol levels in patients with a range of cardiovascular risks.

New Engl J Med 2014;370:1809-1819