Update hypercholesterolemie & ezetimibe

Literatuur - Phan BA, Dayspring TD, Toth PP - Vasc Health Risk Manag. 2012;8:415-27

Ezetimibe therapy: mechanism of action and clinical update.

Phan BA, Dayspring TD, Toth PP.
Vasc Health Risk Manag. 2012;8:415-27.

Achtergrond

Er is een duidelijk verband tussen verhoogde serum cholesterolwaarden en cardiovasculair risico [1,2]. Behandeling met statines verlaagt effectief LDL-C-waarden en vermindert ernstige cardiovasculaire gebeurtenissen [3-7]. Meer agressieve verlaging van de LDL-C kan het cardiovasculaire voordeel verhogen [8-10], vooral in hoog-risico patiënten met meerdere risicofactoren [11]. Om optimale LDL-C waarden te bereiken, is alleen statinetherapie wellicht niet voldoende. Bij deze patiënten wordt combinatie met andere cholesterolverlagende middelen aanbevolen, zoals de cholesterolabsorptie remmer ezetimibe. Het werkingsmechanisme, effecten op lipiden, en de veiligheid van behandeling met ezetimibe behandeling worden beschreven, evenals studies die van invloed kunnen zijn op het gebruik in de klinische praktijk.

Samenvatting

Ezetimibe remt intestinale absorptie van cholesterol door het selectief blokkeren van het Niemann-Pick C1-achtig eiwit (NPC1L1) in de jejunale brush border, een integraal onderdeel van de opname van intestinale lumen micellen in de enterocyt [12-15]. Het is, hetzij als monotherapie of in combinatie met statines, effectief in het verlagen van cholesterol in verschillende populaties, zoals insulineresistentie, FH en sitosterolemie.

Zowel in de SANDS als de VYCTOR studie werd regressie van atherosclerose gerapporteerd [16-18]. De klinische werkzaamheid van behandeling met ezetimibe werd geëvalueerd in de SEAS studie [19] en in de SHARP studie [20], beide met ezetimibe plus simvastatine (figuur 1).

De ENHANCE [21] en ARBITER-6 studie [22] rapporteerden echter negatieve uitkomsten, hoewel beide studies methodologisch beperkt waren in hun vermogen om het voordeel van ezetimibe te evalueren. Daarom wordt met spanning uitgekeken naar de komende resultaten van de IMPROVE-IT-studie [23]. Deze resultaten kunnen het gebruik van ezetimibe in zeer hoog risico CHD populaties beter sturen.

Conclusie

Vooralsnog is ezetimibe een waardevolle aanvulling op statinetherapie bij de behandeling van hypercholesterolemie. Komende studieresultaten worden verwacht om het effect in de klinische praktijk beter te beoordelen.

Figuur 1.

Proportionele reductie van grote ischemische complicaties per gemiddelde daling van de LDL-C (mmol / L) in de Simvastatine en Ezetimibe in Aortastenose (SEAS) trial (tertielen 1, 2, en 3 voor de ernst van de aortaklepstenose) ten opzichte van 14 gerandomiseerde trials in de Cholesterol Treatment Trialists meta-analyse.
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Abstract

The lowering of low-density lipoprotein cholesterol (LDL-C) is the primary target of therapy in the primary and secondary prevention of cardiovascular events. Although statin therapy is the mainstay for LDL-C lowering, a significant percentage of patients prescribed these agents either do not achieve targets with statin therapy alone or have partial or complete intolerance to them. For such patients, the use of adjuvant therapy capable of providing incremental LDL-C reduction is advised. One such agent is ezetimibe, a cholesterol absorption inhibitor that targets uptake at the jejunal enterocyte brush border. Its primary target of action is the cholesterol transport protein Nieman Pick C1 like 1 protein. Ezetimibe is an effective LDL-C lowering agent and is safe and well tolerated. In response to significant controversy surrounding the use and therapeutic effectiveness of this drug, we provide an update on the biochemical mechanism of action for ezetimibe, its safety and efficacy, as well as the results of recent randomized studies that support its use in a variety of clinical scenarios.