Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial.

Détails

ID Serval
serval:BIB_FB26EAE36F4F
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Effect of evolocumab or ezetimibe added to moderate- or high-intensity statin therapy on LDL-C lowering in patients with hypercholesterolemia: the LAPLACE-2 randomized clinical trial.
Périodique
Jama
Auteur(s)
Robinson J.G., Nedergaard B.S., Rogers W.J., Fialkow J., Neutel J.M., Ramstad D., Somaratne R., Legg J.C., Nelson P., Scott R., Wasserman S.M., Weiss R.
Collaborateur(s)
LAPLACE-2 Investigators
Contributeur(s)
Hamilton A., Lehman R., Proietto J., Simons L., Bous JP., Cornelli K., De Munck L., Vantroyen , Vermeersch L., Vileyn G., Akhras R., Cha J., Chehayeb R., Chilvers M., Collette R., Dowell A., Dzongowski P., Gupta A., Halperin F., Hart R., Heaton K., Henein S., Kanani S., Kornder J., Lamy A., OMahony M., Pandey A., Sabe-Affaki G., St Maurice F., Adamkova V., Cermak O., Ceska R., Frana P., Hala T., Kellnerova I., Machkova M., Petrzelkova J., Pojsl S., Stankova V., Vaclavik J., Zemanek J., Krogsaa A., Nedergaard BS., Wermuth S., Clavel S., Cohen AA., Davy JM., Joubert M., Mansourati J., Probst V., Verges B., Degtyareva E., Förster A., Horacek T., Kasperk C., Kohler E., Laufs U., Meissner G., Schenkenberger I., Stoessel J., Trenk D., Winkler K., Lau EM., Yeung CY., Bajnok L., Bod E., Harcsa E., Lippai J., Mohacsi A., Palinkas A., Poor F., Szakal I., Sziegl Z., Borghi C., Bucci M., Cattin L., Iannuzzi A., Miccoli R., Passaro A., Pintus P., Pirro M., Sirtori C., Zambon S., De Graaf J., Donders S., Imholz B., Klessens-Godfroy F., Kooy A., Stroes E., Van Leendert R., Viergever P., Helder D., Vincent H., Barbarash O., Chumakova G., Demchenko E., Kotelnikov M., Litvin A., Lukyanov Y., Shvarts Y., Susekov A., Treshkur T., Yakhontova P., Gimilio JF., Gimeno EJ., Raya PM., Nuñez-Cortes JM., Prieto JM., Sala XP., Ros E., Borgencrantz B., Bosson P., Curiac D., Dahlén G., Delavaran C., Lindholm CJ., Burnier M., Eberli F., Gallino A., Mach F., Rickli H., Widmer F., Abdulhakim EE., Adler L., Blagden M., D'Costa R., Falk R., Fisher M., Hassanin H., Horvathova V., Kerrane J., Mackay J., McCormack T., McKinnon C., Oyesile B., Pavel-Knox I., Soran H., Thomas H., Abraham W., Aronoff S., Atassi K., Awasty V., Bailey K., Baron S., Bear R., Bertolet B., Bhagwat R., Coburn N., Connery L., Dauber I., Davis M., Diederich C., Eaton G., Fialkow J., Fishbein G., French W., Friedlander I., Fuchs-Ertman D., Ginsberg D., Hagan M., Hage-Korban E., Halpern S., Henderson D., Houser P., Ibrahim H., Jennings W., Kivitz A., Kozlowski L., Loh I., Malone M., McConnehey B., McCullum K., Miller M., Napoli M., Neutel J., Purdy D., Qureshi M., Ramstad D., Raoof T., Reichman A., Rich K., Robinson J., Rogers W., Salazar J., Shaoulian E., Stringer J., Tarleton G., Throne M., Webb C., Weiss R., Wiseman A.
ISSN
1538-3598 (Electronic)
ISSN-L
0098-7484
Statut éditorial
Publié
Date de publication
05/2014
Volume
311
Numéro
18
Pages
1870-1882
Langue
anglais
Notes
Publication types: Clinical Trial, Phase III ; Journal Article ; Multicenter Study ; Randomized Controlled Trial ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
IMPORTANCE: In phase 2 studies, evolocumab, a fully human monoclonal antibody to PCSK9, reduced LDL-C levels in patients receiving statin therapy.
OBJECTIVE: To evaluate the efficacy and tolerability of evolocumab when used in combination with a moderate- vs high-intensity statin.
DESIGN, SETTING, AND PATIENTS: Phase 3, 12-week, randomized, double-blind, placebo- and ezetimibe-controlled study conducted between January and December of 2013 in patients with primary hypercholesterolemia and mixed dyslipidemia at 198 sites in 17 countries.
INTERVENTIONS: Patients (n = 2067) were randomized to 1 of 24 treatment groups in 2 steps. Patients were initially randomized to a daily, moderate-intensity (atorvastatin [10 mg], simvastatin [40 mg], or rosuvastatin [5 mg]) or high-intensity (atorvastatin [80 mg], rosuvastatin [40 mg]) statin. After a 4-week lipid-stabilization period, patients (n = 1899) were randomized to compare evolocumab (140 mg every 2 weeks or 420 mg monthly) with placebo (every 2 weeks or monthly) or ezetimibe (10 mg or placebo daily; atorvastatin patients only) when added to statin therapies.
MAIN OUTCOMES AND MEASURES: Percent change from baseline in low-density lipoprotein cholesterol (LDL-C) level at the mean of weeks 10 and 12 and at week 12.
RESULTS: Evolocumab reduced LDL-C levels by 66% (95% CI, 58% to 73%) to 75% (95% CI, 65% to 84%) (every 2 weeks) and by 63% (95% CI, 54% to 71%) to 75% (95% CI, 67% to 83%) (monthly) vs placebo at the mean of weeks 10 and 12 in the moderate- and high-intensity statin-treated groups; the LDL-C reductions at week 12 were comparable. For moderate-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 115 to 124 mg/dL to an on-treatment mean of 39 to 49 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 123 to 126 mg/dL to an on-treatment mean of 43 to 48 mg/dL. For high-intensity statin groups, evolocumab every 2 weeks reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 35 to 38 mg/dL; monthly evolocumab reduced LDL-C from a baseline mean of 89 to 94 mg/dL to an on-treatment mean of 33 to 35 mg/dL. Adverse events were reported in 36%, 40%, and 39% of evolocumab-, ezetimibe-, and placebo-treated patients, respectively. The most common adverse events in evolocumab-treated patients were back pain, arthralgia, headache, muscle spasms, and pain in extremity (all <2%).
CONCLUSIONS AND RELEVANCE: In this 12-week trial conducted among patients with primary hypercholesterolemia and mixed dyslipidemia, evolocumab added to moderate- or high-intensity statin therapy resulted in additional LDL-C lowering. Further studies are needed to evaluate the longer-term clinical outcomes and safety of this approach for LDL-C lowering.
TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01763866.
Mots-clé
Aged, Antibodies, Monoclonal/therapeutic use, Anticholesteremic Agents/administration & dosage, Azetidines/therapeutic use, Double-Blind Method, Drug Therapy, Combination, Dyslipidemias/drug therapy, Female, Fluorobenzenes/administration & dosage, Heptanoic Acids/administration & dosage, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage, Hypercholesterolemia/drug therapy, Male, Middle Aged, Pyrimidines/administration & dosage, Pyrroles/administration & dosage, Simvastatin/administration & dosage, Sulfonamides/administration & dosage, Treatment Outcome
Pubmed
Création de la notice
03/12/2014 18:01
Dernière modification de la notice
03/03/2018 22:57
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