TY - JOUR
T1 - Efficacy and Safety of Alirocumab in Reducing Lipids and Cardiovascular Events
AU - Robinson, Jennifer G.
AU - Farnier, Michel
AU - Krempf, Michel
AU - Bergeron, Jean
AU - Luc, Gérald
AU - Averna, Maurizio
AU - Stroes, Erik S.
AU - Langslet, Gisle
AU - Raal, Frederick J.
AU - El Shahawy, Mahfouz
AU - Koren, Michael J.
AU - Lepor, Norman E.
AU - Lorenzato, Christelle
AU - Pordy, Robert
AU - Chaudhari, Umesh
AU - Kastelein, John J. P.
AU - AUTHOR GROUP
AU - Caccavo, Alberto
AU - Codutti, Oscar
AU - Gelersztein, Elisabeth
AU - Vico, Marisa
AU - Zaidman, Cesar
AU - Majul, Claudio
AU - Balthazar, Yohan
AU - Capiau, Luc
AU - Vrolix, Mathias
AU - Vermeersch, Paul
AU - Gotchev, Dobromir
AU - Todorov, Georgi
AU - Tumbev, Haralin
AU - Tzekova, Maria
AU - Gronkova, Naydenka
AU - Dimov, Bojidar
AU - Nikolaeva, Antonoaneta
AU - Devedzhiev, Tsvetan
AU - Mincheva, Valentina
AU - D'Ignazio, Giuseppe
AU - Dzongowski, Peter
AU - Elliott, Thomas
AU - Hart, Randy
AU - Hoag, Gordon
AU - Martinho, Valdemar
AU - O'Mahony, Michael
AU - Tellier, Guy
AU - Pandey, Shekhar
AU - Heaton, Kenneth
AU - Constance, Christian
AU - Phaneuf, Denis-Carl
AU - Shu, Daniel
AU - Narvaez, Nancy Cardenas
AU - Cañon, Claudia Olivares
PY - 2015
Y1 - 2015
N2 - BACKGROUND Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. METHODS We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2: 1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. RESULTS At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P <0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P = 0.02). CONCLUSIONS Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab
AB - BACKGROUND Alirocumab, a monoclonal antibody that inhibits proprotein convertase subtilisin-kexin type 9 (PCSK9), has been shown to reduce low-density lipoprotein (LDL) cholesterol levels in patients who are receiving statin therapy. Larger and longer-term studies are needed to establish safety and efficacy. METHODS We conducted a randomized trial involving 2341 patients at high risk for cardiovascular events who had LDL cholesterol levels of 70 mg per deciliter (1.8 mmol per liter) or more and were receiving treatment with statins at the maximum tolerated dose (the highest dose associated with an acceptable side-effect profile), with or without other lipid-lowering therapy. Patients were randomly assigned in a 2: 1 ratio to receive alirocumab (150 mg) or placebo as a 1-ml subcutaneous injection every 2 weeks for 78 weeks. The primary efficacy end point was the percentage change in calculated LDL cholesterol level from baseline to week 24. RESULTS At week 24, the difference between the alirocumab and placebo groups in the mean percentage change from baseline in calculated LDL cholesterol level was -62 percentage points (P <0.001); the treatment effect remained consistent over a period of 78 weeks. The alirocumab group, as compared with the placebo group, had higher rates of injection-site reactions (5.9% vs. 4.2%), myalgia (5.4% vs. 2.9%), neurocognitive events (1.2% vs. 0.5%), and ophthalmologic events (2.9% vs. 1.9%). In a post hoc analysis, the rate of major adverse cardiovascular events (death from coronary heart disease, nonfatal myocardial infarction, fatal or nonfatal ischemic stroke, or unstable angina requiring hospitalization) was lower with alirocumab than with placebo (1.7% vs. 3.3%; hazard ratio, 0.52; 95% confidence interval, 0.31 to 0.90; nominal P = 0.02). CONCLUSIONS Over a period of 78 weeks, alirocumab, when added to statin therapy at the maximum tolerated dose, significantly reduced LDL cholesterol levels. In a post hoc analysis, there was evidence of a reduction in the rate of cardiovascular events with alirocumab
U2 - https://doi.org/10.1056/NEJMoa1501031
DO - https://doi.org/10.1056/NEJMoa1501031
M3 - Article
C2 - 25773378
SN - 0028-4793
VL - 372
SP - 1489
EP - 1499
JO - New England journal of medicine
JF - New England journal of medicine
IS - 16
ER -