Efficacy and safety of alirocumab in reducing lipids and cardiovascular events.
By Jennifer G. Robinson, M. Farnier, M. Krempf, J. Bergeron, G. Luc, M. Averna, E. Stroes, G. Langslet, F. Raal, M. El Shahawy and 6 more. New England Journal of Medicine, 2015
2,054 citations recorded by the source corpus.
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. (Funded by Sanofi and Regeneron Pharmaceuticals; ODYSSEY LONG TERM ClinicalTrials.gov number, NCT01507831.).
Subfields: Pulmonary and Respiratory Medicine, Surgery
View Paper: https://www.semanticscholar.org/paper/942bcfdc93b04ccb90a2d3e1df4c7950a45e92c2
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Citations in the corpus
- 2016 ESC/EAS Guidelines for the Management of Dyslipidaemias. (2016, background): “); preliminary data from phase 3 trials suggest a reduction of CV events in line with the LDL-C reduction achieved.(115,116) A recent meta-analysis confirmed these findings.”
- Metabolic syndrome update. (2016, background): “[88] Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al.”
- CONSENSUS STATEMENT BY THE AMERICAN ASSOCIATION OF CLINICAL ENDOCRINOLOGISTS AND AMERICAN COLLEGE OF ENDOCRINOLOGY ON THE COMPREHENSIVE TYPE 2 DIABETES MANAGEMENT ALGORITHM--2016 EXECUTIVE SUMMARY. (2016, background): “When added to maximal statin therapy, these once- or twice-monthly injectable agents reduce LDL-C by approximately 50%, raise HDL-C, and have favorable effects on other lipids (191-197).”
- 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. (2019, background): “Several outcome trials assessing the effects of adding a PCSK9 inhibitor to high-intensity statin therapy have now been reported, with similar proportional reductions in major vascular events in women and men.(120,286,290)”