In the treatment of diabetes and atherosclerotic cardiovascular disease (CVD), adding PCSK9 inhibitor alirocumab to statin therapy allowed high-risk patients to achieve reduced low-density lipoprotein cholesterol (LDL-C) and other atherogenic lipid goals. Additionally, alirocumab was significant in reducing LDL-C in patients who could not tolerate high statin doses or where statins were ineffective, according to a study published in Diabetes, Obesity and Metabolism.
International guidelines for managing diabetes and atherosclerotic CVD recommend statin therapy to reduce LDL-C levels; however, recent evidence shows that these patients are not achieving their LDL-C goals on statins alone. This post hoc study sought to evaluate the safety and efficacy of alirocumab treatment on a cohort of 984 individuals diagnosed with type 1 or type 2 diabetes and atherosclerotic CVD.
Pooling patients from 9 ODYSSEY Phase 3 trials, the study participants were characterized by alirocumab dosage: patients received alirocumab 150 mg, patients receiving alirocumab 75 mg with possible increase to 150mg (alirocumab 75/150), control (placebo/ezetimibe), and patients with or without background statin use. To determine efficacy end points, study investigators analyzed changes in the participants’ lipid profiles over 24 weeks of biweekly administered alirocumab treatment. Safety data were evaluated based on the placebo-controlled and ezetimibe-controlled groups.
Patients with background statin use showed a reduction in LDL-C levels from baseline by 61.5% in the alirocumab 150 group and 46.4% in the alirocumab 75/150 group vs placebo, and a 48.7% reduction in the alirocumab 75/150 group vs ezetimibe. A 54.9% reduction in LDL-C levels was observed in the alirocumab 75/150 group without statin usage vs the ezetimibe-controlled group. All control groups showed either an insignificant decrease or a modest increase in LDL-C levels from baseline. By week 24, more alirocumab recipients achieved their treatment goals of LDL-C <70 mg/dL and <55 mg/dL than individuals in the control groups.
Secondary end points included a reduction in non-high-density lipoprotein cholesterol and apolipoprotein B levels across all alirocumab groups compared with control groups. Less than 5% of patients reported muscle-related adverse events such as myalgia with equal frequency across all groups; although higher in the alirocumab groups, 5% or less described mild injection-site reactions. Limitations of the study include the nature of post hoc analysis and non-randomized subgroups. The number of participants without background statin therapy was small and could have contributed to certain discrepancies among in baseline data.
Based on data evaluated from this study, updated treatment guidelines now recommend adding a lipid-lowering therapy in the treatment of diabetes or atherosclerotic CVD when statins are insufficient or if patients are unable to tolerate high statin doses. In addition, the study indicates alirocumab is effective in reducing major adverse cardiovascular events by helping patients achieve reduced LDL-C goals and should be considered in the treatment of high-risk individuals.
This study was supported by Sanofi and Regeneron Pharmaceuticals, Inc.
Ganda OP, Plutzky J, Sanganalmath SK, et al. Efficacy and safety of alirocumab among individuals with diabetes mellitus and atherosclerotic cardiovascular disease in the ODYSSEY phase 3 trials [published online May 26, 2018]. Diabetes Obes Metab. doi: 10.1111/dom.13384