Lower Risk for Adverse CV Outcomes With Evolocumab, With/Without Diabetes
The study was double blinded and is the largest study on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to date.
Evolocumab may decrease the risk for adverse cardiovascular events in patients with and without diabetes, without increasing the risk for new-onset diabetes or worsening glycemia in patients without diabetes or prediabetes, according to a study published by The Lancet Diabetes & Endocrinology.
Researchers identified a total of 11,031 individuals (40% with diabetes) at 1242 sites in 49 countries and randomly assigned them (1:1) to receive subcutaneous evolocumab (140 mg every 2 weeks or 420 mg once per month, per patient preference) or placebo injections with follow-up visits at weeks 2, 4, 12, and every 12 weeks thereafter for an average of 2.2 years. The study was double blinded and is the largest study on a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor to date. Significant differences in baseline characteristics existed between patients with and without diabetes.
Results from the FOURIER study (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk; ClinicalTrials.gov identifier: NCT01764633) determined that evolocumab reduced adverse cardiovascular outcomes significantly in patients with and without diabetes at baseline (hazard ratio (HR) 0.83; 95% CI, 0.75-0.93; P =.0008 and HR 0.87; 95% CI, 0.79-0.96; P =.0052, respectively). In addition, it was found that evolocumab did not increase the risk for new-onset diabetes in patients without diabetes or prediabetes at baseline (HR 1.05, 0.94-1.17 and HR 1.00, 0.89-1.13, respectively). Of patients who started insulin therapy during the study, 5.3% were being treated with evolocumab and 6.4% were being treated with placebo (P =.037).
Additionally, it can be noted that evolocumab reduced low-density lipoprotein (LDL) cholesterol level in the subgroups of patients with diabetes by 57% (95% CI, 56-58; P <.0001) and by 60% in patients without diabetes (95% CI, 60-61; P <.0001).
The investigators concluded that overall, the use of evolocumab in patients with and without diabetes lowered LDL cholesterol and decreased the risk for adverse cardiovascular outcomes. Further, in patients with and without prediabetes, it did not increase the risk for new-onset diabetes and did not worsen glycemia.
Based on these results, clinicians should consider the “use of evolocumab in patients with atherosclerotic cardiovascular disease and diabetes” as it is shown to be safe and effective for those with and without diabetes.
Sabatine MS, Leiter LA, Wiviott SD, et al. Cardiovascular safety and efficacy of the PCSK9 inhibitor evolocumab in patients with and without diabetes and the effect of evolocumab on glycaemia and risk of new-onset diabetes: a prespecified analysis of the FOURIER randomised controlled trial [published online September 15, 2017]. Lancet Diabetes Endocrinol. doi:10.1016/S2213-8587(17)30313-3