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CV death risk decreases with evolocumab in atherosclerotic disease
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The risks for cardiovascular death, myocardial infarction and stroke are reduced in adults with atherosclerotic disease with or without diabetes treated with the PCSK9 inhibitor evolocumab, according to findings from the FOURIER trial presented at the European Association for the Study of Diabetes Annual Meeting and published simultaneously in The Lancet Diabetes & Endocrinology.
Marc S. Sabatine, MD, MPH, the Lewis Dexter, MD, Distinguished Chair in Cardiovascular Medicine at Brigham and Women’s Hospital, and colleagues evaluated data from FOURIER on 27,564 adults with atherosclerotic disease with (40%) or without diabetes randomly assigned to evolocumab (Repatha, Amgen) or placebo to determine its efficacy and safety and the effect on the risk for developing diabetes.
The primary outcome was a composite of CV death, MI, stroke, hospitalization for unstable angina or coronary revascularization. The key secondary outcome was a composite of CV death, MI or stroke. Median follow-up was 2.2 years.
Among the placebo group, the primary outcome occurred in more participants with diabetes than those without diabetes at baseline (17.1% vs. 13%; P < .0001). The secondary outcome also occurred in more participants with diabetes than those without diabetes (12.2% vs. 8.4%; P < .0001). Participants with diabetes in the placebo group had a higher risk for the primary (HR = 1.26; 95% CI, 1.13-1.4) and secondary outcomes (HR = 1.4; 95% CI, 1.23-1.6) compared with participants without diabetes in the placebo group.
In the evolocumab group, the risk for the primary outcome was reduced in participants with diabetes (HR = 0.83; 95% CI, 0.75-0.93) and without diabetes (HR = 0.87; 95% CI, 0.79-0.96). Further, evolocumab reduced the risk for the secondary outcome in participants with diabetes (HR = 0.82; 95% CI, 0.72-0.93) and without diabetes (HR = 0.78; 95% CI, 0.69-0.89).
No significant differences were observed between the evolocumab and placebo groups for adverse and serious adverse events regardless of diabetes status.
The risk for new-onset diabetes in participants without diabetes at baseline did not increase with evolocumab (HR = 1.05; 95% CI, 0.94-1.17).
“Evolocumab lowered LDL cholesterol and significantly reduced cardiovascular risk with similar relative efficacy in patients with and without diabetes,” the researchers wrote. “Due to their heightened baseline risk of cardiovascular events, patients with diabetes tended to have a greater absolute risk reduction with evolocumab therapy. Evolocumab did not increase the risk of new-onset diabetes, including in patients with prediabetes, nor did it worsen glycemia. These data suggest that use of evolocumab in patients with atherosclerotic cardiovascular disease and diabetes is particularly efficacious and that evolocumab treatment is equally safe in patients with and without diabetes.”
In an accompanying editorial, Luca A. Lotta, MD, PhD, and Simon J. Griffin, DM, both of the MRC epidemiology unit at the University of Cambridge School of Clinical Medicine in Cambridge, United Kingdom, wrote that the data “suggest that evolocumab is an effective and safe option for patients with diabetes and atherosclerotic disease.”
“If PCSK9 inhibitors, or other emerging therapies, have few adverse effects, including a minimal effect on diabetes risk, such findings might influence prescribing decisions,” they wrote. “However, in view of their high costs, access to PCSK9 inhibitors is likely to remain limited for the vast majority of the half a billion people with type 2 diabetes worldwide for the foreseeable future.” – by Amber Cox
References:
Lotta LA, Griffin SJ. Lancet Diabetes Endocrinol. 2017;doi:10.1016/S2213-8587(17)30321-2.
Sabatine MS, et al. Evolocumab in diabetes and diabetes risk: novelties from the FOURIER study. Presented at: European Association for the Study of Diabetes Annual Meeting; Sept. 11-15, 2017; Lisbon, Portugal.
Sabatine MS, et al. Lancet Diabetes Endocrinol. 2017;doi:10.1016/S2213-8587(17)30313-3.
Disclosures: Griffin reports he receives an honorarium and reimbursement expenses from AstraZeneca, Eli Lilly and Janssen. Lotta reports no relevant financial disclosures. Sabatine reports he receives grant support (through Brigham and Women’s Hospital) from Abbott Laboratories, Amgen, AstraZeneca, Critical Diagnostics, Daiichi-Sankyo, Eisai, Genzyme, Gilead, GlaxoSmithKline, Intarcia, Janssen Research and Development, The Medicines Company, MedImmune, Merck, Novartis, Poxel, Pfizer, Roche Diagnostics and Takeda, and honoraria for consulting from Alnylam, Amgen, AstraZeneca, Cubist, CVS Caremark, Esperion, Intarcia, Ionis, Janssen Research and Development, The Medicines Company, MedImmune, Merck and MyoKardia. Please see the study for all other authors’ relevant financial disclosures.