Long-term treatment with evolocumab, a proprotein convertase subtilisin kexin type 9 (PCSK9) inhibitor, was found to be safe and well tolerated and led to sustained low-density lipoprotein cholesterol (LDL-C) lowering in adults with atherosclerotic cardiovascular disease (ASCVD) for up to 8.4 years, according to data from the FOURIER open-label extension (OLE) studies.
The multicenter OLE studies (ClinicalTrials.gov Identifier: NCT02867813, NCT03080935) evaluated the long-term safety and tolerability of evolocumab in a total of 6635 adults with clinically evident ASCVD who had completed the FOURIER study (ClinicalTrials.gov Identifier: NCT01764633). Patients self-administered evolocumab (either 140mg every 2 weeks or 420mg monthly); study visits were at week 12 and then every 24 weeks thereafter. Patients were evaluated for a median follow up of up to 5 years; the maximum exposure to evolocumab was 8.4 years when the FOURIER and OLE studies were combined.
Findings showed that treatment with evolocumab resulted in clinically significant and sustained reduction in LDL-C levels, with 80% of patients achieving an LDL-C level of less than 55mg/dL at week 12. Moreover, evolocumab was associated with a consistent LDL-C reduction of 58% from baseline over long-term follow up (week 260).
Exploratory analysis of the OLE studies also showed that patients who received evolocumab in the parent study had a 15% lower risk of cardiovascular (CV) death, myocardial infarction (MI), stroke, hospitalization for unstable angina or coronary revascularization (hazard ratio [HR] 0.85; 95% CI, 0.75–0.96; P =.008), a 20% lower risk of CV death, MI or stroke (HR 0.80; 95% CI, 0.68–0.93; P =.003), and a 23% lower risk of CV death (HR 0.77; 95% CI, 0.60–0.99; P =.04) compared with those who received placebo.
“These findings fill a significant gap in the body of research on the long-term safety and efficacy of PCSK9 inhibitors,” said Principal investigator Dr Michelle O’Donoghue of Brigham and Women’s Hospital, Boston, US. “Importantly, earlier initiation of LDL-C lowering with evolocumab combined with consistent long-term use, further reduced the risk of major cardiovascular events and cardiovascular mortality in this study.”
Evolocumab is marketed under the brand name Repatha. It is currently approved as an adjunct to diet and other LDL-C-lowering therapies in patients with primary hypercholesterolemia or mixed dyslipidemia, and heterozygous or homozygous familial hypercholesterolemia. It is also indicated to reduce the risk of myocardial infarction, stroke, and coronary revascularization in patients with established cardiovascular disease.
- New Amgen data at ESC 2022 show long-term LDL-C lowering with Repatha® (evolocumab) was well-tolerated for more than 8 years. News release. Amgen. Accessed August 29, 2022. https://www.multivu.com/players/English/8812855-new-amgen-data-esc-2022/
- Long-term evolocumab therapy leads to further reductions in cardiovascular events. News release. Amgen. Accessed August 29, 2022. https://www.escardio.org/The-ESC/Press-Office/Press-releases/Long-term-evolocumab-therapy-leads-to-further-reductions-in-cardiovascular-events