Long-term LDL cholesterol reduction with evolocumab reduces events, including CV death
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Data from an open-label extension of the FOURIER study show use of the PCSK9 inhibitor evolocumab for more than 7 years led to durable reductions in LDL and a reduction in CV events, including CV death, according to a speaker.
In the FOURIER-OLE study, presented at the European Society of Cardiology Congress, researchers also found that earlier initiation of evolocumab (Repatha, Amgen) was associated with continued accrual of CV benefit over years, arguing for an earlier initiation of a marked and sustained LDL reduction to maximize clinical benefit.
“The open-label extension demonstrated that early and sustained reductions in LDL with evolocumab translated into additional cardiovascular benefit when compared to patients who were started on evolocumab later,” Michelle L. O’Donoghue, MD, MPH, FAHA, cardiovascular medicine specialist at Brigham and Women’s Hospital and associate professor of medicine at Harvard Medical School, told Healio. “The follow-up period during the parent FOURIER study was limited to 2.2 years, and we saw that the cardiovascular benefit became more apparent during the parent study with time. This was confirmed during the extension study, as there was not only a reduction in the traditional composite outcome of cardiovascular events, but also a significant reduction in cardiovascular mortality that was not seen in the parent study. There was also no apparent safety signal despite achieving extremely low LDL-C levels — an average of 30 mg/dL — over a period of several years.”
As Healio previously reported, inhibition of PCSK9 with evolocumab on a background of statin therapy lowered LDL levels to a median of 30 mg/dL and reduced the risk for CV events at 48 weeks; there was no effect observed during the parent study for CV death.
The open-label extension study enrolled 6,635 participants who completed FOURIER, including 3,355 randomly assigned evolocumab (140 mg once every 2 weeks or 420 once monthly) and 3,280 originally assigned placebo who then self-injected open-label evolocumab. Study visits occurred at week 12 and then every 24 weeks and included clinical assessments and fasting lipids. Researchers assessed long-term safety and tolerability of the drug; an independent clinical events committee reviewed major adverse CV events. Median follow-up was 5 years; maximum exposure to evolocumab across both studies was 8.4 years.
The findings were simultaneously published in Circulation.
During FOURIER-OLE, participants originally assigned evolocumab had a 15% lower risk for CV death, MI, stroke, hospitalization for unstable angina or coronary revascularization compared with participants assigned placebo (HR = 0.85; 95% CI, 0.75-0.96; P = .008), as well as a 20% lower risk for CV death, MI or stroke (HR = 0.8; 95% CI, 0.68-0.93; P = .003), and a 23% lower risk for CV death (HR = 0.77; 95% CI, 0.6-0.99; P = .04).
“Some patients treated with evolocumab during the parent study ultimately had more than 8 years of exposure to evolocumab and no concerning safety signals were seen,” O’Donoghue told Healio. “Overall, the findings support the concept that marked LDL reduction with evolocumab is safe and has greater accrual of cardiovascular benefit with more prolonged treatment.”
Reference:
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O’Donoghue ML, et al. Hot Line 8. Presented at: European Society of Cardiology Congress; Aug. 26-29, 2022; Barcelona, Spain (hybrid meeting).
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