Study shows better results with evolocumab in adults with atherosclerotic cardiovascular disease
Evolocumab has been shown to reduce adverse cardiovascular events in combination with statin therapy compared to placebo plus statin therapy.
Results from the FOURIER and FOURIER open-label extension (OLE) Phase 3 studies of evolocumab (Repatha; Amgen) in adults with atherosclerotic cardiovascular disease (ASCVD) revealed that achieving and maintaining a low-density lipoprotein cholesterol (LDL-C) levels
“The current analysis further confirms that achieving very low long-term LDL-C is not associated with any new safety signals and correlates with reduced cardiovascular events in patients with Alzheimer’s disease. atherosclerotic cardiovascular disease,” said David M. Reese, MD, vice president of research and development at Amgen, in a press release. “Repatha continues to be at the forefront of PCSK9i research, with the longest-running safety and efficacy trial data among PCSK9i treatments for cardiovascular disease, providing crucial information to patients and doctors who manage this disease.
The phase 3, randomized, placebo-controlled FOURIER trial was designed to analyze whether treatment with evolocumab in combination with statin treatment compared to placebo plus statin treatment reduced adverse cardiovascular events.
The primary endpoint of the trial was the time to first occurrence of cardiovascular death, MI, stroke, hospitalization for unstable angina or coronary revascularization. The secondary endpoint of the trial was time to first occurrence of cardiovascular death, MI, or stroke.
Eligible patients with elevated cholesterol and clinically evident ASCV at over 1,300 study sites worldwide were randomized to receive evolocumab 140 mg subcutaneously every 2 weeks or 420 mg monthly plus an effective dose of statin or a subcutaneous placebo every 2 weeks or monthly plus an effective dose of statin. Optimized statin therapy was defined as atorvastatin 20 mg or equivalent per day with a recommendation of at least atorvastatin 40 mg or equivalent per day when approved.
FOURIER-OLE was designed to evaluate the long-term safety of evolocumab in patients who completed the FOURIER study. The study enrolled 5035 and 1600 subjects who completed the FOURIER study to receive open-label evolocumab and were followed for a median of 5 and 4.6 years, respectively.
All patients in the extension program were treated with open-label evolocumab without concomitant placebo during this period. Not all patients participated in the baseline FOURIER-OLE characteristics, and these individuals were broadly comparable between the originally randomized treatment arms, allowing exploratory comparisons reasonably without confounding between the groups, according to the study.
A total of 26,389 patients had early LDL-C, of which 19,960 were in FOURIER alone with a median follow-up of 2 years and 6,429 of them also participated in FOURIER-OLE with a median follow-up of about 7 years old.
The analysis examined the association between reaching different LDL-C levels with the incidence of cardiovascular and safety outcomes up to 8.6 years of follow-up. Over 3,500 patients between the two studies achieved LDL-C levels
Over 77,470 patient-years of follow-up, there was a monotonic relationship between lower LDL-C levels and a reduced risk of CV death, MI, stroke, coronary revascularization, or hospitalization for angina unstable.
A similar relationship was observed between LDL-C levels achieved and the risk of FOURIER’s key secondary efficacy endpoint of CV death, MI or stroke. Additionally, there was no significant association between lowering LDL-C attainment and the risk of serious adverse events (AEs), neurocognitive events, development of new diabetes, AEs related cataract, a new or progressive malignancy, the occurrence of a hemorrhagic stroke. , muscle events or non-cardiovascular deaths, depending on the study.
“Until now, there has been a gap in medical knowledge about the long-term efficacy and safety implications of very low LDL-C
AMGEN presents new repatha® (evolocumab) data at AHA 2022. Amgen. November 7, 2022. Accessed November 8, 2022. https://wwwext.amgen.com/newsroom/press-releases/2022/11/amgen-presents-new-repatha-evolocumab-data-at-aha-2022