New Repatha data support lower LDL-C levels for high-risk cardiovascular patients

No evidence of a leveling off of effect and no new safety concerns were identified in this analysis.

"With this analysis, we've further demonstrated the safety and efficacy of achieving an LDL-C well below current targets," said Robert P. Giugliano, Brigham and Women's Hospital and Harvard Medical School, Boston and lead author on the analysis. "These findings from the first analysis of a large cohort of patients to achieve such ultra-low LDL-C levels support the use of intensive lipid-lowering therapies, such as the combination of evolocumab and statin therapy, in high-risk patients to safely reduce the risk of another cardiovascular event."

Approximately 26,000 patients from the Repatha cardiovascular outcomes study were followed for a median of 2.2 years and stratified post-randomization into five prespecified groups irrespective of treatment allocation based on achieved LDL-C at week four from baseline: <0.5 mmol/L (which converts to less than 20 mg/dL), 0.5-<1.3 mmol/L, 1.3-<1.8 mmol/L, 1.8-<2.6 mmol/L, and =2.6 mmol/L). Rates for the primary and secondary composite endpoints and cognitive function testing, as well as safety events, including cancer, hemorrhagic stroke, new onset diabetes, cataract, neurocognitive dysfunction and non-cardiovascular death were compared across these five groups.

The analysis demonstrated that there was a highly significant progressive relationship between lower LDL-C and a lower risk of the primary composite endpoint. A similar progressive reduction in the key secondary composite endpoint, which included heart attack, stroke or cardiovascular death, was also observed across all five groups. There was no meaningful difference in the safety profile across the five groups, including the group with the lowest achieved LDL-C level. Lastly, patients were more likely to achieve very low LDL-C levels when treated with Repatha and statin therapy versus statin alone.

"Scientific evidence demonstrating the strong progressive association between lowering LDL-C and the risk reduction of cardiovascular events in patients with established atherosclerotic cardiovascular disease continues to grow," said Sean E. Harper, executive vice president of R&D at Amgen. "For patients who have already experienced an event, such as a heart attack or stroke, this analysis reinforces that the intensive LDL-C lowering provided with Repatha helps patients reduce their risk of another cardiovascular event."