Does Lowering LDL-C to Ultra-Low Levels Provide Additional Benefit?
Aggressive reduction of LDL cholesterol down to ultra-low levels of <10mg/dL was associated with a further reduction of risk for cardiovascular events in a high-risk population, according to research presented at the European Society of Cardiology (ESC) Congress 2017 in Barcelona, Spain. The findings were also published in The Lancet.
A previous clinical study, the FOURIER (Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk) trial, demonstrated that evolocumab (Repatha; Amgen), a PCSK9 inhibitor, was safe and effective in reducing the risk of cardiovascular events when added to statin therapy. Using data from this trial, researchers explored the “floor effect"—a limit where there would be no additional clinical benefit seen with lowering LDL cholesterol—in 25,982 patients. Additionally, the analysis investigated whether there was any negative impact associated with ultra-low LDL cholesterol levels.
The researchers observed these endpoints according to degree of LDL cholesterol reduction after 1 month of treatment. The risk for cardiovascular events, including cardiovascular death, myocardial infarction, and stroke over 2.2 years continuously declined as LDL cholesterol levels decreased to 20mg/dL (0.5mmol/L). Patients who achieved a level <10mg/dL (0.26mmol/L) had an even lower risk of cardiovascular events by >40% compared to individuals with a level of ≥100mg/dL (2.6mmol/L).
Neurocognitive events, including cognition impact, reaction time or memory, and nine other safety endpoints were compared in the sub-analyses of the study; no differences were found across the varied LDL cholesterol levels.
"Our findings demonstrate that there is essentially no floor effect, and that lower levels translated to a greater reduction in risk. Among high-risk patients, achieving a LDL cholesterol level far below the most common treatment target of 70mg/dL (1.8 mmol/L) can further reduce the risk for an adverse cardiovascular event, with no major safety concerns," said Robert P. Giugliano, MD, a senior investigator in the TIMI Study Group at Brigham and Women's Hospital. The TIMI Group conducted the data analyses presented in the paper.
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