Published September 13, 2017 CARDIOVASCULAR Ultra-Low Appears to Be Better for LDL Cholesterol in High-Risk Patients By staff Boston—Are ultra-low LDL cholesterol levels too reduced for a high-risk population?A new study published in The Lancet and presented at the European Society of Cardiology meeting in Barcelona, Spain, suggests they are not. The new analysis led by Brigham and Women’s Hospital researchers finds that even LDL levels less than 10 mg/dL safely continue to lower risk of cardiovascular events. Questions about the safety of extremely low levels were raised with approval of PCSK9 inhibitors, which can substantially drive down LDL cholesterol beyond current treatment targets. An earlier clinical trial conducted by Brigham and Women’s confirmed the safety of the PCSK9 inhibitor evolocumab and found that, when added to statin therapy, it resulted in a significant reduction in the risk of cardiovascular events. The recent analysis investigated whether LDL could reach a level below which there would be no added clinical benefit but, possibly, a negative effect.In their analysis the researchers employed data from the Further Cardiovascular OUtcomes Research with PCSK9 Inhibition in subjects with Elevated Risk (FOURIER) trial, which found that patients treated with evolocumab and statin therapy had a 20% reduction in the risk of cardiovascular death, myocardial infarction, or stroke. Included were 25,982 patients who were evaluated following 1 month of treatment.Results indicated that the risk of cardiovascular events—cardiovascular death, heart attack, and stroke—over 2.2 years continuously declined as LDL cholesterol levels decreased to below 20 mg/dL (0.5 mmol/L). In fact, the study determined that participants who achieved an LDL-C of less than 10 mg/dL (0.26 mmol/L) had a more than 40% lower risk of cardiovascular events than those with an LDL cholesterol equal to or greater than 100 mg/dL (2.6 mmol/L).“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 70 mg/dL (1.8 mmol/L) can further reduce the risk for an adverse cardiovascular event, with no major safety concerns,” explained conference presenter Robert P. Giugliano, MD, a senior investigator in the TIMI Study Group at Brigham and Women’s Hospital and a cardiovascular physician.At the same time, no significant association was established between LDL-C level and prespecified adverse events. In subanalyses, the study team found that very low LDL cholesterol levels did not have a negative impact on cognition, reaction time, or memory, or on nine other safety endpoints.“Given the previous results from the FOURIER trial and the findings from this new analysis, patients—particularly those at a high risk for future cardiovascular events— should review their LDL cholesterol with their physicians and discuss whether it could be beneficial to lower that level beyond what they have achieved with diet, lifestyle modifications and statin therapy,” Giugliano suggested.« Click here to return to Weekly News Update.