Physicians' Academy for Cardiovascular Education

Very low LDL-C levels are safe and effective in high-risk post-ACS patients

Long-term Safety and Efficacy of Achieving Very Low Levels of Low-Density Lipoprotein Cholesterol: A Prespecified Analysis of the IMPROVE-IT Trial

Literature - Giugliano RP, Wiviott SD, Blazing MA, et al. - JAMA Cardiol. 2017; published online ahead of print


The IMPROVE-IT study showed that the combination of ezetimibe and simvastatin improved cardiovascular (CV) outcomes in patients with a recent acute coronary syndrome (ACS), compared with simvastatin monotherapy [1]. However, there are concerns about lowering cholesterol too much, since there are data showing an association with an increased risk for cancer, intracranial haemorrhage and death, whereas experimental data suggest that high doses of statins may cause brain and optic pathology [2-5].

In this pre-specified analysis, the safety and efficacy of very low LDL-C levels (<30 mg/dL) at 1 month were assessed, using data from 15 281 patients included in the IMPROVE-IT study. Patients were subdivided based on quartiles of LDL-C level at month 1 (<30, 30-49, 50-69 and ≥70 mg/dL).

Main results


Very low LDL-C levels at 1 month were associated with a similar safety profile compared with higher LDL-C levels. Moreover, LDL-C levels below currently recommended targets were associated with even further numerical reductions in CV events. These results support the use of intensive lipid-lowering therapy in very high-risk post-ACS patients.


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