LDL Lowering After Acute Coronary Syndrome: Is Lower Better?

OPINION STATEMENT: Low density lipoprotein cholesterol (LDL-C) levels are a major risk factor for the development of acute coronary syndrome (ACS) and for recurrent events after ACS. Lowering LDL-C after ACS leads to a significant reduction in recurrent events and overall mortality. A lower limit at which LDL-C reduction fails to decrease risk has not been determined, and lowering LDL-C below current guideline-defined targets may provide incremental benefit. While the absolute risk is small, more intensive statin therapy is associated with a higher incidence of myopathy, rhabdomyolysis, liver enzyme abnormalities and incident diabetes, but not with an increase in malignancies or all-cause mortality. It is important that clinicians recognize ACS patients as being at very high risk, and provide these patients with intensive lifestyle and pharmacologic therapy for all modifiable risk factors. Within this framework, either a strategy of "intensive statin treatment after ACS" or a strategy of "aggressive LDL-C targets after ACS" would be appropriate based on currently available data. Combination lipid-lowering therapy does not have a firm evidence base at this point, but may be appropriate in patients with limited statin tolerance or very high baseline LDL-C levels. Newer therapies, such as LDL apheresis, antisense oligonucleotide sequences to apolipoprotein B (apoB) and preprotein convertase subtilin kexin 9 (PCSK9) inhibitors, are currently in clinical trials and may represent important advances in LDL-C lowering therapy in the future.