LDL-C Targets in Secondary Prevention: How Low Should We Go?

Purpose of Review: The benefits of lowering low-density lipoprotein cholesterol (LDL-C), mainly using high-intensity statin therapy, and its impact on decreasing the recurrence of atherosclerotic cardiovascular disease (ASCVD) in secondary prevention has been well established. With the advent of non-statin medications, particularly PCSK-9 inhibitors, which can lower LDL-C to very low levels not seen before, it is important to answer some important questions regarding LDL-C lowering and the uses of these medications in clinical practice: how low should we go with LDL-C reduction? Is there a threshold beyond which lower LDL-C is not associated with any benefit and possibly harm? Does the benefit derived from more aggressive LDL-C lowering justify the cost of additional therapies? Recent Findings: Our review has found overwhelming evidence to support the conclusion that lower achieved LDL-C levels correlate with a decreased burden of atherosclerosis and better clinical outcomes in secondary prevention. The concern for adverse effects with very low LDL-C levels is not backed by the literature, and side effects appear to be medication-specific. There still remains a question of the cost-effectiveness of some non-statin therapies particularly PCSK9 inhibitors, in spite of recent price decreases, and whether the benefit is worth the cost. Summary: It is prudent to always pursue an individualized patient-level approach to LDL-C lowering that considers the patient’s global cardiovascular risk, their side effect profile, and the cost-effectiveness of therapies in order to derive maximal benefit from aggressive lipid lowering.