Can LDL-C Be Too Low?

Summary for Physicians:

While lowering LDL-C levels is crucial for reducing the risk of atherosclerotic cardiovascular disease (ASCVD) and recurrent events, the question of how low LDL-C levels should be reduced remains important in clinical practice. Evidence supports significant reductions in LDL-C levels, but concerns exist regarding potential risks when LDL-C levels are lowered excessively.

How Low Is Too Low in LDL-C Level Lowering?

1. No Clear Threshold for Harm: Current clinical evidence suggests that lowering LDL-C to very low levels (even below traditional target ranges) does not lead to significant harm in high-risk patients, including those with a history of ACS. Large clinical trials, such as those involving PCSK9 inhibitors, have demonstrated that LDL-C levels as low as 20 to 30 mg/dL are safe and beneficial, with no clear increase in adverse events such as cancer or neurological issues.
2. Safety Considerations: Although there is no definitive lower limit for LDL-C, extreme reductions (eg, less than 20 mg/dL) in patients without cardiovascular disease may be associated with potential risks, including hormonal imbalances or other unknown long-term effects. However, in the context of secondary prevention (eg, post-ACS), the benefits of very low LDL-C levels in reducing recurrent cardiovascular events outweigh these potential risks.
3. Individualized Approach: While the general guidelines recommend target LDL-C levels of less than 70 mg/dL or even less than 55 mg/dL for high-risk patients post-ACS, individualized care is essential. Factors such as the patient's overall health, comorbidities, and response to therapy should be considered. In some patients with very high cardiovascular risk, aggressive LDL-C level lowering is necessary, and the benefits of achieving low levels outweigh concerns about possible risks.
4. Monitoring for Potential Risks: In patients on intensive lipid-lowering therapy (eg, statins plus PCSK9 inhibitors), regular monitoring for adverse effects, including muscle symptoms, liver function, and cognitive function, is important to ensure that the therapy is well tolerated.

In conclusion, while lowering LDL-C to very low levels is generally safe and beneficial in high-risk cardiovascular patients, monitoring and an individualized approach remain critical to avoid potential risks associated with extreme LDL-C level reductions.