increase in clinical and lab side effects vs. those with higher LDL-C or control groups in properly randomized studies.

The CVD events and IVUS data show additional benefits from low  (<40 mg/dL) and very low (<25 mg/dL) levels of LDL and increase CVD events when LDL remained elevated.

These evidences are derived from recent PCSK9 inhibitor trials, ODYSSEY LONG TERM (Alirocumab) and FOURIER (Evolocumab). Based on current evidence, the real safety concern is undertreatment of LDL rather than very low LDL. It is very hard to argue that we should reduce the dose of statin simply because the LDL is very low.