Cardiovascular mortality after intensive LDL-Cholesterol lowering: Does baseline LDL-Cholesterol really matter?

It remains controversial whether reductions in cardiovascular mortality after intensive lowering of low density lipoprotein cholesterol (LDL-C) depend on baseline LDL-C levels. To reassess these findings, in this brief report, we performed an updated literature search through February 2020 and selected randomized controlled trials which reported cardiovascular mortality and major adverse cardiovascular events (MACE) as outcomes. We included 53 randomized controlled trials (329,897 patients) of LDL-C lowering therapies (statin, ezetimibe and PCSK9 inhibitors) and stratified the meta-analysis according to the baseline LDL-C thresholds. Our meta-analysis found that each 38.7 ​mg/dL (1 ​mmol/L) lowering in LDL-C reduced the risk of cardiovascular mortality (RR, 0.85; 95% CI, 0.81-0.89), but this varied by baseline LDL-C of those in the trials (P ​= ​0.04 for interaction). The risk reduction in cardiovascular mortality was limited to trials with baseline LDL-C of >100 ​mg/dL. In contrast, the reduction in MACE was independent of baseline LDL-C levels. These findings were consistent in primary and secondary prevention settings for both outcomes and by sex for MACE. Our results support the professional cholesterol guidelines which recommend achieving a ≥50% reduction in LDL-C from baseline for high-risk patients.