A meta-analysis revealed that there is a consistent relative risk reduction in major vascular events per further reduction in low-density lipoprotein cholesterol (LDL-C) in patient populations starting as low as a median of 1.6 mmol/L (63 mg/dL) and achieving levels as low as a median of 0.5 mmol/L (21 mg/dL), with no offsetting adverse effects. In the subgroup of patients from the meta-analysis of statins with a mean LDL-C in the control arm of 1.7 mmol/L (65.7 mg/dL), 1922 major vascular events occurred and the risk ratio (RR) for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.78. For 3 trials of nonstatin LDL-C–lowering therapies added to statins, there were 50 627 patients, the median LDL-C in the control arms ranged from 1.6 to 1.8 mmol/L (63 to 70 mg/dL), and 9570 major vascular events occurred. Nonstatin therapy lowered LDL-C by 0.3 to 1.2 mmol/L (11 to 45 mg/dL), and the RR for major vascular events per 1-mmol/L (38.7-mg/dL) reduction in LDL-C was 0.79. For statins and nonstatins combined, the RR was 0.79. LDL-C lowering was not associated with an increased risk of serious adverse events, myalgias and/or myositis, elevation in the level of aminotransferases, new-onset diabetes, hemorrhagic stroke, or cancer. As the clinical benefit per millimoles per liter reduction in LDL-C was virtually identical for statins, ezetimibe, PCSK9 inhibition, and CETP inhibition, which supports the notion that the reduction in LDL-C is the primary driver of clinical benefit. LDL-C–lowering therapies tend to produce the same relative percentage lowering of LDL-C regardless of starting levels, the absolute lowering of LDL-C and therefore the relative and absolute risk reductions will mathematically be a function of the baseline LDL-C. The findings suggest further lowering of LDL-C thresholds to further reduce cardiovascular risk. Source: https://jamanetwork.com/
