Clinical trials of statins have shown that lower low-density lipoprotein (LDL) cholesterol levels lead to lower cardiovascular risk. Nonstatin drugs are now available that can be added to statins to reduce LDL cholesterol levels further. A recent meta-analysis was conducted to determine the clinical benefits and safety of lowering of LDL cholesterol to below current guideline targets in patients with already very low levels. Data on statins were drawn from a meta-analysis of 26 trials that included a subgroup of patients with a baseline mean LDL cholesterol level of 1.7 mmol/L (66 mg/dL). A Medline search yielded data from trials of adding a nonstatin to a statin in patients starting with a mean or median LDL cholesterol level of 1.8 mmol/L (70 mg/dL) or less. Major vascular events were defined as coronary heart death, myocardial infarction, stroke, and coronary revascularization.

The meta-analysis of statin trials found a 22% relative risk reduction in major vascular events per 1 mmol/L reduction in LDL cholesterol. In the three trials of nonstatins, adding ezetimibe, evolocumab, and anacetrapib, which is no longer prescribed, to statin therapy lowered LDL cholesterol by 0.3 mmol/L (13 mg/dL), 1.1 mmol/L (42 mg/dL), and 0.3 mmol/L (11 mg/dL), respectively. Benefits were seen in patients who achieved an LDL cholesterol level as low as 0.5 mmol/L (21 mg/dL).

In addition, reductions in LDL cholesterol did not increase the risk of serious adverse events, myalgias or myositis, elevated aminotransferase levels, new-onset diabetes, hemorrhagic stroke, or cancer in any of the trials after two to six years of follow-up.

Because of the consistent reductions in cardiovascular risk even in patients with very low LDL cholesterol levels at baseline, the authors predict that reducing target levels to as low as 0.5 mmol/L would further reduce cardiovascular risk.-KR

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