Further LDL Lowering in Patients With Very Low LDL Reduces Vascular Events

From www.praticeupdate.com.
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Reducing low-density lipoprotein cholesterol (LDL-C) concentrations is one of the cornerstones of the primary and secondary prevention of cardiovascular disease. In general, most estimates suggest that for every ~1 mmol/L (or 39 mg/dL) reduction in LDL-C, the relative risk of cardiovascular events is reduced by about 20%. This risk reduction is largely linear across a broad range of starting LDL-C concentrations, but the data are derived from trials of statins, and few individuals start statin trials with LDL-C less than 2 mmol/L (77 mg/dL). The advent of non-statin drugs, such as ezetimibe and the PCSK9 inhibitors, means that LDL-C concentrations far lower than the 70 mg/dL typically cited in clinical guidelines can be achieved. Here, the authors report that in this group of patients who start with low LDL-C, further reduction in LDL-C continued to offer a reduction in the relative risk for major vascular events. For statins, that risk reduction was 22% per 1 mmol/L (39 mg/dL) reduction in LDL-C, and for ezetimibe, evolocumab, and anacetrapib that reduction was 21% for the same reduction in LDL-C. While the authors saw no increase in serious adverse events, and no increase in hemorrhagic stroke or diabetes, they did not report the effects on cataracts, which have been seen at higher rates among those with very low LDL-C. The data included in the meta-analysis are from randomized trials that are, by their nature, of relatively short duration, and thus may miss adverse effects that take time to develop. Nonetheless, the data are encouraging and add to the body of evidence that lowering LDL-C concentrations to very low levels offers continued cardiovascular risk and is associated with few adverse effects.