Thus far, safety data have been reassuring with respect to achievement of very low LDL-C with PCSK9 inhibitors. There is little experience in managing patients with very low LDL-C and considerable concern has arisen about whether the benefit-to-risk ratio for lowering LDL-C holds at these very low levels. As more aggressive LDL-C lowering approaches become increasingly common, with use of human monoclonal antibodies targeting proprotein convertase subtilisin-kexin type 9 (PCSK9), the accuracy of LDL-C assessment at very low levels gains importance.
#VERY LOW LDL CHOLESTEROL RANGE TRIAL#
Most major international guidelines endorse an LDL-C target of < 70 mg/dL for high-risk patients and the IMProved Reduction of Outcomes: Vytorin Efficacy International Trial (IMPROVE-IT) trial showed additional benefit from attaining even lower LDL-C levels (~50 mg/dL) by adding ezetimibe to statin therapy. LDL-C is the lipid parameter that is most widely used to guide clinical decision making. The critical importance of low-density lipoprotein cholesterol (LDL-C) lowering in cardiovascular disease management and prevention of atherothrombotic events is well established. More often than not, a Friedewald value < 40 mg/dL is underestimated, which translates into unnecessary safety alarms that could be reduced in half by estimation using our novel method. ConclusionsĮstimation of even lower LDL-C values (by Friedewald and novel methods) is even more inaccurate. Among those with Friedewald LDL–C < 15, 15 to < 25, and 25 to < 40 mg/dL, the classification was discordantly low in 94.9%, 82.6%, and 59.9% of individuals as compared with 48.3%, 42.4%, and 22.4% by novel estimation. We examined differences (estimate minus ultracentrifugation) and classification according to levels initiating additional safety precautions per clinical practice guidelines. In 191,333 individuals with Friedewald LDL-C < 70 mg/dL, we compared the accuracy of Friedewald and novel LDL-C values in relation to direct measurements by Vertical Auto Profile ultracentrifugation. We aimed to assess the accuracy of LDL-C estimation at very low levels by the Friedewald equation, the de facto clinical standard, and compare its accuracy with a novel, big data-derived LDL-C estimate. As the approach to low-density lipoprotein cholesterol (LDL-C) lowering becomes increasingly intensive, accurate assessment of LDL-C at very low levels warrants closer attention in individualized clinical efficacy and safety evaluation.
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