BMJ Rapid Recommendations on use of proprotein convertase subtilisin/kexin 9 inhibitors and ezetimibe to reduce cardiovascular risk

Abstract

The new BMJ Rapid Recommendations addressed the following question: should we add another lipidlowering drug in adults with lowdensity lipoproteincholesterol (LDLC) over 1.8 mmol/L using a maximal dose of statins or intolerant to statins? Why is this question important? Both proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe have been shown to reduce LDLC by approximately 60% and approximately 20%, respectively, and correspondingly may reduce major adverse cardiovascular events (MACE), including allcause death, cardiovascular death, myocardial infarction (MI) and stroke. However, the benefit of ezetimibe is small and PCSK9 inhibitors are very costly. Both drugs have adverse effects which must be considered when balancing recommendations to achieve maximal benefit and minimal harm. Current guidelines recommend differing LDLC treatment targets. Examples of thresholds include the European Society of Cardiology (ESC) guidelines, which recommend an LDLC target of 1.4 mmol/L for patients at very high cardiovascular risk, and the American College of Cardiology/American Heart Association (AHA/ACC) guidelines, which set a less aggressive LDLC target of 1.8 mmol/L. The new guideline is a collaborative initiative from the MAGIC Evidence Ecosystem Foundation (www.magicproject. org) and the BMJ. The authors performed a systematic review and network metaanalysis of 14 trials, with 83 660 participants, to define the absolute incremental beneficial effects of ezetimibe and PCSK9 inhibitors to statins, and this is published simultaneously in the BMJ. The guideline represents a shift from the traditional focus on lipid level goals to a focus on reducing an individual’s absolute cardiovascular risk. Few other guidelines specifically do this. To apply these recommendations, clinicians need to calculate patients’ individual absolute cardiovascular risks using risk calculators applicable to specific geographical regions.