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BMJ Rapid Recommendations on use of proprotein convertase subtilisin/kexin 9 inhibitors and ezetimibe to reduce cardiovascular risk
  1. Harvey D White
  1. Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland, New Zealand
  1. Correspondence to Prof Harvey D White, Green Lane Cardiovascular Research Unit, Auckland City Hospital, Auckland 1142, New Zealand; harveyw{at}

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The new BMJ Rapid Recommendations addressed the following question: should we add another lipid-lowering drug in adults with low-density lipoprotein-cholesterol (LDL-C) over 1.8 mmol/L using a maximal dose of statins or intolerant to statins?1 Why is this question important? Both proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and ezetimibe have been shown to reduce LDL-C by approximately 60% and approximately 20%, respectively, and correspondingly may reduce major adverse cardiovascular events (MACE), including all-cause 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 LDL-C treatment targets. Examples of thresholds include the European Society of Cardiology (ESC) guidelines, which recommend an LDL-C target of 1.4 mmol/L for patients at very high cardiovascular risk,2 and the American College of Cardiology/American Heart Association (AHA/ACC) guidelines, which set a less aggressive LDL-C target of 1.8 mmol/L.3

The new guideline is a collaborative initiative from the MAGIC Evidence Ecosystem Foundation ( and the BMJ. The authors performed a systematic review and network meta-analysis 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.4

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.5 To apply these recommendations, clinicians need to calculate patients’ individual absolute cardiovascular risks using risk calculators applicable to specific geographical regions.

Guideline panel and patient involvement

The multiprofessional panel included three cardiologists, nine general practitioners (GPs), eight general internists, one endocrinologist, one geriatrician, one epidemiologist, one oncologist and three patient partners, who …

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  • Correction notice This article has been corrected since it was first published online. The title and DOI were incorrect for reference 4, and it has now been amended.

  • Contributors HDW is responsible for planning, conduct and reporting of the work described in the article.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests HDW has received grant support paid to the institution and fees for serving on the steering committees of the ODYSSEY trial from Sanofi and Regeneron Pharmaceuticals, the ISCHEMIA and the MINT studies from the National Institutes of Health, the STRENGTH trial from Omthera Pharmaceuticals, the HEART-FID study from American Regent, the DAL-GENE study from DalCor Pharma UK, the AEGIS-II study from CSL Behring, the SCORED and SOLOIST-WHF from Sanofi Aventis Australia, and the CLEAR OUTCOMES study from Esperion Therapeutics. HDW is a member of the Cholesterol Treatment Trialists’ Collaboration.

  • Provenance and peer review Commissioned; internally peer reviewed.

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