Call to lower Australian LDL-C targets

The release of new European guidelines on dyslipidaemias has called Australia’s LDL-C targets into question.

The Australian LDL cholesterol (LDL-C) targets in secondary prevention patients are being called into question following the recent publication of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) guidelines on dyslipidaemias.¹

For very-high-risk patients in secondary prevention, the guidelines recommend a new LDL-C goal of <1.4 mmol/L and an LDL-C reduction of at least 50% from baseline. For those with recurrent events within two years while taking maximally tolerated statin therapy, a goal of <1 mmol/L for LDL-C may be considered.¹

According to an article recently published in MJA Insight by clinical cardiologist and Professor of Medicine at Flinders University Philip Aylward, the Australian LDL-C targets for patients at high risk of cardiovascular events should be revised to <1.4 mmol/L to match the European guidelines.²

“In Australia, various guidelines suggest a target of <1.8 mmol/L for LDL-C for secondary prevention patients.³ However, the new target for patients post an ACS [acute coronary syndrome] or otherwise at very high risk should be <1.4 mmol/L,” said Professor Aylward.

“Mendelian randomisation studies have confirmed the critical role of LDL-C in atherosclerotic plaque formation and related subsequent cardiovascular events. Lowering LDL-C reduces cardiovascular events, including death, myocardial infarction (MI) and stroke.⁴

“To achieve an LDL-C target of <1.4mmol/L many patients will require not only high-intensity statin and ezetimibe but additional therapies. Currently an effective additional therapy is a PCSK9 inhibitor.”

One of the main updates since the 2016 European guidelines on dyslipidaemias is the Class IA recommendation of PCSK9i therapy as secondary prevention. This recommendation is for patients at very high risk of not achieving their LDL-C goal after 4–6 weeks of the maximum-tolerated dose of a statin and ezetimibe.¹

“The new European clinical guidelines represent a significant step forward in comparison to the previous guidelines. There are broader recommendations for lowering LDL-C, including a focus beyond statin therapy and more intensive reduction of LDL-C across CV [cardiovascular] risk categories, based on safety and efficacy results from trials including ODYSSEY OUTCOMES⁵ and FOURIER⁶,” said Professor Aylward.

The new guidelines are supported by data from ODYSSEY OUTCOMES, a multicentre, treat-to target trial assessing the effect of alirocumab versus placebo in 18,924 patients who had an ACS 1–12 months (median 2.6 months) before randomisation.^5,7

The trial targeted LDL-C to a range of 0.6–1.3 mmol/L and met its primary MACE [major adverse cardiovascular events] endpoint of a 15% relative risk reduction in the overall trial population.^5,7

Adverse events were similar between groups except for injection site reactions (alirocumab 3.8%, placebo 2.1%).^5,7

References

1. 2019 ESC/EAS Guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk: The TaskForce for the management of dyslipidaemias of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS). European Heart Journal, ehz455, https://doi.org/10.1093/eurheartj/ehz455
2. Aylward, P. 2019. Time to lower LDL cholesterol targets after cardiac events. Available at https://insightplus.mja.com.au/2019/43/time-to-lower-ldl-cholesterol-targets-after-cardiac-events/. [Last accessed November 4, 2019].
3. National Heart Foundation Australia. Cardiac Society of Australia and New Zealand. 2012. Reducing risk in heart disease. An expert guide to clinical practice for secondary prevention of coronary heart disease - summary. https://www.heartfoundation.org.au/images/uploads/publications/Reducing-risk-in-heart-disease.pdf
4. Ference, B.A. et al. 2017. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J 2017 38 2459 2472 https://doi.org/10.1093/eurheartj/ehx144
5. Schwartz, G.G., et al., Alirocumab and Cardiovascular Outcomes after Acute Coronary Syndrome. New England Journal of Medicine, 2018. 379(22): p. 2097-2107. https://doi.org/10.1056/NEJMoa1801174
6. Sabatine, M.S., et al., Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. New England Journal of Medicine, 2017. 376(18): p. 1713-1722 https://doi.org/10.1056/NEJMoa1615664
7. Praluent Approved Product Information - October, 2019. Available from http://www.guildlink.com.au/gc/ws/sw/pi.cfm?product=swppralu
    

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