New ESC/EAS dyslipidemia guidelines advocate “lower is better” for LDL-c

ESC 2019 The guidelines emphasize that the absolute LDL-C reduction drives the clinical benefit. Evidence suggests a benefit of treating earlier, which may mean less intensive therapy in the longer-term.

Presented at ESC Congress 2019 in Paris, France

LDL-c levels should be lowered as much as possible to prevent cardiovascular disease, especially in high and very high risk patients. That is one of the main messages of the European Society of Cardiology (ESC) and European Atherosclerosis Society (EAS) Guidelines on dyslipidaemias, presented at the ESC congress in Paris, France. The guidelines are an update to the 2016 ESC/EAS Dyslipidemia guidelines. Since then, major clinical trials have demonstrated the efficacy of PCSK9 inhibiting therapy in lowering LDL-c levels beyond those attained on intensive statin treatment. This results in significant reduction in CV events in patients with established atherosclerotic CV disease and acute coronary syndrome (ACS). There is no lower limit of LDL-c that is known to be unsafe. The guidelines aim to ensure that the available drugs (statins, ezetimibe, PCSK9 inhibitors) are used as effectively as possible to lower levels in those most at risk.

Additionally, there has been further information from the IMPROVE-IT trial with ezetimibe, which demonstrated enhanced absolute CV benefit in very high-risk individuals with diabetes compared with those without, reflecting the higher absolute risk of this group.

Moreover, knowledge of the impact of genetic variants influencing LDL-C levels and lifelong risk for ischaemic heart disease has increased, driven largely by insights from Mendelian randomisation studies.

New recommendations in these guidelines, compared to the 2016 version, include:

• LDL-c levels should be lowered as much as possible to prevent CV disease, especially in high (<70 mg/dL or<1.8 mmol/L and at least 50% reduction from baseline) and very high-risk patients (in both primary and secondary prevention, patients should achieve both a goal of <55 mg/dL or <1.4 mmol/L and at least 50% reduction from baseline).
• Revisions have been made to the risk stratification categories so that patients with ASCVD, diabetes with target organ damage, familial hypercholesterolaemia, and severe chronic kidney disease are all categorised as very high-risk. ACS patients are now also considered to be at very high risk of recurrent events.
• The guidelines emphasize the importance of combination therapy, first with ezetimibe and followed by a PCSK9 inhibitor to achieve the recommended targets in high-risk patients.
• While statin treatment remains the first choice for managing high triglycerides (TG, >200 mg/dL or 2.3 mmol/L), the new guidelines have taken account of evidence from REDUCE-IT and recommend n-3 PUFAs (particularly icosapent ethyl 2 x 2 g daily) in high-risk patients with persistently elevated TG (between 135 - 499 mg/dL or 1.5 and 5.6 mmol/L) despite statin treatment. In high-risk patients at LDL-C goal with TG >200 mg/dL or >2.3 mmol/L, fenofibrate or bezafibrate may be considered in combination with statins.
• Considering new insights from epidemiological and Mendelian randomisation studies that Lp(a) is causal in ischemic heart disease, the guidelines now recommend Lp(a) at least once in adults. Current options for treatment of high Lp(a) are limited to the PCSK9 inhibitors which have been shown to reduce levels by 25-30% on average with or without background statin therapy.
• Assessment of arterial (carotid and/or femoral) plaque burden on arterial ultrasonography, and CAC score assessment with CT should be considered as a risk modifier in individuals at low to moderate risk.
• Treatment with statins is recommended for primary prevention, according to the level of risk, in older people aged ≤75. The evidence for statin therapy is more limited in patients over 75, though is still consistent with a benefit. The guidelines advise taking level of risk, baseline LDL-c, health status, and the risk of drug interactions into account when deciding whether statins are appropriate in those aged 75 or over.
• Statin therapy is not recommended in pre-menopausal patients with DM who are considering pregnancy or not using adequate contraception.

In conclusion, these new ESC/EAS dyslipidaemia guidelines emphasise that lower LDL-c is better; the absolute LDL-c reduction drives the clinical benefit. Evidence from Mendelian randomisation studies has been critical in driving a ‘sea change’ to treat earlier, which ultimately may mean less intensive therapy in the longer-term. With the new LDL-c goals comes recognition of the importance of combination therapy in high and very high-risk patients, first with ezetimibe and then a PCSK9 inhibitor, to attain these levels. The fundamental next steps are appropriate implementation by clinicians in their practice, together with ensuring treatment adherence by patients.

- Our reporting is based on the information provided at the ESC congress -

The new ESC/EAS dyslipidaemia guidelines were simultaneously published in Eur Heart J Watch our video about the new dyslipidemia guidelines