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How Applicable is the 2025 Focused Update of the 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias to the Asia-Pacific Region?

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Disclosure: KCBT has received honoraria for lectures from Amgen, AstraZeneca, Bayer, Boehringer Ingelheim and Sanofi; and advisory board fees from Daiichi Sankyo and Eli Lilly

Correspondence: Kathryn Tan, Department of Medicine, University of Hong Kong, Queen Mary Hospital, Pokfulam Rd, Hong Kong. E: kcbtan@hku.hk

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© The Author(s). This work is open access and is licensed under CC-BY-NC 4.0. Users may copy, redistribute and make derivative works for non-commercial purposes, provided the original work is cited correctly.

A focused update of the 2019 European Society of Cardiology (ESC)/European Atherosclerosis Society (EAS) guidelines for the management of dyslipidaemias was recently presented at the ESC 2025 congress.1 New and revised recommendations in the update have been formulated based on novel evidence from major randomised controlled trials and meta-analyses published since the release of the 2019 ESC/EAS dyslipidaemia guidelines.2

Key changes in the update include an improvement in cardiovascular risk assessment by replacing the previous SCORE algorithm with the SCORE2 and SCORE2-OP algorithms. These newer versions of SCORE provide a more comprehensive cardiovascular risk evaluation, extend age up to 89 years and predict both fatal and non-fatal events.3,4

There are also new recommendations on the use of risk modifiers to refine and personalise risk determination, particularly in individuals at moderate risk or around treatment decision thresholds. These risk modifiers include the presence of subclinical atherosclerosis by imaging or increased coronary artery calcium score. Demographic factors, clinical conditions and selected biomarkers can also serve as risk modifiers. Another major cardiovascular risk-enhancing factor is elevated lipoprotein(a) (Lp(a)) levels >105 nmol/l.

In terms of treatment, LDL cholesterol (LDL-C) targets continue to be determined by a person’s level of risk. The update reaffirms very low LDL-C targets, particularly for patients at very high or extreme cardiovascular risk with recurrent vascular events.

The update reinforces the importance of a healthy lifestyle and recommends against the use of dietary supplements or vitamins for lowering LDL-C owing to a lack of evidence on their safety and effectiveness.

Beyond statin use, the update provides guidance on the use of newer therapies. Recommendations include the use of bempedoic acid in statin-intolerant patients and evinacumab for patients with homozygous familial hypercholesterolaemia.

For triglyceride-lowering therapies, only icosapent ethyl is recommended for the treatment of high-risk individuals with moderate hypertriglyceridaemia to reduce the risk of cardiovascular events, and volanesorsen for patients with familial hyperchylomicronaemia syndrome to prevent pancreatitis.

The role of combination therapies has been highlighted, and the update endorses the use of a combination of lipid-lowering agents with proven cardiovascular benefits for patients who cannot achieve their LDL-C goals with statins alone. The choice of medications depends on the degree of LDL-C lowering required, patient preference, availability and cost.

Furthermore, the update emphasises the importance of early, intensive lipid-lowering therapy in patients with acute coronary syndrome during their index hospitalisation. A combination of a statin with one or more classes of non-statin therapy is required up front in many of these high-risk individuals to achieve their LDL-C targets instead of using a stepwise approach.

Treatment of special populations has also been discussed, and the update recommends the use of statin therapy for people with HIV infection and for patients with cancer at a high risk of developing chemotherapy-related heart damage.

This latest focused update from the ESC/EAS on the management of dyslipidaemia is timely as the Global Burden of Disease Study has reported that ischaemic heart disease and stroke remained the leading cause of mortality in 2023.5 High LDL-C was the third largest contributor to the burden of ischaemic heart disease and ischaemic stroke globally and accounted for 20.8% of cardiovascular disease disability-adjusted life years. In the Asia-Pacific (APAC) region, there were large variations in cardiovascular disease burden and risk factors. The age-standardised cardiovascular disease disability-adjusted life year rates attributable to high LDL-C were high (>1,100 per 100,000) in the Pacific Islands and in South and Southeast Asia, and lower in high-income countries such as Japan and Australia (<520 per 100,000) in 2023.6

So what are the implications of this focused update for the APAC region? The update introduces a more comprehensive and precise approach to managing dyslipidaemia and cardiovascular risk. Several Asian countries have developed their own national guidelines and cardiovascular risk scores for the assessment and management of dyslipidaemia. Although there are some differences in recommendations, the main principles of these guidelines are the same as those set out by the ESC/EAS. The LDL-C targets in the guidance from India are very similar to those in the ESC/EAS focused update, whereas guidelines from China and Japan tend to be more conservative in their LDL-C targets.7–9

For cardiovascular risk assessment, risk scores developed primarily from western populations do not accurately reflect the cardiovascular risk in all Asian ethnicities. Locally derived native risk prediction models are not widely available and only a few Asian countries, such as China, Japan and Korea, have developed original risk models derived from their own population data. Many countries in the APAC region use either the Framingham or the WHO cardiovascular disease risk models, with or without recalibration.10

The SCORE2 algorithms have been systematically recalibrated by the SCORE2 Asia-Pacific writing group et al. for the APAC region, taking into account regional differences in cardiovascular disease incidence and risk profiles.11 APAC countries were grouped into four geographical cardiovascular risk regions, and the SCORE2 APAC model was recalibrated to predict the 10-year cardiovascular disease risk in individuals without diabetes or cardiovascular disease in the four risk regions. The use of the recalibrated SCORE2 APAC algorithms can help improve the identification of high-risk individuals and enable more personalised treatment strategies, particularly in low- and middle-income countries where there is a paucity of local epidemiological data and local risk models are lacking. Although the SCORE2 APAC model has been externally validated, the performance of the model should be compared with country-specific native cardiovascular prediction models, such as China-PAR and the Japanese Hisayama risk score, in their respective countries.

The recommended use of additional risk enhancers, such as coronary artery calcium score and Lp(a) to further refine risk estimation in individuals at moderate cardiovascular risk or at treatment thresholds, poses a major challenge in practice in the APAC region. Quantification of coronary artery calcium score and Lp(a) is available, but access, cost and clinical adoption vary by country. Recent data from the SingHEART study have demonstrated the utility of coronary artery calcium score as a risk-enhancing factor in asymptomatic Asian populations.12

In high-income countries, reimbursement for a coronary artery calcium scan is more likely if the test is performed for a diagnostic purpose. Most countries require out-of-pocket payment if a coronary artery calcium scan is used for the purpose of preventive screening. High Lp(a) levels pose cardiovascular risk across all ethnicities but awareness is low in the region.13 Lp(a) testing is available mainly in developed APAC countries such as Australia, New Zealand, Singapore, Japan and South Korea, but is not always reimbursed by national insurers. In other parts of APAC, the availability of Lp(a) testing is limited and the cost often prohibitive.

Statin therapy continues to remain the cornerstone of lipid management and the updated guidelines encourage the use of combination lipid-lowering therapy if required, depending on the desired magnitude of LDL-C reduction. Non-statin therapies with proven cardiovascular benefit, such as ezetimibe, proprotein convertase subtilisin/kexin type 9 monoclonal antibodies or bempedoic acid, can be used in patients who are unable to take statins or combined with maximum tolerated statin doses in patients who cannot achieve their LDL-C targets.

In the APAC region, statins are still under-prescribed and their use rate is significantly lower in Asian countries compared with the global average (16.1 defined daily doses per 1,000 population ≥40 years/day in South Asia versus 279.1 in North America in 2020).14 Adherence to statins is also low and a pan-Asian survey-based study showed that up to 44% of subjects acknowledged missing their statin medication.15 Hence, more needs to be done to improve the uptake of statin therapy.16

There has also been some reluctance to use high-intensity statins in Asians because of the increased risk of off-target effects, with higher statin doses having pharmacogenomic differences from Caucasians.17 Therefore, the new recommendation on combination therapy provides an alternative to high-intensity statins and may help to overcome therapeutic inertia to intensify treatment. For instance, the combination of ezetimibe with a moderate-intensity statin has been shown to be non-inferior to high-intensity statin monotherapy in preventing cardiovascular events in Asians.18

Although the therapeutic arsenal of lipid-lowering agents has expanded, the high cost of some of the newer agents significantly impacts health equity. Availability and affordability are major issues, particularly for the low- and middle-income countries in the APAC region.

Conclusion

The 2025 focused update of the 2019 ESC/EAS guidelines provides a strong, evidence-based contemporary framework for managing dyslipidaemia, especially for countries where local guidelines are lacking or outdated. Adaptation within local contexts is necessary given the heterogeneity in demographic and clinical characteristics of Asian populations.

The implementation of these consensus recommendations will be influenced by the accessibility and cost of the newer drugs and interventions. To what extent these recommendations can be applied will be determined by individual countries’ healthcare resources, accepted standards of care plus socioeconomic and cultural factors.

The establishment of large, contemporary and representative cohorts and collection of high-quality data on cardiovascular risk factors and incidence in the region are very much needed to facilitate the formulation of a regional APAC guideline.

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