2025 Consensus on the Clinical Pathway of Blood Cholesterol Management in Taiwan

Abstract

Increased low-density lipoprotein cholesterol (LDL-C) is one of the most important risk factors for atherosclerotic cardiovascular disease (ASCVD). However, the attainment rate of recommended LDL-C targets is not optimal with significant scope for improvement in Taiwan. This clinical pathway for cholesterol management was developed based on the Taiwan lipid guidelines and expert opinions from major medical societies in Taiwan. It was designed with the aim of improving the outcomes of people at risk of or with ASCVD who would benefit from lipid control to reduce the risk of new or recurrent cardiac events. The pathway proposes adequate LDL-C targets for people at different risk levels of ASCVD and standardizes lipid management and follow-up in patients receiving lipid lowering therapy. The ultimate purpose is to facilitate the attainment of individual LDL-C targets and ensure that patients are monitored adequately and optimized on the appropriate lipid lowering therapy to reduce the risk of ASCVD.

Abbreviations

ASCVD, Atherosclerotic cardiovascular disease

CKD, Chronic kidney disease

CV, Cardiovascular

LDL-C, Low-density lipoprotein cholesterol

LLT, Lipid-lowering therapies

non-HDL-C, Non-high-density lipoprotein cholesterol

INTRODUCTION

Cardiovascular (CV) disease is the second leading cause of death in Taiwan, and atherosclerotic cardiovascular disease (ASCVD), including coronary heart disease, cerebrovascular disease, peripheral artery disease and aortic atherosclerotic disease, is the major cause of CV death. ASCVD mortality has progressively increased over the past decade in Taiwan.¹ An elevated low-density lipoprotein cholesterol (LDL-C) level has been identified as a significant risk factor contributing to ASCVD. The Cholesterol Treatment Trialists meta-analysis found that every 1 mmol/L (38.7 mg/dL) decrease in LDL-C achieved through lipid-lowering therapy (LLT) over a span of five years was associated with a 22% reduction in major CV events, a 20% decrease in coronary death, and a 10% reduction in all-cause mortality.² In addition, the benefits of intensive LDL-C control have been shown to accumulate, so that a larger absolute benefit can be achieved with a longer duration of LLT, highlighting the importance of consistently maintaining an adequate LDL-C level.³

The objective of this consensus was to bridge the gaps in implementing guideline-recommended practice by developing a nationwide lipid clinical pathway to ensure comprehensive and consistent ASCVD care in Taiwan. The clinical pathway was developed based on the recommendations from the previously published Taiwan lipid guidelines^4-6 and expert opinions from nine major medical societies in Taiwan, including the Taiwan Society of Cardiology, Taiwan Society of Lipids and Atherosclerosis, Taiwan Society of Cardiovascular Interventions, Taiwan Society of Internal Medicine, Taiwan Stroke Society, Taiwan Association of Family Medicine, Taiwan Diabetes Association, Taiwanese Association of Diabetes Educators, and Taiwan Society of Nephrology. The clinical pathway establishes a fundamental standard for physicians to uniformly adopt in their clinical practice across all levels of medical institutions in Taiwan. By incorporating risk stratification, comprehensive assessments, goal-oriented management, and enhanced follow-up, the aim of the pathway is to effectively optimize early ASCVD prevention and ultimately enhance patient outcomes on a broader scale.

RISK STRATIFICATION

The importance of lowering LDL-C to prevent ASCVD has been emphasized in previous Taiwan lipid guidelines.^4-6 In order to achieve CV risk reduction, it is essential to set specific treatment goals tailored to the individual needs of the patient. The first step of the clinical pathway is to stratify the risk of ASCVD for an individual and recommend a goal-oriented treatment approach based on their risk level. This approach can improve patient-physician communication regarding clear LDL-C goals and enhance treatment adherence.

Table 1 summarizes the criteria used for risk stratification. There are five risk categories: low, moderate, high, very high, and extremely high. Subjects at low, moderate and high risk refer to those with primary prevention. For primary prevention in individuals without confirmed ASCVD, high-risk groups indicate those with diabetes, chronic kidney disease (CKD) or severe hypercholesterolemia with LDL-C ≥ 190 mg/dL. In addition, for patients who undergo computed tomography, depending on access and the need for such examinations, those with a coronary artery calcium score ≥ 400 should be categorized as high risk.⁷ Moderate and low risk indicate subjects without factors considered to indicate high risk but with other risk factors. Moderate risk indicates those with two or more risk factors, and low risk indicates those with one risk factor. Those at very high and extremely high risk indicate secondary prevention with clinically confirmed ASCVD (Table 1). The recommended LDL-C target values are < 130 mg/dL, < 115 mg/dL, < 100 mg/dL, < 70 mg/dL, and < 55 mg/dL for those at low, moderate, high, very high, and extremely high risk, respectively. In addition to LDL-C, it is also important to control hypertension and diabetes. The goal for blood pressure is < 130/80 mmHg, and the goal for blood sugar is an HbA1c level < 7%.

CLINICAL PATHWAY

Figure 1 summarizes the clinical pathway for primary prevention. Early screening is recommended for the presence of high-risk conditions including diabetes, CKD and hypercholesterolemia (LDL-C ≥ 190 mg/dL) during routine adult health check-ups. For those with severe hypercholesterolemia, the diagnostic criteria of familial hypercholesterolemia should be used to identify potential cases, and genetic testing may be considered for confirmation.⁴ High-risk individuals should receive prompt LLT and lifestyle modifications. For those not considered to be at high risk, further evaluation depends on the presence of other CV risk factors. Individuals at low to moderate risk are recommended to engage in a 3 to 6-month period of lifestyle modifications, including healthy diet, regular exercise, smoking cessation, and weight control. If adequate LDL-C targets are not achieved, long-term LLT can be considered after shared decision-making, because patient adherence to treatment is important for LDL-C control (Figure 1).

Figure 1.

Clinical pathway for primary prevention. ATP, adenosine triphosphate; BP, blood pressure; CKD, chronic kidney disease; CV, cardiovascular; DM, diabetes mellitus; HbA1c, hemoglobin A1c; LDL-C, low-density lipoprotein cholesterol; PCSK9 mAb, proprotein convertase subtilisin/kexin type 9 monoclonal antibody.

Figure 2 summarizes the clinical pathway for secondary prevention. For patients with clinical ASCVD or imaging evidence of significant atherosclerotic plaque burden with ≥ 50% diameter stenosis, intensive immediate LLT is necessary. The choice of initial LLT should consider the expected reduction in LDL-C level, previous medication history, and the patient’s clinical condition. The early combination of non-statin medications can be considered if clinical judgement determines that the desired LDL-C treatment goal cannot be attained through statin therapy alone (Figure 2).

Figure 2.

Clinical pathway for secondary prevention. Abbreviations of Figure 1 and 2 are the same.

MANAGEMENT AND MONITORING

The lipid profile should be re-assessed at 6-8 weeks after initiating statin treatment to evaluate whether the recommended LDL-C treatment goal has been achieved (Figures 1 and 2). If the LDL-C target has not been achieved, statin treatment can be titrated to high intensity or the maximally tolerated dose. Adding on non-statin medications can also be considered, including ezetimibe, monoclonal antibodies or siRNA of proprotein convertase subtilisin/kexin type 9, and adenosine triphosphate citrate lyase inhibitor. Non-statin medications are also options for patients who cannot tolerate statins or have concerns of harmful drug-drug interactions with statins. The LDL-C level should be monitored again within 1 to 3 months after modifying the treatment until the treatment goal is attained. After achieving the treatment goal, it is recommended to monitor the lipid profile every 6 months in patients at high risk or above. For those with low to moderate risk, monitoring their lipid profile every 6 to 12 months is feasible depending on their clinical condition. Liver function should be measured within 3 months of starting statin treatment or any additional up-titration of the statin dose, but there is no need for repeated testing unless clinically indicated.

Adherence to treatment plays a crucial role in maintaining consistent LDL-C control and improving CV outcomes. Incorporating strategies that improve adherence into the clinical pathway is recommended, including: (1) communicating the LDL-C goal to the patients when initiating an intervention, (2) using digital tools such as the Taiwan National Health Insurance app (My Health Bank) to enhance self-care ability, and (3) delivering patient education or using an engagement kit. The efficacy of LLT should be re-assessed at follow-up to confirm patient response and adherence to therapies.

OTHER LIPID TARGETS

This consensus emphasizes the use of LDL-C as the primary therapeutic target and as a measure of long-term lipid control. Non-high-density lipoprotein cholesterol (non-HDL-C) can be considered as a secondary target in lipid management when an optimal LDL-C level has been achieved. Non-HDL-C is calculated as total cholesterol – HDL-C and is particularly useful for further CV risk assessment in patients with high triglycerides, diabetes, and obesity. The treatment target for non-HDL-C should be 30 mg/dL higher than the LDL-C value. Therefore, the treatment goals for those with a low to extremely high-risk level are < 160, < 145, < 130, < 100, and < 85 mg/dL, respectively. Other lipid parameters such as apoB and lipoprotein (a) have also been shown to have independent predictive value for CV risk and can be considered for lipid management based on the patient’s clinical condition and feasibility of testing.

SUMMARY

This clinical pathway is based on guidelines and expert opinion, and aims to standardize cholesterol management in Taiwan. The ultimate purpose is to reduce ASCVD risk and enhance patient outcomes through its implementation.

DECLARATION OF CONFLICT OF INTEREST

All the authors declare no conflict of interest.