Table of Contents
Year : 2020  |  Volume : 5  |  Issue : 3  |  Page : 130-138

Expert consensus on clinical pathway of blood lipid management in patients with acute coronary syndrome

Date of Submission01-Aug-2020
Date of Acceptance09-Sep-2020
Date of Web Publication30-Sep-2020

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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/cp.cp_20_20

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Recently, the burden of coronary events in patients with acute coronary syndrome (ACS) has increased with a high recurrence rate and mortality. The management of blood lipid levels in patients with ACS is challenging under the current treatment mode. Based on practice experience of domestic specialists and the reference of international clinical practice, together with the evidence of lipid lowering in patients with ACS, this expert consensus proposes suggestions targeting lipid-lowering interventions, commonly used lipid-lowering drugs, and the clinical pathway of lipid management in patients with ACS. This work aims to standardize the lipid management and reduce the recurrence risk of cardiovascular events in patients with ACS.

Keywords: Acute coronary syndrome; Clinical pathway; Low-density lipoprotein-cholesterol

How to cite this article:
Chinese Medical Doctor Association, Expert Group of Clinical Pathway of Lipid Management in Patients with Acute Coronary Syndrome. Expert consensus on clinical pathway of blood lipid management in patients with acute coronary syndrome. Cardiol Plus 2020;5:130-8

How to cite this URL:
Chinese Medical Doctor Association, Expert Group of Clinical Pathway of Lipid Management in Patients with Acute Coronary Syndrome. Expert consensus on clinical pathway of blood lipid management in patients with acute coronary syndrome. Cardiol Plus [serial online] 2020 [cited 2021 May 9];5:130-8. Available from:

  Introduction Top

Acute coronary syndrome (ACS) refers to acute myocardial ischemia syndrome caused by the rupture or erosion of unstable atherosclerotic plaque in the coronary artery and the formation of fresh thrombus, including ST-segment elevation myocardial infarction and non-ST elevation (NSTE) myocardial infarction, and unstable angina pectoris.[1] Patients with ACS face risks associated with the use of anticoagulants in the acute phase, antiplatelet, and revascularization therapy. The management of risk factors, especially high cholesterol, plays an important role in the management of blood lipids. Under the current treatment strategy, the management of blood lipid levels in patients with ACS remains challenging. Patients with ACS belong to the extremely high-risk population,[2] and the recurrence and mortality rates of coronary events are high. The long-term follow-up study of patients with ACS (EPICOR-Asia Study) showed that the incidence of total coronary events 1 year after discharge was as high as 12.5% and the mortality within 2 years was 5.2%.[3],[4] A survey of 30-day mortality of hospitalized patients with acute myocardial infarction (AMI) in Beijing from 2007 to 2012 showed that the age-standardized mortality was 9.7%; the death of 77,943 in patients with AMI within 30 days was attributed to coronary heart disease (CHD).[5] The burden of ACS is increasing in China and has become a major public health concern.

Dyslipidemia is one of the most important risk factors for atherosclerosis.[6] However, the status of the blood lipid management in patients with ACS in China is not ideal because the compliance rate is <50%,[7],[8] and the risk of recurrent events is significantly increased. For patients with ACS and multiple coronary artery disease, multiple coronary events, diabetes mellitus (DM), and multivessel bed disease, the baseline risk is higher and therefore, it is necessary to reinforce the management of blood lipids. In recent years, evidence of basic and clinical research has further confirmed that low-density lipoprotein-cholesterol (LDL-C) is the primary intervention target for atherosclerotic cardiovascular disease (ASCVD), and the strategy becomes more practical and indisputable. At the same time, other blood lipid parameters, such as the lipoprotein a, Lp (a), have received increasing attention. Several studies showed that the Lp (a) level is an effective index to predict the risk of recurrent cardiovascular events in patients with CHD and is associated with the severity of coronary artery disease.[9],[10]

Evidence-based treatments of patients with ACS focused on lowering lipids have increased in recent years. New treatment methods and interventional strategies may further reduce the risk of recurrent events in these patients. Currently, it is difficult for clinicians to manage the blood lipid level outside the hospital, and reinforcing the management in the hospital setting may help improve the patients' compliance with treatment. To standardize the lipid management and reduce the recurrence risk of cardiovascular events in patients with ACS, the Chinese Medical Doctor Association produced this consensus based on the clinical status and clinical experience of specialists.

Target of lipid regulation intervention

Dyslipidemia, especially an increase in the LDL-C level in patients with ACS, is the key factor leading to the occurrence and development of cardiovascular disease (CVD). For the management of blood lipid levels in patients with ACS, the current guidelines unanimously emphasize that LDL-C is still the main target for lipid regulation intervention. Based on clinical evidence, the target value for the LDL-C level could be further reduced from the 1.8 mmol/L (70 mg/dL) reference value to <1.4 mmol/L (55 mg/dL), or the range of reduction in the lipid level could be increased.[11],[12] For patients with recurrent vascular events within 2 years (not necessarily the same as the first event) who take the maximum tolerated dose of statins, the target value for LDL-C levels could be considered <1.0 mmol/L (<40 mg/dL). The IMPROVE-IT study showed that the LDL-C level of patients with ACS treated with ezetimibe combined with simvastatin and simvastatin monotherapy decreased to 1.4 mmol/L (53.7 mg/dL) and 1.8 mmol/L (69.5 mg/dL), respectively, and the relative risk of major end point events in the simvastatin combined group decreased by 6.4%.[13] The ODYSSEY Outcomes study showed that the LDL-C level of patients with ACS treated with alirocumab could be reduced to 1.38 mmol/L (53.3 mg/dL). After 12 months of treatment, the LDL-C levels of patients treated with alirocumab were 61.0% and 54.7%, respectively, compared with those of patients treated with placebo. The primary end point events in the alirocumab group were reduced by 15%, and the all-cause mortality decreased by 15%; LDL-C levels were highly reduced to ≤0.39 mmol/L. A subgroup analysis showed that cardiovascular events were further reduced by 29% in patients with 0.38 mmol/L (15 mg/dL) without increasing the incidence of adverse reactions, such as new-onset diabetes, neurocognitive impairment, and hemorrhagic stroke.[11] The FOURIER study included patients with ASCVD (mostly patients with stable CHD) treated with evolocumab. At 48 weeks, the LDL-C level and Lp (a) level were reduced by 59% and 26.9%, respectively, and the major cardiovascular events were reduced by 15%.[12]

Lp (a) is a LDL that has recently attracted much attention. Pathophysiological, epidemiological, and genetic studies provide strong evidence for the causal relationship between Lp (a) levels and CVD.[14],[15] The subgroup data from the ODYSSEY Outcomes study showed that the decrease in Lp (a) level was statistically significantly correlated with the decrease in the risk for major adverse cardiovascular events (P = 0.0081).[16] The Lp (a) level was significantly skewed in the normal population. Although in some individuals, Lp (a) levels could be as high as 1000 mg/L (100 mg/dL) or more, 80% of normal individuals had levels below 200 mg/L (20 mg/dL).[17] There are racial differences in the Lp (a) population distribution, and the current threshold for cardiovascular risk prediction, 500 mg/L (50 mg/dL), is based on clinical data from Caucasians.[18] At present, the Lp (a) reference range and cardiovascular risk prediction threshold for the Chinese population have not been established. A multicenter, prospective cohort study conducted in China showed 4078 cases of percutaneous coronary intervention (PCI) in patients with stable CHD. During an average follow-up after 4.9 years, the Lp (a) levels <15, 15–30, and ≥30 mg/dL corresponded to 49.2%, 20.2%, and 30.6% of the total population, respectively. Elevated levels of Lp (a) increased by 30% and 29% of the cardiovascular events and risk of stroke, respectively. Patients with Lp (a) level ≥30 mg/dL (60 nmol/L) had significantly lower event-free survival rates than those with Lp (a) level <15 mg/dL (30 nmol/L). Further analysis showed that Lp (a) level ≥30 mg/dL (60 nmol/L) increased the risk of vascular events by 1.1 times compared to that in patients with Lp (a) level <15 mg/dL (30 nmol/L).[19]

Commonly used lipid-lowering drugs

The commonly used lipid-lowering drugs mainly include statins, cholesterol absorption inhibitors, and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors.


Statins competitively inhibit the activity of the 3-hydroxy-3-methylglutaryl CoA reductase, reduce cholesterol synthesis, upregulate the LDL receptor on the surface of hepatocytes, and accelerate the metabolism of serum LDL. The European and American guidelines recommend that all patients with ACS should start or continue to use high-dose statins as soon as possible.[20] However, because of ethnic differences in the metabolism of statins, Chinese individuals have higher sensitivity and poorer tolerance to statins than Europeans and Americans. The DYSIS-China study pointed out that compared with low- and medium-intensity statins, high-intensity statins are not favorable for compliance with LDL-C-lowering treatments, which may be related to the “6% Rule,” that is, doubling the dose of statins can only result in an additional 6% decrease in the LDL-C level.[21] The HPS2-THRIVE study showed that when using the same dose of statins at medium intensity, the increase in the rate of liver enzymes (>3 times of the upper limit of the normal value) in Chinese patients was ten times higher than that in European patients, and the risk of myopathy in Chinese patients was also ten times higher than that in European patients. In other words, the incidence of liver muscle adverse reactions in Chinese patients was significantly higher than that in European patients.[22] Therefore, Chinese guidelines for dyslipidemia recommend that moderate-intensity statins should be used in patients with ACS at the beginning of the treatment. The dosage should be adjusted according to the individual lipid-lowering efficacy and tolerance. If the cholesterol level cannot reach the target value, other lipid-regulating drugs, such as ezetimibe and PCSK9 inhibitors, may be considered.[17]

The effect of statins on the Lp (a) level is still controversial.[23],[24] The AFCAPS, CARDS, 4D, and LIPID studies have all shown that statins may reduce the level of Lp (a) by 1%, 13%, 6%, and 7%, respectively, but the JUPITER, MIRACL, and 4S studies showed that statins fail to reduce the level of Lp (a) by 2%, 9%, and 15%, respectively.[25] Data analysis of 1369 CHD patients treated with statins in China showed that long-term statin treatment (median 677 days) could significantly reduce Lp (a) levels in patients with CHD compared with short-(median 39 days) or medium-term (median 219 days) treatments, but the therapeutic effect was affected by traditional risk factors such as essential hypertension, diabetes, and LDL-C levels.[26] A retrospective analysis of 154 patients with ACS who underwent PCI showed that rosuvastatin and atorvastatin significantly reduced serum Lp (a) levels.[27] However, a recently published meta-analysis confirmed that statins significantly increased the level of Lp (a) (<0.0001) compared to that of placebo. Attention should be paid to the risk of CVD associated with elevated Lp (a) levels.[28]


Ezetimibe is an inhibitor of the cholesterol absorption that reduces the cholesterol level transported to the liver by inhibiting the absorption of cholesterol through the brush border of the intestine. Ezetimibe combined with statins may produce a desirable synergistic effect. A prospective randomized study conducted in China reported that patients with NSTE-ACS were administered lipid-lowering treatment consisting of ezetimibe combined with rosuvastatin within 24 h after PCI. At 12 weeks, the rate to reach the target LDL-C value (<1.81 mmol/L) was significantly higher than that in the medium- and high-dose rosuvastatin groups, and the incidence of drug-related adverse events was not increased.[29] The IMPROVE-IT study showed that ezetimibe combined with simvastatin could further reduce by 2.0% the absolute risk of cardiovascular events in patients with ACS.[13] However, the effect of ezetimibe on the Lp (a) level was not obvious. A meta-analysis of ten randomized, placebo-controlled, clinical trials showed that ezetimibe alone or combined with statins had no statistically significant effect on the Lp (a) level (P = 0.187 and P = 0.700, respectively).[30]

Proprotein convertase subtilisin/kexin Type 9 inhibitors

PCSK9 inhibitors specifically bind to PCSK9 and block its binding to the LDL-C receptor, thus clearing LDL-C and reducing its blood level.[31],[32] The clinical effects include a reduction in the serum LDL-C levels by at least 45%–60%, a 10%–15% reduction in the triglyceride (TG) levels, a 25%–30% reduction in the Lp (a) levels, and a 5%–10% increase in the high-density lipoprotein-cholesterol (HDL-C) levels.[32] A randomized controlled study confirmed that the difference between PCSK9 inhibitors combined with statins before and after treatment of LDL-C and Lp (a) was significantly higher than that of atorvastatin alone, therefore PCSK9 inhibitors effectively reduce blood lipid levels in very high-risk patients with ASCVD.[33] The BERSON clinical trial is a prespecified analysis of patients in the BERSON study in China. Patients initiated background atorvastatin 20 mg/day, after which they were randomized 2:2:1:1 to evolocumab 140 mg every 2 weeks (Q2W) or 420 mg monthly (QM) or to placebo Q2W or QM. Among 453 patients randomized in China, 451 received at least one dose of the study drug (evolocumab or placebo). Evolocumab significantly reduced LDL-C compared with placebo at week 12 (Q2W, −85.0%; QM, −74.8%) and at the mean of weeks 10 and 12 (Q2W, −80.4%; QM, −81.0%) (adjusted P<0.0001 for all) when administered with background atorvastatin. Non-HDL-C, ApoB100, total cholesterol, Lp (a), TGs, HDL-C, and very LDL-C significantly improved with evolocumab versus placebo. This study demonstrated that in patients in China with T2DM and hyperlipidemia or mixed dyslipidemia receiving background atorvastatin, evolocumab significantly reduced LDL-C and other atherogenic lipids, was well tolerated, and had no notable impact on glycemic measures.[34] The worldwide approved PCSK9 inhibitors are alirocumab and evolocumab. The prescription of these drugs for the prevention of cardiovascular events was approved based on the ODYSSEY Outcomes and the FOURIER studies. Compared with patients in the FOURIER study, those in the ODYSSEY Outcomes study had higher cardiovascular risk (patients with ACS were enrolled in the ODYSSEY Outcomes study, and patients with ASCVD, mostly those with stable CHD, were enrolled in the FOURIER study). In the case of patients with ACS, evidence-based results show that alirocumab has a stronger effect that that of evolocumab. The ODYSSEY Outcomes study suggested that treatment with statins in combination with PCSK9 inhibitors for at least 4 months could result in a sustained and stable decrease in the LDL-C level by at least 50%, whereas the continuous use of statins for >1 year could show a downward trend in cardiovascular adverse events. A meta-analysis of the efficacy and safety of alirocumab and evolocumab showed that the group treated with alirocumab was associated with a decrease in the all-cause mortality (0.81/100 person-years vs. 1.01/100 person-years; P = 0.008) compared to that of the placebo-treated control. Even if data from the ODYSSEY Outcomes study were excluded, there is still a trend showing that the treatment with alirocumab is associated with a decrease in the all-cause mortality (0.37/100 person-years vs. 0.68/100 person-years; P = 0.06).[35]

Other lipid-lowering drugs

Nonstatin lipid-lowering drugs include those that reduce the LDL-C level, such as the cholic acid chelator; those that reduce TGs, such as beta and nicotinic acid; and other lipid-lowering drugs, such as omega-3 fatty acids. In addition, for patients with ACS, familial hypercholesterolemia, and other special conditions, it is often necessary to combine multiple drugs to achieve the target LDL-C value.

  Clinical Pathway for Lipid Management Top

Patients with ACS are in urgent need of intensive lipid management; therefore, this consensus only articulates a lipid management path for such patients. For patients without high-risk factors, the lipid management may be modified based on this pathway and according to the target value of lipid reduction. The clinical pathway of lipid management is shown in [Figure 1].
Figure 1: Clinical pathway of lipid management in patients with ACS with high-risk factors: (1) If the patients are intolerant to statins, the use of nonstatin lipid-lowering drugs directly is recommended. (2) Based on the evidence in recent patients with ACS, priority is given to the use of alirocumab. (3) In order to avoid the rebound of the lipid-lowering effect, consider drug withdrawal according to the range of each drug to reduce LDL-C. (4) After combined lipid-lowering drug treatment, LDL-C level has not reached the target level, especially if the disease is in progress. In addition, we suggest that the use of lipoprotein plasma exchange as an adjuvant therapy should be considered.[36] Note: ACS: Acute coronary syndrome, LDL-C: Low-density lipoprotein-cholesterol, PCSK9: Proprotein-converting enzyme subtilisin 9

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Writers: Zhang Feng (Sun Yat Sen Hospital Affiliated to Fudan University) and Jin Qinhua (PLA General Hospital)

Expert group members (sorted by first letter of surname)

Bu Jun (Renji Hospital affiliated to the Medical College of the Shanghai Jiaotong University), Chen Jiyan (Guangdong Provincial People's Hospital), Chen Yundai (General Hospital of the Chinese People's Liberation Army), Chen Zhenyue (Ruijin Hospital affiliated to the Shanghai Second Medical University), Cong Hongliang (Tianjin Chest Hospital), Du Zhimin (The First Affiliated Hospital of the Sun Yat Sen University), Fu Guosheng (Sir Run Run Shaw Hospital affiliated to the Zhejiang University), Fu Naikuan (Tianjin Chest Hospital), Gao Wei (Peking University Third Hospital), Ge Junbo (Zhongshan Hospital affiliated to the Fudan University), Han Bing (Xuzhou Fourth People's Hospital) He Ben (Chest Hospital affiliated to the Shanghai Jiaotong University), Hou Yuqing (Southern Hospital of the Southern Medical University), Huang Rong-Chong (Beijing Friendship Hospital affiliated to the Capital Medical University), Huo Yong (Peking University First Hospital), Jiang Jun (Second Affiliated Hospital of the Zhejiang University School of Medicine), Jin Qinhua (General Hospital of the Chinese people's Liberation Army), Kong Xiangqing (Jiangsu Provincial People's Hospital), Li Xiaodong (Shengjing Hospital affiliated to the China Medical University), Li Yi (The First Affiliated Hospital of the Sun Yat Sen University), Lin Wenhua (TEDA International Cardiovascular Hospital) Liu Jian (People's Hospital of the Peking University), Ma Genshan (Zhongda Hospital affiliated to the Southeast University), Peng Daoquan (Second Xiangya Hospital of the Central South University Changsha), Qian Juying (Zhongshan Hospital affiliated to the Fudan University), Song Xiantao (Beijing Anzhen Hospital affiliated to the Capital Medical University), Wang Jian'an (Second Affiliated Hospital of the Zhejiang University Medical College), Xiang Dingcheng (Southern General Hospital of PLA), Xu Biao (Drum Tower Hospital affiliated to the Medical College of Nanjing University), Xu Yawei (Shanghai Tenth People's Hospital), Yang Jiefu (Beijing Hospital), Yang Qing (General Hospital of the Tianjin Medical University), Yang Xinchun (Beijing Chaoyang Hospital affiliated to the Capital Medical University), Yao Qiheng (University of Hong Kong-Shenzhen Hospital), Zhang Daqing (Shengjing Hospital affiliated to the China Medical University), Zhang Feng (Zhongshan Hospital affiliated to the Fudan University), Zheng Jingang (Sino-Japanese Friendship Hospital), and Zhou Yujie (Beijing Anzhen Hospital affiliated to the Capital Medical University).
Table 1: Cardiovascular risk stratification and low density lipoprotein-cholesterol treatment goals in patients with acute coronary syndrome

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Table 2: Reduction in low-density lipoprotein-cholesterol levels using different lipid-lowering strategies[6],[16]

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Table 3: Cholesterol-lowering intensity of statins[6]

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Financial support and sponsorship


Conflicts of interest

During the revision of this consensus, Sanofi (China) Investment Co., Ltd. supported the revision meeting but did not participate in or influence the academic content and evidence evaluation of the consensus, and the consensus remained independent.

  Appendix 1 Top

  • Patient education: Lack of long-term knowledge of lipid management in patients with acute coronary syndrome (ACS) is the main reason for their low blood lipid levels and poor compliance with treatment. It is particularly necessary to provide health education for patients and/or caregivers, help patients change unhealthy lifestyles, and implement measures for secondary prevention. Patient education and cardiac rehabilitation based on evidence-based medicine should be conducted throughout the treatment period and may be arranged regularly or individually according to the need to solve problems
  • In-hospital rehabilitation period: The best time for patient education is at admission; this would help patients have a full understanding of the disease, reduce their fears, and emphasize the importance of controlling risk factors. Second, the patients at moderate and high risk should be identified, the risk factors of coronary heart disease should be evaluated, and the corresponding intervention plan should be formulated. It is necessary to organize patient education meetings in the hospital to let patients and/or caregivers understand the severity and prognosis of the diseases and inform patients and/or caregivers of the importance of blood lipid management, especially the clinical significance of reducing the low-density lipoprotein-cholesterol(LDL-C) level rapidly and substantially to improve their self-management awareness and enthusiasm
  • All lipid-lowering drugs, such as statins, ezetimibe, and proprotein convertase subtilisin/kexin type9(PCSK9) inhibitors, should be introduced before the treatment. If the economic situation of the patients is good, PCSK9 inhibitors combined with statins may be recommended for the initial treatment, especially for patients at high risk of ACS who need percutaneous coronary intervention or patients with familial hypercholesterolemia, diabetes, multivessel disease, or previous cardiovascular history
  • At discharge: It is important to conduct positive psychological education to inform patients that they need to actively control risk factors, such as smoking and lipid levels. Once discharged from the hospital, patients may be followed up and registered on a digital platform, a follow-up plan is made, and the time of the follow-up visit is informed to the patient. Patients using lipid-lowering drugs should be informed of the need of the long-term use and the importance of adhering to the treatment. Patients should be informed of the correct use of lipid-lowering drugs, including drug usage, dosage, adverse drug reactions, and medication precautions. For patients who use PCSK9 inhibitors, we provide injection guidance, inform patients of injection-related precautions, and remind patients of regular injection time
  • Out-of-hospital rehabilitation period: The purpose of the follow-up examination is for the patient to understand the control of the disease over time and emphasize lifestyle changes as the basis of lipid intervention. To prevent the recurrence of cardiovascular events, we should articulate reasonable lipid-lowering strategies. The patients are followed up every 4–6weeks; after that, if there are no special cases and the blood lipid level is in the standard range, the patients may be followed up every 6–12 months; after discharge, patients are followed up once a year. The follow-up examination mainly includes blood lipid, liver function, and creatine kinase tests. Based on the blood lipid levels, it may be necessary to explain to the patient the adjustments of the treatment regimen. Especially for patients whose LDL-C level is not in the? standard range after treatment with moderate-intensity statins, treatment with a combination of PCSK9 inhibitors may be recommended. If the type or dose of lipid-lowering drugs is adjusted, the patients should be reexamined within 4–6weeks of treatment, and the treatment regimen should be adjusted again depending on whether the target value was achieved or not. It is important to reinforce the psychological education of patients and their families to improve the long-term medication compliance and inform the patients about the time of follow-up visit and relevant precautions.


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  [Figure 1]

  [Table 1], [Table 2], [Table 3]


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