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Huo Yong, Ge Junbo, Han Yaling, Wang Jianan, Wan Zheng, Li Jianping, Qian Juying, Wang Bin, Xiang Meixiang and Sun Yuemin. Expert Consensus on Intensive Statin Therapy for Patients with Acute Coronary Syndrome. Cardiology Plus 《门诊》获授权转载 On behalf of the expert group of Expert Consensus on Intensive Statin Therapy for Patients with Acute Coronary Syndrome. Acute coronary syndrome; Intensive statin therapy; Expert consensus I. Necessity for the Consensus1. Acute coronary syndrome and statins: Acute coronary syndrome (ACS) refers to a group of clinical conditions characterized by acute myocardial ischemia, including unstable angina (UA), non-ST-segment elevation myocardial infarction (NSTEMI) and ST-segment elevation myocardial infarction (STEMI)[1]. The main mechanism of ACS is vulnerable plaque rupture or ulcer combined with thrombosis and (or) vascular spasm, causing a sharp increase in the degree of coronary stenosis or acute occlusion[2]. Culprit lesion of ACS is often due to the stenosis caused by vulnerable plaque, but the stenosis may not be severe[3]; for patients with ACS, in addition to culprit plaques, multiple vulnerable plaques often coexist in the different segments of the same coronary artery or in different coronary arteries[4], which may increase the risk of death during the acute phase and recurrent ischemic events[5]. The particularity of coronary artery diseases and plaques of ACS patients determines the importance of statin therapy (referred to as 'statin'). 2011 European Society of Cardiology / European Atherosclerosis Society (ESC / EAS) Guidelines for Management of Dyslipidaemias continue to affirm the cornerstone status of statins in the treatment of ACS patients; for such patients at very high risks, early initiation of statin therapy should be actively recommended[6]. 2. Current application of statins for Chinese ACS patients: The proportion of Chinese ACS patients receiving statin therapy, especially the intensive statin therapy, is generally low. In the study of Clinical Pathway for Acute Coronary Syndromes in China (CPACS), only 80% of ACS patients are taking statins when discharged; one year later, only about 60% of patients are still taking statins[7]. Even for the patients taking statins, a considerable proportion of them fail to reach the target dose recommended by the guidelines. There is a huge gap between the guidelines or evidence of evidence-based medicine and clinical practice. As a result, formulating relevant guidelines and consensus is of great significance for popularizing statin therapy (especially the intensive statin therapy) for ACS patients and improving the prognosis of ACS patients. II. Recommendations on Intensive Statin Therapy1. Main intended population: All ACS patients, including those undergoing emergent percutaneous coronary intervention (PCI), elective PCI or medical therapy. 2. Definition of intensive statin therapy: Intensive statin therapy refers to the high-dose statin therapy and (or) the statin therapy in which low density lipoprotein cholesterol (LDL-C) value is significantly reduced. In acute intensive statin therapy, the dose of statin is enhanced, and the maximum tolerated dose recommended by the instruction book of the statin product should be adopted to protect myocardium and reduce the incidence of perioperative myocardial infarction and major adverse cardiac events[1,8-22]; long-term intensive statin therapy aims at achieving the therapeutic goal; it is recommended to reduce LDL-C level to below 70 mg/dl(1.8 mmol/L) or reduce it by more than 50%; the purpose of long-term intensive statin therapy is to reduce short and long term cardiovascular events and death and ultimately improve the prognosis of ACS patients[1, 20-14]. 3. Specific treatment regimens (1) After ACS patients are admitted to the hospital, intensive statin therapy should be initiated as soon as possible (within 24 hours)[1,8-22]. (2) After admission, routine baseline serum lipid level detection should be performed within 24 hours, but intensive statin therapy does not depend on the baseline serum lipid levels; the patients with the baseline LDL-C levels below 70 mg/dl can also benefit from intensive statin therapy[9]. (3) High doses of statins are generally used, such as atorvastatin 80 mg (once daily)[8-9,11-12,15-18,20-22]. (4) The target of long-term intensive statin therapy is LDL-C <70 mg/dl or decrease by > 50%[8-9]. (5) Booster dose statin therapy should be maintained for3 ~ 6 months during which the serum lipid levels should be reexamined and the dose of statin should be appropriately adjusted to ensure that the LDL-C level is below 70 mg/dl or decreases by>50%[8-12,14, 23-24]. 4. Procedures of intensive statin therapy for ACS patients are shown in Figure 1. III. Safety of Intensive Statin TherapyThe low proportion of ACS patients receiving intensive statin therapy is mainly due to safety concerns; existing evidence-based evidence shows that the overall safety of intensive statin therapy for ACS patients is good[26] with benefits far outweighing the risks. However, for different individuals, side effects for liver, kidney, muscle and other organs should be considered before initiation of intensive statin therapy; therefore, clinical benefits and risks of adverse reactions should be weighed before initiation of intensive statin therapy and relevant indicators should be monitored during intensive statin therapy for the elderly patients with liver and kidney dysfunction, history of adverse reactions to statins, low body weight, hypothyroidism or potential drug interactions. 1. Hepatic safety: All statin therapy can cause elevated liver enzymes with the incidence of less than 1%; elevated liver enzymes alone are not indicative of hepatic injury. Patients with statin therapy-related hepatic failure are rare, so routine periodic detection of liver enzymes is not recommended[27-28]. Increase in transaminase to<3×ULN should not be considered as a contraindication for statin therapy. If transaminase is increased to>3×ULN, statin therapy should be discontinued; after liver enzymes return to normal, a continuation to use of statin therapy can be considered, or the statin therapy can be replaced with another therapy[29-30]. Non-alcoholic fatty liver disease, chronic liver disease and compensatory cirrhosis are not contraindications for statin therapy[27,31]. However, the relationship between benefits and risks should be carefully evaluated for patients with existing severe acute liver injury or active hepatitis. 2. Muscle safety: Different statins have different incidences of severe muscle adverse events, but the overall incidence is low[29]. Mild asymptomatic elevated creatine kinase (CK) is common[30], so routine monitoring of CK levels is not recommended after initiation of statin therapy unless muscle symptoms occur to in the patients, such as muscle pain, muscle weakness, etc[29]. Once muscle symptoms occur and CK level exceeds 5×ULN, statin therapy should be stopped[30]. A retrospective analysis shows that high doses of simvastatin may increase the risk of muscle damage and should be used with caution for clinical use[32]. 3. Renal safety: Renal safety of statins is heterogeneous[33]. For patients with good renal function, it is safe to use statins. For patients with the estimated glomerular filtration rate (eGFR) of<30 ml/(min·1.73 m2), the doses of statins other than atorvastatin and fluvastatin should be adjusted[34] and rosuvastatin should be forbidden[35]. 4. Other safety: (1) New-onset diabetes: Statin therapy may slightly increase the risks of new-onset diabetes[12,36-37], but the cardiovascular benefits of statin therapy far outweigh the risks of new-onset diabetes[37], therefore, there is no need to change the existing treatment recommendations. However, for patients with impaired fasting glucose or metabolic syndrome, it is recommended to monitor blood glucose levels during statin therapy. (2) New-onset tumors: The relationship between statin therapy and new-onset tumors is unclear. Generally speaking, statin therapy does not increase the risk of tumors[38]. (3) Safety for the Asian population: Relevant research is limited, but the latest retrospective analysis shows that the safety of atorvastatin 10~80 mg (once daily) for Asian patients is good and equivalent to that for European and American patients[39]. 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Am J KidIley Dis, 2012,60：850-886． [35] 瑞舒伐他汀钙片说明书．核准日期：2006年12月27日，修改日期：2011年1月5日． [36] Ridker PM，Damielson E, Fonseca FA，et al．Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein．N Engl J Med，2008，359：2195-2207． [37] sattar N，Preiss D，Murray HM，et al. Statins and risk of incident diabetes：a collaborative meta-analysis of randomised statin trials．Lancet, 2010, 375:735-742． [38] Mihaylova B，Emberson J，Blackwell L，et al．The efTects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease：meta-analysis of indiVidual data from 27 Randomized trials．Lancet，2012，380：58l-590． [39] Chan J，Bao WH，Fayyad R，et al. Analysis of safety of Atorvastatin in Asian Patient C1inical Trial. Heart,2012,98(suppl 2)：E316． END 转载须经原作者授权。  《门诊》杂志官方微信 |
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