Factors Associated with Lipid Goal Attainment among Patients with Deployed Drug Eluting Stent

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1 Original Article Acta Cardiol Sin 2014;30: Lipids Factors Associated with Lipid Goal Attainment among Patients with Deployed Drug Eluting Stent Min-I Su, 1 Cheng-Ting Tsai, 1 Hung-I Yeh 1,2 and Chun-Yen Chen 1,2 Background: Drug-eluting stents (DES) have provided significant benefits for patients with complex coronary lesions. Intensive lipid control through statin therapy decreases the risk of late target lesion revascularization in patients with implanted DES. Therefore, we investigated lipid management in patients with implanted DES and analyzed the predictors for achieving target lipid goals. Methods: A retrospective study was performed on consecutive patients who underwent percutaneous coronary intervention (PCI) with DES deployment from 2010 to Fasting lipid profiles were obtained for all patients both on the day of and 6 months after PCI. Logistic regression analysis was used to predict factors for achieving target lipid goals. Results: A total of 419 patients (mean age: 62; 80% men) were included. Only 20.8% of patients achieved the target low-density lipoprotein cholesterol (LDL-C) level of < 70 mg/dl, and 61.6% of patients achieved the target LDL-C level of < 100 mg/dl. An equivalent dose of statins was statistically significant in attaining LDL-C levels of < 70 mg/dl [adjusted odds radio (AOR): 1.30; p < 0.001] and < 100 mg/dl (AOR: 1.27; p < 0.001). In addition, a baseline LDL-C level < 130 mg/dl is a leading predictor of achieving target LDL-C levels (AOR: 2.3, p = for LDL-C < 70 mg/dl; AOR: 2.01, p = for LDL-C < 100 mg/dl). Conclusions: Achievement of target LDL-C levels is difficult in patients with implanted DESandabaselineLDL-C level of 130 mg/dl who are not treated with statins. Therefore, these patients should be treated with more aggressive statin therapy. Key Words: Drug-eluting stents Low density lipoprotein INTRODUCTION Dyslipidemia is a major risk factor for cardiovascular disease. 1 Research over the last 2 decades has demonstrated that statin treatment reduces the risk of developing cardiovascular events. 2-5 Reducing low-density Received: July 16, 2013 Accepted: January 20, Division of Cardiology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei; 2 Mackay Medical College, New Taipei City, Taiwan. Address correspondence and reprint requests to: Dr. Chun-Yen Chen, Cardiovascular Division, Department of Internal Medicine, Mackay Memorial Hospital, No. 92, Sec. 2, Chung Shan North Road, Taipei 10449, Taiwan. Tel: ext. 2456; Fax: ; mwplasma@ms9.hinet.net Min-I Su and Cheng-Ting Tsai contributed equally to this article. lipoprotein cholesterol (LDL-C) levels has been the critical goal in lipid modification for the treatment and prevention of coronary artery disease (CAD). The National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III recommends administration of treatment to achieve a target LDL-C level of < 100 mg/dl in patients with established CAD, with an optional therapeutic target level of < 70 mg/dl in very high-risk patients. 6 The European Society of Cardiology and the European Atherosclerosis Society guidelines for the management of dyslipidemia suggest that the target LDL-C level should be < 70 mg/dl for patients with established CAD. 7 The Taiwanese Secondary Prevention for patients with Atherosclerotic Disease (T-SPARCLE) Registry reveals that only 54% of patients with atherosclerotic disease (patients with established CAD, cerebrovascular 325 Acta Cardiol Sin 2014;30:

2 Min-I Su et al. disease, or peripheral arterial disease) achieved the ATP III targets for LDL-C. The obvious variation in the proportion of patients achieving target lipid levels among clinical practices was reported in a previous study. 8,9 Drug-eluting stents (DES) are commonly used in clinical practice and provide significant benefits for patients with diabetes, multi-vessel disease, left main coronary artery disease, smaller coronary arteries, or long lesions. 10 Although DES can better decrease the rate of repeat revascularization compared with bare metal stents, previous optical coherence tomography studies indicated that atherosclerotic changes such as lipid-rich neointima and thin-cap fibroatheroma-like neointima, significantly increased in patients with late in-stent restenosis (ISR) after DES implantation. 11,12 Moreover, statin therapy decreases late target lesion revascularization (TLR) in patients treated with DES, 13 and high-intensity statin therapy leads to a significant regression of atherosclerosis. 14 Accordingly, patients treated with DES had greater disease complexity and need to undergo more aggressive treatment such as a prolonged regimen of dual anti-platelet therapy and intensive lipid-lowering therapy, to achieve target LDL-C levels. However, there is a paucity of real-life data addressing the achievement of target LDL-C levels in patients treated with DES. Therefore, we conducted this retrospective study to estimate the proportion of patients treated with DES who achieved target LDL-C levels (< 100 mg/dl or < 70 mg/dl) at 6 months after percutaneous coronary intervention (PCI). Additionally, we used SYNTAX score to quantify the anatomical severity of CAD 15,16 and investigated the proportion of LDL goal attainment between different severities of CAD. MATERIALS AND METHODS Subjects This study was conducted in accordance with the Declaration of Helsinki and approved by the Institutional Review Board of Mackay Memorial Hospital (13MMHIS 098). Of 4314 consecutive patients referred for coronary catheterization from 2010 to 2012, 1930 patients underwent PCI. We identified 419 consecutive patients who underwent PCI with the deployment of DES from Mackay Memorial Hospital from 2010 to 2012 and who had completed a lipid follow-up 6 months thereafter. The indications for referral included ischemia that was documented by either resting electrocardiogram or stress testing, or typical stable angina of Canadian Cardiovascular Society class II or III. Demographic data, disease history, tobacco use, coronary angiographic results, and prescribed medications were obtained from the hospital medical registry. The blood lipid profile [TC (total cholesterol), high-density lipoprotein cholesterol (HDL-C), LDL-C,andtriglycerides(TG)],andglycatedhemoglobin (HbA1C) and creatinine (Cr) levels were evaluated both on the day of PCI and 6 months after PCI. All blood samples were collected by venipuncture at least 8 hours after fasting. Hypertension (HTN) was defined as present in patients with a history of HTN or a systolic blood pressure (BP) of 140 mmhg or a diastolic BP of 90 mmhg. Patients were defined as having diabetes mellitus (DM) if they had a history of DM, HbA1C levels of 6.5%, or if they were taking oral hypoglycemic agents or using insulin. Based on the Modification of Diet in Renal Disease study, the estimated glomerular filtration rate (egfr) was calculated using the following formula: egfr (ml min m -2 ) = 186 (serum Cr) (age) (0.742) (if female). Patients were defined as having uremia if they were undergoing maintenance hemodialysis. Coronary angiography was performed using a Philips Integris BH 5000 equipped with the cardiovascular angiography analysis system, CAAS II (Best, Netherlands). All angiographic variables pertinent to SYNTAX score calculation were computed by 2 experienced cardiologists (C.T.T and C.Y.C.). A major adverse cardiovascular event (MACE) was defined as sudden cardiac death, acute coronary syndrome, TLR and stroke. All patients treated with DES were regularly followed-up in interventional cardiologists clinics, and such followup was continued until May 30, Statistical analysis Results are expressed as the mean standard deviation (SD) or as percentages. The Student s t test was used to compare differences between groups for continuous variables, and the chi-squared test was employed for categorical data. The blood lipid profile measured on the day of PCI was defined as the baseline lipid profile. The primary study outcome measure was the rate of attainment of target lipid level, which was the Acta Cardiol Sin 2014;30:

3 Lipid Control and Drug Eluting Stents proportion of patients who achieved their target LDL-C levels of < 100 mg/dl or the optional < 70 mg/dl at 6 months after PCI. Logistic regression was used to calculate the odds ratios of achieving target lipid goal to determine which variables contributed to success or failure in target achievement after PCI; failure to achieve the target lipid level was used as the reference. The odds ratios (95% confidence intervals) were adjusted for baseline lipid levels, sex, age, HTN, DM, tobacco use, and statin use or a statin-equivalent dose. The equivalent statin doses were calculated similar to those calculations in the T-SPARCLE study. 8 Ap-valueof<0.05was considered statistically significant. All statistical analyses wereperformedwithspsssoftware,version19(ibm SPSS Statistics, Binghamton, NY, USA). RESULTS A total of 419 patients treated with DES were included in the analysis and follow-up period (median: 804 days). Of these patients, 77.3% received statin treatment, and 1 patient had an allergy to statin. Medical records indicated that none of the patients was intolerant of lipid-lowering agents. We divided patients into 2 groups according to 2 different target LDL-C levels (< 100 mg/dl or < 70 mg/dl). A total of 258 (61.6%) patients achieved an LDL-C level of < 100 mg/dl, and 87 (20.8%) patients further achieved the optional target LDL-C level of < 70 mg/dl at 6 months after PCI. Age, sex, tobacco use, HTN, DM, percentage of ACS, egfr, and baseline TG and HDL-C levels did not differ between patients with an LDL-C level of < 100 mg/dl and those with an LDL-C level of 100 mg/dl. A total of 23 patients (5.5%) combined were treated with statin and other lipid-lowing agents. The proportion of patients taking statins combined with other lipid-lowering agents (such as fibrates or ezetimibe) was not different in patients of target LDL-C levels (< 100 mg/dl or < 70 mg/dl). The HDL-C and TG levels at 6 months after baseline also did not differ between patients with an LDL-C level of < 100 mg/dl and those with an LDL-C level of 100 mg/dl. However, the baseline and 6-month followup levels of TC and LDL-C were significantly lower in patients who achieved the target LDL-C level of < 100 mg/dl than in those who did not. The proportion of patients taking statins was also significantly higher in the group of patients who achieved the target LDL-C level of < 100 mg/dl. The SYNTAX scores did not differ between patients who achieved and those who did not achieve the LDL-C goal level of < 100 mg/dl. Similar results to thosementionedabovewerealsoobservedinthecomparison of patients with an LDL-C level of < 70 mg/dl and those with an LDL-C level of 70 mg/dl, except for baseline TC (Table 1). Besides, the rate of MACE did not differ in patients of target LDL-C levels (< 100 mg/dl or <70mg/dL). Baseline LDL-C levels were divided into groups that were 130 mg/dl and those that were < 130 mg/dl. A total of 107 patients had baseline LDL-C more than 130 mg/dl but only 10 of them (9.3%) did not receive lipidlowering treatment. We further divided patients into 4 groups according to baseline LDL-C levels ( 130 mg/dl, <130mg/dL)andstatinuse(yes,no).Comparedwith other groups, patients with a baseline LDL-C level of < 130 mg/dl and who receive statin therapy have an increased probability of achieving the target LDL-C level (Figures 1A, B). To further clarify the factors associated with effective control of dyslipidemia, a logistic regression model was employed (Table 2). The independent variables of the regression model included age, sex, tobacco use, HTN, DM, baseline LDL-C level (< 130 mg/dl vs. 130 mg/dl), and statin use or equivalent doses of statins. Patients with a baseline LDL-C level of < 130 mg/dl were more likely to achieve an LDL-C level of < 70 mg/dl (AOR: 2.30; p = 0.01) or < 100 mg/dl (AOR: 2.01; p = 0.006) than those with a baseline LDL-C level of 130 mg/dl. Statin use was statistically significant in achieving an LDL-C level of < 70 mg/dl (AOR: 7.71; p < 0.001) or < 100 mg/dl (AOR: 4.63; p < 0.001). An equivalent dose of statins also increases the probability of achieving an LDL-C level of < 70 mg/dl (AOR: 1.30; p < 0.001) or < 100 mg/dl (AOR: 1.27; p < 0.001). Patients with a baselineldl-clevelof<130mg/dlweremorelikelyto achieve an LDL-C level of < 70 mg/dl (AOR: 2.30; p = 0.012) or < 100 mg/dl (AOR: 2.01; p = 0.006) than those with a baseline LDL-C level of 130 mg/dl. We calculated the SYNTAX score for 399 patients who did not undergo coronary artery bypass grafting (CABG). The 20 patients with a history of CABG were excluded because the SYNTAX score cannot be calculated 327 Acta Cardiol Sin 2014;30:

4 Min-I Su et al. Table1. Patients and clinical characteristics grouped according to lipid goal attainment (100 md/dl and 70 mg/dl) LDL-C < 70 (N = 87) LDL-C 70 (N = 332) pvalue LDL-C < 100 (N = 258) LDL-C 100 (N = 161) pvalue Age (year)s Male (%) 68 (78%) 267 (80%) (81%) 125 (78%) 0.35 Smoking status (%) 26 (30%) 117 (35%) (31%) 064 (40%) 0.06 Current diseases HTN (yes, %) 59 (68%) 241 (73%) (73%) 112 (70%) 0.47 DM (yes, %) 42 (48%) 137 (41%) (45%) 064 (40%) 0.33 egfr (ml/min) (83)* (328) (251) (160) 0.48 Hemodialysis 4 (4.6%) 00.4 (1.2%) (2.7%) 0.1 (0.6%) 0.16 ACS (yes, %) 25 (29%) 078 (25%) (24%) 44 (29%) 0.40 Blood lipids before PCI TC (mg/dl) TG (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) Blood lipids 6 months after PCI TC (mg/dl) TG (mg/dl) LDL-C (mg/dl) HDL-C (mg/dl) Medication Statin use (yes, %) 82 (94%) 242 (72%) (86%) 102 (63%) Other lipid-lowering agents (yes,%) 6 (1.1%) 17 (5.1%) (3.9%) 0.13 (8.1%) 0.66 Statin equivalent dose Syntax score MACE Total 7 (8%) 20 (6%) (7.4%) 8 (5%) 0.42 ACS 3 (3.4%) 6 (1.8%) (2.7%) 0.2 (1.2%) 0.49 SCD 0 (0%) 00.2 (0.6%) (0.8%) 0 (0%) 0.53 TLR 4 (4.6%) 00.9 (2.7%) (3.5%) 0.4 (2.5%) 0.77 stroke 0 (0%) 3 (0.9%) (0.4%) 0.2 (1.2%) 0.56 ACS, acute coronary syndrome; DM, diabetes mellitus; egfr, estimated glomerular filtration rate; HDL, high density lipoprotein; HTN, hypertension; LDL, low density lipoprotein; MACE, major adverse cardiovascular event; PCI, percutaneous coronary intervention; SCD, sudden cardiac death; TC, total cholesterol; TG, total triglycerides; TLR, target lesion revascularization. (N): number of non-hemodialysis patients. Other lipid-lowering agents: included fibrates and ezetimibe. for these patients. The patients were divided into 3 groups on the basis of their SYNTAX score (< 23, or > 33). There was no statistical difference in achieving an LDL-C level of < 70 mg/dl (21%, 22%, and 27% for patients in the group with a SYNTAX score of < 23, or > 33, respectively; p = 0.77) or < 100 mg/dl (64%, 54%, and 63% for the same groups, respectively; p = 0.27) (Figures 2A, B). Additionally, only 5% of patients with CABG could achieve the optional target LDL-C level of < 70 mg/dl, while 50% of patients with CABG achieved thetargetldl-clevelof<100mg/dl. DISCUSSION Our study demonstrated that only a small proportion (20.8%) of patients achieved the optional target LDL-C level of < 70 mg/dl, and 61.6% of patients achievedthetargetldl-clevelof<100mg/dl.inparticular, patients who do not take statins with a baseline LDL-C Acta Cardiol Sin 2014;30:

5 Lipid Control and Drug Eluting Stents Table 2. Factors related to LDL goal attainment Variable Goal: LDL < 70 Goal: LDL < 100 AOR (95% CI) p value AOR (95% CI) p value Model 1 Gender (male vs. female) 0.88 ( ) ( ) 0.06 Age (per year) 0.99 ( ) ( ) 0.31 Smoking (yes vs. no) 0.73 ( ) ( ) 0.08 HTN (yes vs. no) 0.66 ( ) ( ) 0.94 DM (yes vs. no) 1.57 ( ) ( ) 0.18 Statin use (yes vs. no) 7.71 ( ) < ( ) < Baseline LDL (< 130 vs. 130) 2.37 ( ) ( ) Model 2 Gender (male vs. female) 0.86 ( ) ( ) 0.09 Age (per year) 1.00 ( ) ( ) 0.18 Smoking (yes vs. no) 0.67 ( ) ( ) 0.04 HTN (yes vs. no) 0.78 ( ) ( ) 0.53 DM (yes vs. no) 1.47 ( ) ( ) 0.42 Statin equivalent dose (per dose) 1.30 ( ) ( ) Baseline LDL (< 130 vs. 130) 2.30 ( ) ( ) Abbreviations as in Table 1. AOR, adjusted odds ratio; DM, diabetes mellitus; HTN, Hypertension; LDL, low-density lipoprotein. A A B Figure 1. (A) Proportion of patients attaining their low-density lipoprotein cholesterol (LDL-C) goals of < 70 mg/dl according the baseline LDL and statin use. (B) Proportion of patients attaining their low-density lipoprotein cholesterol (LDL-C) goals of < 100 mg/dl according the baseline LDL and statin use. B Figure 2. (A) Proportion of patients attaining their low-density lipoprotein cholesterol (LDL-C) goals of < 70 mg/dl according the SYNTAX score. (B) Proportion of patients attaining their low-density lipoprotein cholesterol (LDL-C) goals of < 100 mg/dl according the SYNTAX score. 329 Acta Cardiol Sin 2014;30:

6 Min-I Su et al. level of 130 mg/dl are less likely to achieve the target LDL-C levels. The Lipid Treatment Assessment Project reported that 30.1% of 9955 evaluated patients achieved the optional target LDL-C level of < 70 mg/dl, and 72.7% of patients achieved the target LDL-C level of < 100 mg/dl. 17 In The NCEP Evaluation ProjecT Utilizing Novel E-Technology (NEPTUNE) II study, 62% of 1322 patients with coronary heart disease achieved an LDL-C level of < 100 mg/dl, and 17.8% of those at very high risk achieved an LDL-C level of < 70 mg/dl. 18 In the Clinical Pharmacy Cardiac Risk Service, a substantial proportion (43%) of very-high risk patients with CAD achieved the target LDL-C level of < 70 mg/dl with current lipidlowering therapy; the majority (88.1%) of those patients achieved the target LDL-C level of < 100 mg/dl. 19 The findings of our present study are consistent with those of the abovementioned studies. The CEPHEUS Indonesian Survey reported that 12.1% of patients achieved the target LDL-C level of < 70 mg/dl, and 34.2% of patients achieved the target LDL-C level of < 100 mg/dl. 20 Our study revealed a gap between clinical practice and the guidelines among patients with DES deployment. DES are commonly employed and have demonstrated significant benefit for patients with diabetes or complex CAD such as multi-vessel disease, left main disease, smaller coronary arteries, or long lesions. 10 Statin therapy reduced restenosis rates after coronary stent implantation In addition, statin therapy was associated with a significantly decreased risk for TLR after DES implantation. 13 Patients treated with high-intensity statin therapy and who achieved an LDL-C level of < 70 mg/dl experienced significant regression of atherosclerosis. 14 These studies demonstrate that statin treatment has an important role in reducing ISR. The present study indicates that a baseline LDL-C level of < 130 mg/dl is the leading predictor for achieving the target LDL-C level at 6 months after PCI. Likewise, previous studies have shown that baseline LDL-C level is inversely associated with the achievement of target LDL-C levels. 23 In our study, 9.3% of patients with LDL-C levels of 130 mg/dl did not receive the lipid lowering agents. Moreover, Chin et al. indicated that failing to up-titrate doses was present in more than 2/3 of patients with ACS in one year follow-up. 24 The causes why patients with LDL 130 mg/dl did not reach their lipid goal 6 months thereafter may be due to poor guideline adherence. Therefore, our study suggests that physicians should devote more attention to patients with baseline LDL-C levels of 130 mg/dl. Moreover, an equivalent dose of statins is another significant contributor in lipid control to achieve a target LDL-C level of < 70 mg/dl or < 100 mg/dl. The previous study revealed that treatment with higher doses of statins could increase the probability of target LDL-C level. 25 In our study, statin use and increased statin dose led to a higher probability of achieving the target lipid level. Consequently, therapeutic strategies for patientstreatedwithdesandabaselineldl-clevelof 130 mg/dl should be more aggressive with higher dosages of statins than those prescribed for other patients. Our study demonstrated that the achievement of target LDL-C level was not affected by SYNTAX scores. This highlights a critical issue: that physicians commonly lack awareness that patients with complex CAD should be treated with aggressive lipid-lowering therapy. Additionally, patients with high SYNTAX scores should be treated with higher doses of statins to achieve an LDL-C level of < 70 mg/dl and decrease their risk for TLR. Failure to achieve target LDL-C levels can be the result of many factors such as a lack of follow-up, improper titration of the starting statin dose, poor adherence to treatment, insurance payment, and safety issues with statin therapy. A physician may choose not to prescribe intensive statin treatment because of concern about statin safety issues, lack of awareness, attitude, lack of knowledge of the guidelines or local barriers to implementation of the guidelines. In addition, the National Health Insurance (NHI) primarily covers medical expenses in Taiwan, and insurance payment policies directly influence physician decision-making. Unfortunately, the current therapeutic target LDL-C level in Taiwan for very high-risk patients is < 100 mg/dl, and NHI payment policy strongly restricts the willingness of physicians to prescribe statins or titrate statins aggressively to a higher dose. The present data illustrate that the gap between achieving target LDL-C levels and statin therapy is still widening in clinical practice. Accordingly, guideline adherence should be promoted. In addition to revising the National Health Insurance reimbursement guideline, we should devote more substantial effort to developing an audit system to monitor guideline adherence for lipid management in high-risk CAD patients, and other methods such as self-audit of Acta Cardiol Sin 2014;30:

7 Lipid Control and Drug Eluting Stents practice, focused continuing medical education programs, educational outreach programs and a call for improved public awareness. However, our data did not include the behavior of lipid management between physicians. The primary limitation of our study is that it was a retrospective observational study at a single center, and therefore not a nationally representative sample or a randomized prospective study. Consequently, our findings may not be applicable to other CAD patients at other hospitals or in the general population. The true incidence of achievement of target lipid levels could be estimated from our study. However, this study provides benchmark data for the quality of lipid management with respect to the rate of target level achievement for patients treated with DES. Our study also considered the changes in lipid values over time, and was different from other cross-sectional studies in which only 1 lipid value was analyzed. The etiology influencing the target achievement by lipid-lowering treatment may be multifaceted. However, other factors beyond the scope of our study may influence achievement of target LDL-C levels such as genetic factors, physical activity, psychological factors, socioeconomic status, adherence to medication, and physician awareness of the guideline. In our study, the number of patients using other lipid lowering agents is too small to reach any conclusions regarding the effect of the combined statin and other lipid lowering agents, or only other lipid lowing agents on achieving target lipid goal. A satisfactory explanation as to why there was no difference in MACE may be the small number of patients and shorter follow-up period. In addition, our study only investigated the LDL-C level at 6 months after PCI, but side effects of the drugs, and other outcomes were not explored. Thus, further prospective interventional research should be performed to confirm the present data. CONCLUSIONS Our study demonstrated that a lower proportion of patients achieved the lower target LDL-C level of < 70 mg/dl. Improvement in lipid management is needed in real-world clinical practice relative to the guidelines for patients treated with DES. A baseline LDL-C level of < 130 mg/dl and statin treatment are the primary predictors for the achievement of target LDL-C levels. To achieve these goals, patients with a baseline LDL-C level of 130 mg/dl should be treated with more aggressive statin therapy than other patients. CONFLICTS OF INTEREST None. REFERENCES 1. Stamler J, Wentworth D, Neaton JD. Is relationship between serum cholesterol and risk of premature death from coronary heart disease continuous and graded? Findings in 356,222 primary screenees of the Multiple Risk Factor Intervention Trial (MRFIT). JAMA 1986;256: Lardizabal JA, Deedwania P. Lipid-lowering therapy with statins for the primary and secondary prevention of cardiovascular disease. Cardiol Clin 2011;29: Baigent C, Keech A, Kearney PM, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomized trials of statins. Lancet 2005;366: Mills EJ, Rachlis B, Wu P, et al. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. JAmColl Cardiol 2008;52: Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170,000 participants in 26 randomised trials. Lancet 2010;376: Fihn SD, Gardin JM, Abrams J, et al ACCF/AHA/ACP/AATS/ PCNA/SCAI/STS Guideline for the diagnosis and management of patients with stable ischemic heart disease. A Report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American College of Physicians, American Association for Thoracic Surgery, Preventive Cardiovascular Nurses Association, Society for Cardiovascular Angiography and Interventions, and Society of Thoracic Surgeons. J Am Coll Cardiol 2012;60.24:e Reiner, Catapano AL, De Backer G, et al. ESC/EAS Guidelines for the management of dyslipidaemias. The Task Force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J 2011;32: Chen CY, Chuang SY, Fang CC, et al. Gender difference in statin intervention on blood lipid control among patients with coronary heart disease. Int J Gerontol 2013;7: Acta Cardiol Sin 2014;30:

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