新指南安全性解读

2013 ACC/AHA 降低成人动脉粥样硬化性心血管风险胆固醇治疗指南,朱源生 淮安第二人民医院,2013 AHA/ACC 新指南推荐大部分4类他汀获益人群使用高强度他汀,Stone NJ, et al. JACC (2013), doi: 10.1016/j.jacc.2013.11.002.,已存在ASCVD 如无禁忌症或年龄10ULN，且不伴肌肉症状,对44项阿托伐他汀高质量研究，共 16,495名患者的回顾性分析证实，阿托伐他汀肌肉安全性良好,Newman CB, et al. Am J Cardiol 2003;92:670676,阿托伐他汀80mg肌肉安全性与10mg相当,入选49项阿托伐他汀研究，共14,236名患者的安全性数据。比较阿托伐他汀10mg和80mg在治疗相关不良反应、肌肉、肝脏、肾脏方面的安全性,Am J Cardiol 2006;97:6167,肌痛发生率（%）,(n=7258),(n=4798),临床中，如何选择安全他汀？,出血性卒中亚裔人群安全性肌肉安全性肾脏安全性,Shepherd J et al. J Am Coll Cardiol. 2008;51:1448-1454. 霍勇,何华. 北京大学学报;2007,39(6):624-629,ASCVD患者常合并CKD,合并CKD(N=3,107),不合并CKD(N=6,894),回顾性分析，入选3,589名接受过介入治疗的ACS患者，根据患者入院时行造影前血清肌酐水平，运用简化 MDRD方程对所有患者估算肾小球滤过率（eGRF）,FDA强调瑞舒伐他定的安全剂量是20mg/d,March 3, 2005 - The FDA has issued a public health advisory to further explain the risks and benefits of the cholesterol-lowering drug Crestor. The drug will now carry a new label that includes new recommended doses for patients at a higher risk of muscle damage, including Asian patients. People taking the immune suppressing drug cyclosporine, such as organ transplant patients ;Patients with severe kidney failure,2003.7.92004.3.4;美、英、加报告：服用瑞舒伐他汀大多在小剂量短时间发生肌溶与肾衰,7 patients with rhabdomyolysis (patients using doses of 10, 20, 20, 20-40, 40, 40 and 80 milligrams per day)4 patients with acute kidney failure (patients using 10, 10, 10 and 40 milligrams per day)5 additional patients with kidney damage (patients using 10, 10, 10, 20 and 40 milligrams per day)6 patients with bleeding or abnormal bleeding tests who were also using blood-thinning drugs such as coumadin, known to have an abnormal interaction with rosuvastatin (patients using 10, 10, 10, 10, 20 and unknown milligrams per day),Petition to Ban Cholesterol-Lowering Drug Rosuvastatin (Crestor) Public Citizen March 4, 2004,PLANET研究：头对头比较两个强他汀的肾脏影响,PLANET I and II: Atorvastatin beats rosuvastatin for protecting kidneys in diabetic and nondiabetic patients,对蛋白尿的影响： 阿托伐他汀显著减少蛋白尿,对肾功能的影响（eGFR）： 阿托伐他汀优于瑞舒伐他汀,Heartwire JULY 5, 2010 Daniel M Keller,Atorvastatin 80mg/day significantly reduced proteinuria by about 20%. Rosuvastatin 10 or 40mg/day had no effect on proteinuria. Rosuvastatin 40mg/day was associated with a significant decline in eGFR of about 8mL/min per 1.73m2 per year. Atorvastatin 80mg/day had no effect on eGFR. Atorvastatin 80mg/day has a clear advantage over rosuvastatin 40mg/day in terms of renal protection and renal damage.,PLANET : Atorvastatin beats rosuvastatin for protecting kidneys in diabetic and nondiabetic patients,临床研究一致显示，阿托伐他汀对肾脏无不良影响,eGFR改变,CrCl改变,eGFR改变,eGFR改变,eGFR改变,0.18ml/min/1.732/年P = 0.01,12%P 0.0001,5.2ml/min/1.732P 0.0001,0.8ml/min/1.732P = 0.008,5.21ml/min/1.732P = 0.026,Colhoun HM, et al. Am J Kidney Dis. 2009;54:810-819Athyros VG, et al. J Clin Pathol. 2004;57:728734Shepherd J, et al. Clin J Am Nephrol. 2007;2:1131-1139Koren MJ, et al. Am J Kidney Dis.2009; 53:741-750Holme I, et al. J Intern Med. 2010;267: 567575,CKD-慢性肾脏疾病；eGFR-估算肾小球滤过率；CrCl-肌酐清除率,CARDS 1糖尿病+CKD立普妥10mg vs 安慰剂,GREACE 2冠心病+CKD立普妥24mg vs 常规治疗,TNT 3冠心病+CKD立普妥80mg vs 10mg,ALLIANCE 4冠心病+CKD立普妥40mg vs 常规治疗,IDEAL 5冠心病+CKD立普妥80mg vs辛伐他汀20-40mg,阿托伐他汀用于CKD合并血脂异常患者无需调整剂量,2011 欧洲血脂异常管理指南对CKD患者的他汀治疗说明 4,中等剂量的他汀在CKD1-2期患者具有良好的总体耐受性。但在较严重的CKD患者（3-5期），由于他汀治疗的不良事件常常与剂量和血药浓度增加相关，因此他汀治疗的安全问题和剂量调整尤显重要，此时应选择最少经肾脏排泄的他汀（阿托伐他汀）,立普妥产品说明书. 2013年4月12日版舒降之产品说明书. 2010年7月5日版可定产品说明书. 2011年1月5日版European Heart Journal. 2011;32:17691818,总结,2013 AHA/ACC新指南推荐大部分4类他汀获益人群使用高强度他汀，并明确了2类高强度他汀：阿托伐他汀40-80mg；瑞舒伐他汀20-40mg临床如何选择更安全的高强度他汀？对于出血性卒中：他汀类药物用于卒中一级预防人群中不增加脑出血的风险；针对卒中二级预防人群中有脑出血病史及脑出血高风险人群应权衡风险和获益合理使用用于亚裔人群：瑞