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中国胆固醇教育计划培训教材

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血脂管理的中国专家共识和中国观点荟萃
Content Description

《中国胆固醇教育计划培训教材》是血脂管理的中国专家共识和中国观点荟萃,策划编写过程中特别强调了针对性和临床实用性。针对国际、国内近期在这一领域出现的争议和混乱,并基于全新的研究结果,更加旗帜鲜明地坚守百年胆固醇学说,与时俱进地推动胆固醇定律的落实,客观全面地介绍和评价他汀的安全性,消除对他汀降胆固醇以外的多效性的误解,努力消除荒谬的“序贯疗法”对我国临床的误导,推动中国动脉粥样硬化性心血管病防控的规范化和现代化。
Author Description

胡大一,主任医师,教授,博士生导师,著名心血管病专家,医学教育家,国家和首都突出贡献专家,享受国务院政府专家津贴。中国康复医学会心血管病专业委员会主任委员,中华预防医学会副会长,中国控制吸烟协会会长,中国心脏联盟主席。
Catalogue

血脂异常防治的中国专家共识
§ 2014年中国胆固醇教育计划血脂异常防治专家建议
§ 选择性胆固醇吸收抑制剂临床应用专家共识(2015)
§ 他汀类药物安全性评价专家共识
§ 血脂异常老年人使用他汀类药物中国专家共识
国外指南与指南评析
§ 2013年美国心脏病学学会和美国心脏协会降低成人动脉粥样硬化心血管风险胆固醇治疗指南的新观点及其局限
§ EAS指南委员会对美国治疗胆固醇“新指南"相关评论的解读
§ 比较ACC/AHA与ESC/EAS血脂指南
§ 对2013年美国心脏病学学会/美国心脏协会胆固醇管理指南要点评述
§ 对2013年美国治疗血胆固醇降低成人动脉粥样硬化心血管疾病风险指南的思考、评论和质疑
§ 美国治疗胆固醇新指南带来的思考
§ 《美国居民膳食指南》放宽饮食胆固醇摄取入量的解读
§ 认真学习贯彻指南
血脂管理原则与实践
§ 国际动脉粥样硬化协会关于血脂异常管理的推荐要点
§ 关于我国当前血脂异常治疗的建议
§ 关于我国血脂异常与动脉粥样硬化性心血管病防控的一些思考
§ 坚持百年胆固醇学说 降低低密度脂蛋白胆固醇是硬道理
§ 降低密度脂蛋白胆固醇是硬道理
§ 关于血脂检验报告单参考值调整的建议
§ 从HPS2-THRIVE研究得到的启示
§ 高甘油三酯血症的防治进展
§ 急性冠状动脉综合征调脂治疗
§ 再议血脂相关性心血管剩留风险
§ 家族性高胆固醇血症治疗与治疗新进展
调脂药物的中国观点
§ 如何评价药物多效性
§ 非他汀类调脂药物应用地位评价
§ 大剂量他汀类药物临床应用的理性思考
§ 如何理解强化剂量他汀的证据和获益
§ 他汀类药物安全性再认识
Introduction

降胆固醇是硬道理
——从胆固醇学说到胆固醇定律
(代序)
1994年北欧的4S研究结果公布,揭开了他汀革命和他汀时代的序幕。人类在征服动脉粥样硬化性心血管病(ASCVD)的漫长征程中,第一次寻找到了通过降血胆固醇,可以稳定和逆转动脉粥样硬化斑块,减少ASCVD事件和ASCVD导致的死亡事件,减少ASCVD的急性发作,减少高成本和有创伤的血运重建手术,尤其是能降低全因死亡率的他汀类药物(简称他汀)。此后陆续完成的不同他汀常规剂量与安慰剂对照的随机临床试验(RCT),在ASCVD一级和二级预防中都取得了高度一致的阳性结果。并且与安慰剂对照,常规剂量他汀十分安全,不良事件的发生率甚至与对照组无明显差别。这些早期研究至今已有10~20年的随访数据,这些数据充分显示:早用他汀早获益;持续用他汀,长期获益。
随后出现了降胆固醇作用更强的阿托伐他汀和瑞舒伐他汀,在ASCVD防治的大多数领域,无论从伦理还是科学角度都无法再设计与安慰剂对照的RCT。因而制药企业与学术界合作启动了强化降胆固醇以更多获益的探索。而这些研究的结果并不一致,如同样针对急性冠脉综合征(ACS)的阿托伐他汀80mg/d对比普伐他汀40mg/d(相当于阿托伐他汀10mg/d)的研究结果阳性,而辛伐他汀大剂量与常规剂量对比的A to Z研究结果阴性;针对稳定性冠心病的阿托伐他汀80mg/d对比10mg/d的研究结果阳性,而阿托伐他汀80mg/d对比辛伐他汀40mg/d的研究结果阴性。但把相关研究进行荟萃分析,仍明确显示,把低密度脂蛋白胆固醇(LDL-C)降得更低一些,效果更好一些。强化策略针对的是高危人群,强化更多获益的原因是LDL-C下降水平的强化。但由于一些研究者的兴趣与制药企业的市场利益驱动,防治ASCVD的大方向被导向他汀降LDL-C之外的药物多效性,尤其是抗炎作用。在我国,制药企业把根本不是高质量RCT的小样本、短随访、软替代终点的一系列探索研究加以包装,以市场促销为目的,炮制了至今流毒很深的针对ACS与经皮冠状动脉介入治疗(PCI)围手术期的“序贯疗法”,其学术上的荒谬和临床上的危害就是从根本上否定了百年胆固醇学说,把个别他汀美化成一次突击大剂量就有抗炎奇效的“神药”。
2013年《美国心脏病学学会和美国心脏协会降低成人ASCVD风险胆固醇治疗新指南》(简称《ACC/AHA指南》)盲目推荐高强度大剂量他汀,取消LDL-C治疗目标,在学术界与临床实践中产生了更多困惑。一时间,防治ASCVD强化的是他汀剂量,而不再是LDL-C的目标水平。
2014年底公布的IMPROVE-IT研究结果,捍卫常识并丰富发展了百年胆固醇学说。我们今天应更理直气壮地强调:降胆固醇是硬道理。我很同意国际学术界对IMPROVE-IT的评价——将降胆固醇学说推进到胆固醇定律。
IMPROVE-IT开创了降LDL-C联合用药的新时代。IMPROVE-IT并未改变他汀临床用药的首要和主导地位,因为至今口服降胆固醇药物中他汀仍是最强的药物。依折麦布获取的是今日的“最佳配角奖”。但IMPROVE-IT结束了他汀一枝独秀和单打独斗的局面。他汀孤军奋战面临的挑战与局限是剂量倍增,降LDL-C疗效仅增6%;强化降胆固醇研究获阳性结果者均是他汀两个极端剂量的对比,即阿托伐他汀80mg/d与10mg/d的日剂量三次翻倍,使LDL-C下降的组间差别达18%左右才获取的。严重的问题是他汀所有严重不良反应都与大剂量相关。而且中国患者使用同等剂量,甚至中等剂量他汀时出现不良反应的概率是欧洲患者的10倍,而且程度更严重。
所有近期的国际指南都发表在IMPROVE-IT研究公布之前,因此,对联合用药的推荐力度很弱,甚至不推荐。并且推荐联合用药时,也把依折麦布与贝特类、烟酸、鱼油等传统老药并列。IMPROVE-IT的研究成果必将推动指南的重大修改。各种他汀的常规剂量,必要时联合依折麦布5~10mg/d是优化的降LDL-C达标方案。无论是18/50,还是50/18,这种联合用药都是更加有效的,而且安全和成本/效益合理。依折麦布是他汀的最佳搭挡。我们充满自信地推动在我国广泛使用联合用药策略,这有证据,是常识,也是临床用药的理性回归。
在我们出版的这本《中国胆固醇教育计划培训教材》的策划编写过程中,没有注重系统性,而特别强调针对性和临床实用性。针对国际、国内近期在这一领域出现的争议和混乱,更为及时地推动他汀与依折麦布的联合用药方案,更加旗帜鲜明地坚守百年胆固醇学说不动摇,与时俱进地推动胆固醇定律的落实,客观全面地介绍和评价他汀的安全性,消除对他汀降胆固醇以外的多效性的误解,努力消除荒谬的“序贯疗法”对我国临床的误导,推动中国ASCVD防控的规范化和现代化。
在这本教材中,我们突出强调要把国际的研究和指南与我国ASCVD防控的实践相结合。要努力学习和借鉴国际的研究成果与经验,但不能盲从,不能不加分析地照抄照办。要脚踏实地做好自己的工作,“穿中国鞋,走中国路,圆中国的健康梦”。
中华预防医学会?副会长
中国控制吸烟协会?会?长
中国心脏联盟?主?席 胡大一
2015年10月20日

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