转换医学在冠心病治疗中的应用课件

转换医学在冠心病治疗中的应用转换医学在冠心病治疗中的应用 ThachThach Nguyen MD FACC FSCAI Nguyen MD FACC FSCAI Director of Cardiology Director of Cardiology St Mary Medical Center St Mary Medical Center Hobart IN USAHobart IN USA 定义定义: : 转换医学是由循证医学引领的可持转换医学是由循证医学引领的可持 续性的解决公共卫生问题的一个过程续性的解决公共卫生问题的一个过程 Lean MEJ, Mann JI, Lean MEJ, Mann JI, HoekHoek JA, Elliot RM and Schofield G. Translational Research: from JA, Elliot RM and Schofield G. Translational Research: from evidence-based medicine to sustainable solutions for public health problems. British Medical evidence-based medicine to sustainable solutions for public health problems. British Medical Journal 2008;337: a863 Journal 2008;337: a863 概概 述述 1. 基本评估： 决定性的思考 2. 研究结果向所有患者或所有药物的泛化性推广 3. 对将来相似性问题提供转换公式 4. 采用何种方式会是成功的？ 方法学问题方法学问题: : 选择的偏移选择的偏移 1. 男性女性 2. 年轻人老年人 3. 病人 vs 健康人 vs 病重患者 4. 随机，双盲 vs 回顾性 或注册研究 方法学问题方法学问题: :入选对象的数量入选对象的数量 小型试验（较低的死亡率）不可靠小型试验（较低的死亡率）不可靠 实用性：研究结果向所有患者或其他亚组实用性：研究结果向所有患者或其他亚组 人群的推广人群的推广 1.应用于所有患者 2.应用于亚组人群： 老人 年轻人 女性 少数民族 Why was Mortality So Low In GUSTO V?Why was Mortality So Low In GUSTO V? 7.4% 5.9% 10,1388,260 P女性 2. 年轻人老年人 3. 病人 vs 健康人 vs 病重患者 4. 随机，双盲 vs 回顾性 或注册研究 差异性的机制: 病人和病情较轻的病人 患者的随机化 (ITT) 女性, (%) 年龄 (年) 既往心梗病史 (%) 前壁心梗 (%) 糖尿病 (%) ASSENT II 97-98 16949 23 61 16 40 16 2.8 GUSTO V 99-01 16588 25 61 15 37 16 2.7 GUSTO III 95-97 15059 27 63 18 48 16 2.7 InTIME II 97-99 15060 25 62 16 42 14 2.9由出现症状到入选时的时间 （小时） GUSTO I 90-93 30647 25 62 17 39 15 2.8 数据的标准化：数据的标准化：若要降低若要降低1%1%的死亡率，的死亡率， TIMI 3TIMI 3级血流比例则需要增加级血流比例则需要增加20%20% The GUSTO Angiographic Investigators. N The GUSTO Angiographic Investigators. N EnglEngl J Med. 1993;329:1615-1622. J Med. 1993;329:1615-1622. 0 0 1010 2020 3030 4040 5050 6060 tPAtPASKSK % TIMI Grade 3 Flow% TIMI Grade 3 Flow 5 5 6 6 7 7 8 8 SKSK tPAtPA 54%54% 32%32% 6.3%6.3% 7.4%7.4% 数据的标准化数据的标准化: : 他汀绝对降脂转换为临床他汀绝对降脂转换为临床 获益获益 降低降低40 mg LDL = 40 mg LDL = 降低降低20%20%的血管事件风险的血管事件风险 = = 降低降低10%10%的全因死亡风险的全因死亡风险 这是相对降低风险，并非绝对-根据研究人群不同而 不同(风险越高，越需要绝对强化降脂). Zone A Zone B Zone E 脑血管 系统 肺系统 肾系统 上游 下游 程序布局 B 区 D 区 A 区 C 区 E 区 F 区 评估问题解答和调整程序的效果评估问题解答和调整程序的效果 1. 受体阻滞剂减少氧耗 (下游 C 区和全身 F 区) 2. 血管再生 (上游 C区) 3. 他汀 (病变区= A 区和全身F 区) 4. 心脏移植 = 置换硬件 (A区) 5. 增加型体外反搏 = (C区) (我怀疑这些结果) 6. 干细胞治疗梗死区域心肌细胞(C区) (我怀疑这些结果) Thank YouThank You Thank YouThank You Applications of Translational Applications of Translational Medicine (Randomized Clinical Medicine (Randomized Clinical Trials) in the Management of Trials) in the Management of Cardiovascular DiseaseCardiovascular Disease ThachThach Nguyen MD FACC FSCAI Nguyen MD FACC FSCAI Director of Cardiology Director of Cardiology St Mary Medical Center St Mary Medical Center Hobart IN USAHobart IN USA DEFINITION: Translational Medicine DEFINITION: Translational Medicine is the Process which Leads Evidence is the Process which Leads Evidence Based Medicine to Sustainable Based Medicine to Sustainable Solutions for Public HealthSolutions for Public Health Lean MEJ, Mann JI, Lean MEJ, Mann JI, HoekHoek JA, Elliot RM and Schofield G. Translational Research: from JA, Elliot RM and Schofield G. Translational Research: from evidence-based medicine to sustainable solutions for public health problems. British Medical evidence-based medicine to sustainable solutions for public health problems. British Medical Journal 2008;337: a863 Journal 2008;337: a863 Outline Outline 1. Basic assessment: Critical thinking 2. Generalization of the results to patients and class of drugs 3. Defining the formula for similar future problems 4. Which pathway will bring the success? Methodology Question: Biases in Selection Methodology Question: Biases in Selection 1. Men women 2. Young old 3. Sick vs Not Sick vs Too Sick 4. Randomized and Double Blinded vs retrospective or registry studies Methodology Question: Number of Events Methodology Question: Number of Events Practical Applications: Generalization Practical Applications: Generalization of the Results to all Patients or Subsetsof the Results to all Patients or Subsets Why was the Mortality So High in Why was the Mortality So High in GUSTO III?GUSTO III? 7.4% 5.9% 10,1388,260 P women 2. Young old 3. Sick vs Not Sick vs Too Sick 4. Randomized and Double Blinded vs retrospective or registry studies Mechanism of Difference: Sick and Not too Sick Patients Patients Randomized (ITT) Female, (%) Age (median years) Previous MI (%) Anterior MI (%) Diabetes (%) ASSENT II 97-98 16949 23 61 16 40 16 2.8 GUSTO V 99-01 16588 25 61 15 37 16 2.7 GUSTO III 95-97 15059 27 63 18 48 16 2.7 InTIME II 97-99 15060 25 62 16 42 14 2.9Median Time (hrs) Between Symptom and First Study Rx GUSTO I 90-93 30647 25 62 17 39 15 2.8 Standardization of the Data: Standardization of the Data: An 20% Increase An 20% Increase in TIMI 3 Flow is Needed to Yield a 1% in TIMI 3 Flow is Needed to Yield a 1% Mortality ReductionMortality Reduction The GUSTO Angiographic Investigators. N The GUSTO Angiographic Investigators. N EnglEngl J Med. 1993;329:1615-1622. J Med. 1993;329:1615-1622. 0 0 1010 2020 3030 4040 5050 6060 tPAtPASKSK % TIMI Grade 3 Flow% TIMI Grade 3 Flow 5 5 6 6 7 7 8 8 SKSK tPAtPA 54%54% 32%32% 6.3%6.3% 7.4%7.4% Formularization of a TrendFormularization of a Trend: : Absolute Absolute StatinStatin Reduction Translating into Clinical BenefitReduction Translating into Clinical Benefit 40 mg LDL decrease = 40 mg LDL decrease = 20% decrease in risk of 20% decrease in risk of vascular eventsvascular events = = 10% decrease in risk of 10% decrease in risk of total mortalitytotal mortality This is RELATIVE risk reduction, not absolute - that This is RELATIVE risk reduction, not absolute - that depends upon the study