从REAL-CAD研究,看中等强度他汀治疗的亚洲人群获益

从REAL-CAD研究，看中等强度他汀治疗的亚洲人群获益REAL-CAD研究简介为匹伐他汀在亚洲患者中使用提供了新的证据•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.高剂量VS.低剂量匹伐他汀对日本稳定性冠状动脉疾病患者的随机优势试验REAL-CAD研究设计研究目的：一项前瞻性、多中心（733家中心）、随机、开放标签、盲终点试验，旨在评估与低剂量匹伐他汀相比，符合指南推荐的高剂量匹伐他汀是否可减少日本稳定性冠脉疾病患者的不良心血管事件。纳入标准：研究纳入20-80岁稳定性冠脉疾病患者13054例，稳定性冠脉疾病定义为：急性冠状动脉综合征（ACS）或冠状动脉血运重建史（PCI/CABG）＞3个月；冠状动脉造影结果显示冠脉狭窄程度至少为75%；导入期给予匹伐他汀1mg/d，导入期后患者LDL-C120mg/dl入选；导入期后随机分组为匹伐他汀1mg/d组和4mg/d组，随访36-60个月。匹伐他汀1mg/day签署知情同意书随机分组匹伐他汀1mg/d组n=6528匹伐他汀4mg/d组n=65262010.01~2013.052016.01-03LDL-C＜120mg/dL导入期（＞1个月）随访期（36-60个月）•IntHeartJ.2018Mar30;59(2):315-320.doi:10.1536/ihj.17-557.Epub2018Mar5.研究患者配置情况纳入14774例患者2010.01~2013.03，733家日本中心导入期后，13054例患者进行随机化分组排除1720例退出/丢失知情790例其他原因930例匹伐他汀1mg组（6528例）匹伐他汀4mg组（6526例）退出/丢失知情100例退出/丢失知情136例安全性数据集（SAS）6428例安全性数据集（SAS）6390例不符合入选标准214例ACS发病＜3个月35例LDL-C100mg/dL未接受他汀治疗76例随机化时LDL-C≥120mg/dL105例不符合入选标准191例ACS发病＜3个月16例LDL-C100mg/dL未接受他汀治疗76例随机化时LDL-C≥120mg/dL101例全数据集（FAS）6214例全数据集（FAS）6199例随访周期[中位]：3.9（0-5.9年）5809例（96.9%）完成1年随访5451例（94.3%）完成2年随访4793例（89.8%）完成3年随访截止2016年1月份，5169例（83.2%）完成最终随访随访周期[中位]：3.9（0-5.8年）5607例（97.0%）完成1年随访5250例（94.0%）完成2年随访4608例（89.7%）完成3年随访截止2016年1月份，5171例（83.4%）完成最终随访•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.基线特征（略表）变量匹伐他汀1mg组(N=6,214)匹伐他汀4mg组(N=6,199)Age—years68.1±8.368.0±8.3Malesex83%83%BMI—kg/m224.6±3.424.6±3.3Hypertension75%76%Diabetesmellitus40%40%Currentsmoking16%17%HistoryofACS72%72%ACSwithin1yearbeforerandomization24%24%Coronaryrevascularization91%90%Revascularizationwithin1yearbeforerandomization28%28%Ischemicstroke7%7%Peripheralvasculardisease7%7%CKD(eGFR60mL/min/1.73m2)36%35%Aspirin93%92%DAPT45%44%Statinsbeforeenrollment91%91%•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.REAL-CAD研究结果：脂质参数和hs-CRP的变化TGYears6,208125.41mg6,032125.55,606122.35,245122.44,507121.56,195127.14mg5,896117.55,498115.05,183114.54,402114.5Baseline0.5123No.ofPatientsMaineffectp0.001Interactionp=0.770110115120125130TG(mg/dL)HDL-CYears1mg4mg6,21250.76,02850.65,59651.65,23851.64,49851.76,19850.75,89051.05,48252.25,17452.34,38852.3Baseline0.5123Maineffectp0.001Interactionp=0.17No.ofPatients0505152535455HDL-C(mg/dL)hs-CRPMonths1mg4mg6,0320.595,7340.595,9940.575,5850.49Baseline6No.ofPatients00.450.500.550.600.65hs-CRP(mg/L)Maineffectp0.001LDL-CBaseline0.51Years236,21488.11mg6,03189.45,61591.15,25291.14,50991.06,19987.74mg5,89073.75,51875.55,20376.64,40576.6Pitavastatin1mgMaineffectp0.001Interactionp0.001Pitavastatin4mgNo.ofPatients7007580859095100LDL-C(mg/dL)16%•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.REAL-CAD研究结果：主要终点（CVdeath/MI/Ischemicstroke/UA）匹伐他汀1mg匹伐他汀4mg6,2146,1995,7435,6315,321Years5,2564,5014,4272,7602,730593616NumberatriskCumulativeincidence(%)246804.25.61.41.23.52.32.94.6012345HR0.81(95%CI,0.69-0.95)P=0.01匹伐他汀1mg匹伐他汀4mg•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.4mg匹伐他汀治疗组的主要终点事件发生率显著低于1mg匹伐他汀治疗组REAL-CAD研究结果：次要终点（主要终点+冠脉重建）8.010.42.82.56.74.75.88.5201816141286421005,6605,5565,1665,1314,3274,2772,6272,617561588Cumulativeincidence(%)匹伐他汀1mg匹伐他汀4mgNumberatrisk0123456,2146,199YearsHR0.83(95%CI,0.73-0.93)P=0.002:ExcludingTLRforlesionstreatedatpriorPCI*匹伐他汀1mg匹伐他汀4mg•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.4mg匹伐他汀治疗组的次要终点事件发生率显著低于1mg匹伐他汀治疗组REAL-CAD研究结果：其他次要终点发生事件的数目(%)Outcomes1mg(n=6,214)全因死亡心血管死亡心肌梗死缺血性卒中出血性卒中不稳定性心绞痛需入院治疗冠脉重建（所有）冠脉重建（靶病变血管再生）冠脉重建（靶病变血管再生）4mg(n=6,199)260(4.2)112(1.8)72(1.2)83(1.3)30(0.5)90(1.4)626(10.1)356(5.7)319(5.1)207(3.3)86(1.4)40(0.6)84(1.4)43(0.7)76(1.2)529(8.5)277(4.5)276(4.5)HR(95%CI)PValue0.81(0.68-0.98)0.78(0.59-1.04)0.57(0.38-0.83)1.03(0.76-1.40)1.46(0.92-2.33)0.86(0.63-1.17)0.86(0.76-0.96)0.79(0.68-0.92)0.88(0.75-1.03)0.030.090.0040.840.110.340.0080.0030.1214mgBetter1mgBetter•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.REAL-CAD研究结果：亚组分析（主要终点）SubgroupNo.ofpatientsEventrate(%)1mgHR(95%CI)Pvalueforinteraction总体年龄性别糖尿病LDL-Chs-CRPHDL-CTG体重指数（BMI）65≥65MaleFemaleYesNo95mg/dL≥95mg/dL1mg/L≥1mg/L≤40mg/dL40mg/dL150mg/dL≥150mg/dL25≥2512,4134,0098,40410,2532,1604,9787,4357,8654,5488,5103,5162,6079,8038,0454,3586,6934,7885.45.05.65.73.86.54.65.05.94.96.76.55.15.15.95.35.74.33.34.84.63.04.84.04.04.83.66.05.04.14.34.24.54.40.81(0.69-0.95)0.67(0.49-0.91)0.87(0.72-1.05)0.81(0.68-0.96)0.81(0.51-1.28)0.75(0.59-0.95)0.86(0.69-1.08)0.81(0.66-1.00)0.81(0.63-1.05)0.75(0.61-0.92)0.89(0.68-1.16)0.78(0.56-1.08)0.82(0.68-0.99)0.86(0.70-1.06)0.73(0.56-0.96)0.87(0.70-1.07)0.78(0.60-1.00)0.160.990.390.970.320.780.340.5314mg4mgBetter1mgBetter•Circulation.2018May8;137(19):1997-2009.doi:10.1161/CIRCULATIONAHA.117.032615.REAL-CAD研究结果：安全性结果事件匹伐他汀1mg(N=6,428)匹伐他汀4mg(N=6,390)Pvalue不良事件—N(%)横纹肌溶解1(0.0)2(0.0)0.62肌肉问题45(0.7)121(1.9)0.001新发糖尿病279(4.3)285(4.5)0.76实验室测试异常率—N(%)ALT,AST升高,或二者≥3ULN174(2.7)187(2.9)0.46CK升高≥5ULN40(0.6)42(0.7)0.83研究药物停药—N(%)503(8.1)610(9.8)0.001•Circulation.2018May8;137(19):1997-2009.doi:10