1、ACTION研究高血压亚组 结果与分析,稳定型心绞痛是冠心病最常见的临床表现，不仅明显影响患者的生活和工作能力，而且有高度发生各种心、脑血管病的危险。,稳定型冠心病的药物治疗现状,抗心绞痛硝酸酯类阻滞剂钙拮抗剂,改善病变进程抗血小板药他汀类ACEI,ACTION: 设计,ACTION: 基础治疗情况,ACTION: 终点事件,一级有效性终点,全因死亡致残性脑卒中心梗,一级安全性终点,1) 全因死亡，任何心血管事件或介入操作 (一级有效性终点 冠脉造影，PCI, CABG)2) 任何血管事件或介入操作: CV 死亡 急性MI 顽固性心绞痛 外周血管事件 致残性卒中 PCI CABG3) 任何心血
2、管事件(一级有效性终点 - 非CV 死亡),二级有效性终点,全因死亡 心梗 心衰 致残性脑卒中 顽固性心绞痛 外周血管重建术,ACTION: 分组,随机入组7,665名患者,7,661 名患者 进入亚组分析,4名患者被排除,3,977 名患者基线高血压,3,684 名患者基线血压正常,1,975名患者 拜新同组,2,002名 安慰剂组,ACTION：血压升高患者终点事件,终点,0.0150.0270.008,危险度(95% CI),p,0.873(0.7680.993)0.896(0.8120.998)0.832(0.7260.954),0,0.5,1,1.5,2,一级终点一级终点和介入治疗任
3、何CV原因导致的死亡,拜新同 更优,安慰剂 更优,ACTION: 高血压亚组结果,Overview of nifedipine GITS effects on composite endpoints,All patients,Hypertensive patients,Normotensive patients,Interaction between groups,Indicative implication,Primary efficacy,Not significant,Significant +ve benefit,Not significant,Significant,+ve bene
4、fit in hypertensives,Safety,Primary safety,Not significant,Not significant,Not significant,Not significant,Any CV event,Not significant,Significant +ve benefit,Not significant,Significant,+ve benefit in hypertensives,+ve benefit in all patients,Death, any CV event or procedure,Significant +ve benefi
5、t,Not significant,Significant +ve benefit,Significant +ve benefit,Any vascular event/procedure,Significant +ve benefit,Not significant,Endpoints,Significant +ve benefit,Significant +ve benefit,+ve benefit in all patients,临床意义(一),在已经实施降压治疗但血压依然升高的稳定性冠心病患者, 硝苯地平控释片(拜新同)能进一步有效地降低血压，显示拜新同与其它类型降压药联合治疗的协同
6、叠加作用，显著有益于冠心病患者的血压控制和达标。,EUROASPIRE and,冠心病合并高血压占冠心病患者51%(37%-64%)。 即使采用兼有降压作用的治疗冠心病药物，即-阻滞剂和ACEI，仍然有1/2以上患者血压未获得控制。 血压控制达标率EUROASPIRE (1995-1996): 44%EUROASPIRE (1999-2000): 45%,Boersma E, et al. J Hypertens 2003;21:1831-1840,ACTION(高血压亚组) 基线时降压药使用情况,ACTION(高血压亚组)：血压控制达标率,Nifedipine GITS reduced ad
7、d-on therapy in the hypertensive subgroup,*Including nifedipine GITS,6,3,0,3,6,9,12,15,18,21,-blockers ACE inhibitors/ARBs Diuretics Any antihypertensive*,Nifedipine GITS,Placebo,Normotensive,Nifedipine GITS,Placebo,Hypertensive,Change in add-on therapy from baseline (%),临床意义(二),稳定性冠心病合并高血压具有较高的心血管危
8、险, 硝苯地平控释片(拜新同)治疗能有效地阻止或减轻这类患者的病情进展, 并显著降低心脑血管病事件。 这种治疗益处来自拜新同有效降低血压和抗心绞痛的双重作用。,Mortality Due to CHD per Quartile of Usual Systolic and Diastolic BP: Seven Countries Study,van den Hoogen et al. N Engl J Med. 2000;342:1-8.,United States,Northern Europe,Mediterranean Southern Europe,Inland Southern Eu
9、rope,Serbia,Japan,Mortality From CHD (no./10,000 Person-Years),140,130,120,110,100,90,80,70,60,50,40,30,20,10,0,110,120,130,140,150,160,170,Systolic BP (mm Hg),140,130,120,110,100,90,80,70,60,50,40,30,20,10,0,65,70,75,80,85,95,100,Diastolic BP (mm Hg),90,动脉粥样硬化斑块,ACTION: 入选对象,有心绞痛症状占93%,患者的血管病变阶段,Hy
10、pertensive patients were at high risk of CVD,ACTION: 冠心病合并血压升高的心血管危险 (安慰剂组 /100人年),高血压 血压正常 高血压/血压正常心血管死亡 1.16 0.69 1.68心肌梗死 1.56 1.21 1.29心力衰竭 0.78 0.50 1.56脑卒中 1.81 0.97 1.87致残性脑卒中 0.77 0.26 2.96,BP-Lowering Treatment Trialists,Stroke,Systolic BP Difference Between Randomized Groups (mm Hg),Systol
11、ic BP Difference Between Randomized Groups (mm Hg),0.25,0.50,0.75,1.00,1.25,1.50,CHD,. Blood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.,RR of Outcome Event,RR of Outcome Event,0.6,0.8,1,1.2,1.4,Favours nifedipine GITS,Favours placebo,Significant reductions in co
12、mposite endpoints,NICOLE Study (Nisoldipine in Coronary Artery Disease in Leuven),Clinical event (%) Nisoldipine(408) Placebo(411) pDeath 2.9 3.4 NSCVA 1.0 1.7 NSAMI 3.9 3.2 NSCABG 5.1 10.0 0.01Repeat PTCA 30.6 37.7 0.03Total 44.6 52.7 0.02,Dens JA, et al. Heart 2003;89:887-892,临床意义(三),在稳定性冠心病合并高血压患
13、者, 硝苯地平控释片(拜新同)能显著降低需住院治疗的心力衰竭发生率, 首次在前瞻性临床试验中显示这种治疗益处。,Favors First Listed,Favors Second Listed,0.5,1.0,2.0,BP-Lowering Treatment Trialists Comparisons of Different Active Treatments,CA vs D/BB,1.33 (1.21, 1.47),1/0,0.93 (0.86, 1.01),CA vs D/BB,1/0,1.01 (0.94, 1.08),CA vs D/BB,1/0,ACE Inhibitor vs
14、CA,0.82 (0.73, 0.92),1/1,1.12 (1.01, 1.25),ACE Inhibitor vs CA,1/1,0.96 (0.88, 1.05),ACE Inhibitor vs CA,1/1,Stroke,CHD,1.09 (1.00, 1.18),ACE Inhibitor vs D/BB,2/0,0.98 (0.91, 1.05),ACE Inhibitor vs D/BB,2/0,1.07 (0.96, 1.19),ACE Inhibitor vs D/BB,2/0,Blood Pressure Lowering Treatment Trialists Coll
15、aboration. Lancet. 2003;362:1527-1535.,HF,BP-Lowering Treatment Trialists Comparisons of Active Treatments and Control,Nifedipine GITS prevents new overt heart failure,38%,Heart failure significantly reduced in patients with CHD Greater reduction in hypertensive subgroup Nifedipine GITS is the only
16、CCB proven to prevent heart failure,为何在ACTION研究中血压不升高的稳定性冠心病患者主要终点未获得显著降低？,问题与答案？, 大部分血压正常患者无降压效应,15,12,9,6,3,0,3,6,Placebo,Nifedipine GITS,Normotensive,BP change from baseline (mmHg),Systolic BP Diastolic BP,Nifedipine GITS,Placebo,Hypertensive,Significant mean change in BP after 4 years,ACTION: 拜新
17、同治疗过程中血压改变,治疗前 治疗过程中正常血压 122.3 / 74.6 (9.2/7.2) 1.9 / 0.5 (14.7/9.3)合并高血压 151.3 / 84.8 (14.0/8.6) 14.5 / 7.0 (18.2/10.0),15,10,5,0,100-109,120-129,180-189,140-149,150-159,Systolic,Diastolic,10,5,0,Pretreatment blood pressure (mmHg),60-69,70-79,80-89,90-99,100-109,110-119,Decrease in blood pressure (
18、treated - placebo) (mmHg),Law MR. BMJ 2003;326:1427,稳定型冠心病临床试验 基线血压水平,SBP(mmHg),HOPE EUROPA QUIET PEACE CAMELOT ACTION(血压不高亚组),139/79 137/82 123/74 134/78 129/78 122/75,结 论,ACTION研究确立了硝苯地平控释片(拜新同)在稳定性冠心病患者中的治疗地位，尤其合并血压升高患者，为合理选择抗心绞痛治疗药物提供了证据。,Short acting sublingual or buccal nitrate prn,Beta blocke
19、r,Add dihydropyridine calcium antagonist,Symptoms not controlled,Heart rate lowering calcium antagonist eg diltiazem/verapamil,Level of evidence,Long acting nitrate or transdermal nitrate,Immediate short term relief,Treatment aimed at relief of symptoms,Intolerant (eg fatigue) or contraindication,Intolerant or ineffective,Symptoms not controlled after dose optimisation,1C,1A,1A,1A,1B,1C,Guidelines for the management of stable angina,
