ACTION研究高血壓亞組結(jié)果與分析

1、 穩(wěn)定型心絞痛是冠心病最常見的臨床表現(xiàn)，不僅明顯影響患者的生活和工作能力，而且有高度發(fā)生各種心、腦血管病的危險。穩(wěn)定型冠心病的藥物治療現(xiàn)狀抗心絞痛 硝酸酯類 阻滯劑 鈣拮抗劑改善病變進程 抗血小板藥 他汀類 ACEIACTION: 設(shè)計在冠心病基礎(chǔ)治療上加用安慰劑, 每天一次n=3,840在冠心病基礎(chǔ)治療上加用拜新同3060mg, 每天一次n=3,825012345年研究結(jié)束穩(wěn)定性心絞痛年齡 35 歲n=7,6656ACTION: 基礎(chǔ)治療情況 基線用藥情況(%) 患者(%) 抗心絞痛 99 降脂治療 68 阿司匹林 86 -受體阻滯劑 80ACTION: 終點事件一級有效性終點 全因死亡 致

2、殘性腦卒中 心梗一級安全性終點 1) 全因死亡，任何心血管事件或介入操作 (一級有效性終點 冠脈造影，PCI, CABG)2) 任何血管事件或介入操作: CV 死亡 急性MI 頑固性心絞痛 外周血管事件 致殘性卒中 PCI CABG3) 任何心血管事件 (一級有效性終點 - 非CV 死亡) 二級有效性終點全因死亡心梗心衰致殘性腦卒中頑固性心絞痛外周血管重建術(shù)ACTION: 分組隨機入組7,665名患者7,661 名患者進入亞組分析4名患者被排除3,977 名患者基線高血壓名患者基線高血壓3,684 名患者基線血壓正常1,975名患者名患者拜新同拜新同組組2,002名名安慰劑組安慰劑組1,847

3、 名患者拜新同組1,837名患者安慰劑組ACTIONACTION：血壓升高患者終點事件終點終點0.0.0150150.0270.0270.0080.008危險度危險度(95% (95% CI)CI)p p0.873(0.7680.873(0.7680.993)0.993)0.896(0.8120.896(0.8120.998)0.998)0.832(0.7260.832(0.7260.954)0.954)0 00.50.51 11.51.52 2一級終點一級終點一級終點和介入治療一級終點和介入治療任何任何CVCV原因?qū)е碌乃劳鲈驅(qū)е碌乃劳霭菪峦菪峦鼉?yōu)更優(yōu)安慰劑安慰劑更優(yōu)更優(yōu)ACTION:

4、 高血壓亞組結(jié)果單個終點單個終點減少一級有效終點減少一級有效終點13%證明拜新同安全性證明拜新同安全性減少任何心血管事件減少任何心血管事件17% 減少全因死亡，任何心血管事件和介入治療減少全因死亡，任何心血管事件和介入治療10%減少任何血管或介入減少任何血管或介入11% 血壓降低血壓降低 14.6/7.6mmHg減少致殘性卒中減少致殘性卒中33% 減少住院心衰減少住院心衰38% 減少冠狀動脈造影術(shù)減少冠狀動脈造影術(shù) 16%減少卒中或一過性腦缺血發(fā)作減少卒中或一過性腦缺血發(fā)作28% 減少頑固性心絞痛減少頑固性心絞痛23% *無統(tǒng)計學(xué)差異二級終點二級終點一級終點一級終點Overview of ni

5、fedipine GITS effects on composite endpointsAll patientsHypertensive patientsNormotensive patientsInteraction between groupsIndicative implicationPrimary efficacy Not significantSignificant+ve benefitNot significantSignificant+ve benefit in hypertensivesSafetyPrimary safetyNot significantNot signifi

6、cantNot significantNot significantAny CV eventNot significantSignificant+ve benefitNot significantSignificant+ve benefit in hypertensives+ve benefit in all patientsDeath, any CV event or procedureSignificant+ve benefitNot significantSignificant+ve benefitSignificant+ve benefitAny vascularevent/proce

7、dureSignificant+ve benefitNot significantEndpointsSignificant+ve benefitSignificant+ve benefit+ve benefit in all patients臨床意義(一) 在已經(jīng)實施降壓治療但血壓依然升高的穩(wěn)定性冠心病患者, 硝苯地平控釋片(拜新同)能進一步有效地降低血壓，顯示拜新同與其它類型降壓藥聯(lián)合治療的協(xié)同疊加作用，顯著有益于冠心病患者的血壓控制和達標(biāo)。EUROASPIRE and 冠心病合并高血壓占冠心病患者51%(37%-64%)。 即使采用兼有降壓作用的治療冠心病藥物，即-阻滯劑和ACEI，仍然有

8、1/2以上患者血壓未獲得控制。 血壓控制達標(biāo)率 EUROASPIRE (1995-1996): 44% EUROASPIRE (1999-2000): 45% Boersma E, et al. J Hypertens 2003;21:1831-1840ACTION(高血壓亞組)基線時降壓藥使用情況基線時降壓藥使用情況 拜新同組拜新同組安慰劑組安慰劑組-阻滯劑 77%79%ACEI/ARB 28%28%利尿劑 15%14%任何降壓藥 88%88%ACTION(高血壓亞組)：血壓控制達標(biāo)率 基線時基線時治療治療4 4年時年時BP 140/90 100%47%SBP 140 94%45%DBP 9

9、0 42%13% SBP (mmHg) 14.6 19.1 DBP (mmHg) 7.6 10.6Nifedipine GITS reduced add-on therapy in the hypertensive subgroup *Including nifedipine GITS63036912151821 -blockers ACE inhibitors/ARBs Diuretics Any antihypertensive* Nifedipine GITS PlaceboNormotensive Nifedipine GITSPlaceboHypertensive Change in

10、 add-on therapy from baseline (%)臨床意義(二) 穩(wěn)定性冠心病合并高血壓具有較高的心血管危險, 硝苯地平控釋片(拜新同)治療能有效地阻止或減輕這類患者的病情進展, 并顯著降低心腦血管病事件。 這種治療益處來自拜新同有效降低血壓和抗心絞痛的雙重作用。Mortality Due to CHD per Quartile of Usual Systolic and Diastolic BP: Seven Countries Studyvan den Hoogen et al. N Engl J Med. 2000;342:1-8.United StatesNorther

11、n EuropeMediterranean Southern EuropeInland Southern EuropeSerbiaJapanMortality From CHD(no./10,000 Person-Years)1401301201101009080706050403020100120130140150160170Systolic BP (mm Hg)1401301201101009070605040302010657075808595100Diastolic BP (mm Hg)90動脈粥樣硬化斑塊動脈粥樣硬化斑塊ACTION: 入選對象有心絞痛癥狀占有心絞痛癥狀占93%93%

12、患者的血管病變階段Risk factorNormotensive(n=3,684)Hypertensive(n=3,977)pCurrent smoker (%)20160.001Total cholesterol 5mmol/L (%)61660.001Body mass index 30kg/m2 (%)19260.001Any of the above (%)73770.001Diabetes mellitus (%)12170.001Treated with insulin (%)22.70.04Mean (SD) heart rate (beats/min)63.5 (10.0)65

13、.1 (10.5)0.003Hypertensive patients were at high risk of CVDACTION: 冠心病合并血壓升高的心血管危險(安慰劑組 /100人年) 高血壓 血壓正常 高血壓/血壓正常 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 腦卒中 1.81 0.97 1.87 致殘性腦卒中 0.77 0.26 2.96BP-Lowering Treatment TrialistsStrokeSystolic BP Difference Between Randomized Group

14、s (mm Hg)Systolic BP Difference Between Randomized Groups (mm Hg)CHDBlood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.RR of Outcome EventRR of Outcome Event0.60.811.21.4Favours nifedipine GITSFavours placeboSignificant reductions in composite endpointsEndpointPati

15、ents with events (n)Hazard ratio(95% CI)pNifedipine GITSPlaceboPrimary efficacy Normotensive Hypertensive3644393685000.02Primary safety Normotensive Hypertensive2443172133450.08Any CV event Normotensive Hypertensive3173762864500.007Death, any CV event or procedure Normotensive Hypertensive6707687378

16、460.8Any vascular event or procedure Normotensive Hypertensive4795465116100.7NICOLE Study(Nisoldipine in Coronary Artery Disease in Leuven) Clinical event (%) Nisoldipine(408) Placebo(411) p Death 2.9 3.4 NS CVA 1.0 1.7 NS AMI 3.9 3.2 NS CABG 5.1 10.0 0.01 Repeat PTCA 30.6 37.7 0.03 Total 44.6 52.7

17、0.02Dens JA, et al. Heart 2003;89:887-892臨床意義(三) 在穩(wěn)定性冠心病合并高血壓患者, 硝苯地平控釋片(拜新同)能顯著降低需住院治療的心力衰竭發(fā)生率, 首次在前瞻性臨床試驗中顯示這種治療益處。FavorsFirst ListedFavorsSecond Listed0.51.02.0BP-Lowering Treatment TrialistsComparisons of Different Active TreatmentsCA vs D/BB1.33 (1.21, 1.47)1/00.93 (0.86, 1.01)CA vs D/BB1/01.01

18、 (0.94, 1.08)CA vs D/BB1/0ACE Inhibitor vs CA0.82 (0.73, 0.92)1/11.12 (1.01, 1.25)ACE Inhibitor vs CA1/10.96 (0.88, 1.05)ACE Inhibitor vs CA1/1StrokeCHD1.09 (1.00, 1.18)ACE Inhibitor vs D/BB2/00.98 (0.91, 1.05)ACE Inhibitor vs D/BB2/01.07 (0.96, 1.19)ACE Inhibitor vs D/BB2/0Blood Pressure Lowering T

19、reatment Trialists Collaboration. Lancet. 2003;362:1527-1535.HFBP-Lowering Treatment TrialistsComparisons of Active Treatments and Control0.51.02.0Relative RiskRR (95% CI)BP DifferenceStroke0.72 (0.64, 0.81ACEI vs placebo-5/-20.62 (0.47, 0.82)CA vs placebo 8/-4Coronary heart disease0.80 (0.73, 0.88)

20、-5/-2ACEI vs placebo0.78 (0.62, 0.99)-8/-4CA vs placeboACEI vs placebo0.78 (0.73, 0.83)-5/-2CA vs placebo0.82 (0.71, 0.95)-8/-4Heart failureMajor CV events-5/-20.82 (0.69, 0.98)ACEI vs placebo1.21 (0.93, 1.58)CA vs placebo-8/-4CV mortalityACEI vs placebo0.80 (0.71, 0.89)-5/-2CA vs placebo0.78 (0.61,

21、 1.00)-8/-4Total mortalityACEI vs placebo0.88 (0.81, 0.96)-5/-2CA vs placebo0.89 (0.75, 1.05)-8/-4Nifedipine GITS prevents new overt heart failure38%lHeart failure significantly reduced in patients with CHDlGreater reduction in hypertensive subgrouplNifedipine GITS is the only CCB proven to prevent

22、heart failure 為何在ACTION研究中血壓不升高的穩(wěn)定性冠心病患者主要終點未獲得顯著降低？問題與答案？ 大部分血壓正?；颊邿o降壓效應(yīng)1512963036PlaceboNifedipine GITS NormotensiveBP change from baseline (mmHg)Systolic BPDiastolic BPNifedipine GITSPlaceboHypertensive Significant mean change in BP after 4 yearsACTION: 拜新同 治療過程中血壓改變 治療前 治療過程中 正常血壓 122.3 / 74.6 (

23、9.2/7.2) 1.9 / 0.5 (14.7/9.3) 合并高血壓 151.3 / 84.8 (14.0/8.6) 14.5 / 7.0 (18.2/10.0) 151050100-109120-129180-189140-149150-159SystolicDiastolic1050Pretreatment blood pressure (mmHg)60-6970-7980-8990-99 100-109 110-119Decrease in blood pressure (treated - placebo) (mmHg)Law MR. BMJ 2003;326:1427穩(wěn)定型冠心病臨

24、床試驗基線血壓水平基線血壓水平SBP(mmHg)HOPEEUROPAQUIETPEACECAMELOTACTION(血壓不高亞組)139/79137/82123/74134/78129/78122/75結(jié) 論 ACTION研究確立了硝苯地平控釋片(拜新同)在穩(wěn)定性冠心病患者中的治療地位，尤其合并血壓升高患者，為合理選擇抗心絞痛治療藥物提供了證據(jù)。Short acting sublingualor buccal nitrate prn Beta blockerAdd dihydropyridinecalcium antagonistSymptoms not controlledHeart rat

25、e loweringcalcium antagonist eg diltiazem/verapamilLevel of evidenceLong acting nitrate ortransdermal nitrateImmediate short term reliefTreatment aimed atrelief ofsymptomsIntolerant (eg fatigue)or contraindicationIntolerantor ineffectiveSymptoms not controlled after dose optimisation 1C1A1A1A 1B1CGu

26、idelines for the management of stable angina穩(wěn)定型冠心病的藥物治療現(xiàn)狀抗心絞痛 硝酸酯類 阻滯劑 鈣拮抗劑改善病變進程 抗血小板藥 他汀類 ACEIACTIONACTION：血壓升高患者終點事件終點終點0.0.0150150.0270.0270.0080.008危險度危險度(95% (95% CI)CI)p p0.873(0.7680.873(0.7680.993)0.993)0.896(0.8120.896(0.8120.998)0.998)0.832(0.7260.832(0.7260.954)0.954)0 00.50.51 11.51.52

27、2一級終點一級終點一級終點和介入治療一級終點和介入治療任何任何CVCV原因?qū)е碌乃劳鲈驅(qū)е碌乃劳霭菪峦菪峦鼉?yōu)更優(yōu)安慰劑安慰劑更優(yōu)更優(yōu)EUROASPIRE and 冠心病合并高血壓占冠心病患者51%(37%-64%)。 即使采用兼有降壓作用的治療冠心病藥物，即-阻滯劑和ACEI，仍然有1/2以上患者血壓未獲得控制。 血壓控制達標(biāo)率 EUROASPIRE (1995-1996): 44% EUROASPIRE (1999-2000): 45% Boersma E, et al. J Hypertens 2003;21:1831-1840Mortality Due to CHD per Quartile of Usual Systolic and Diastolic BP: Seven Countries Studyvan den Hoogen et al. N Engl J Me