ACTION研究高血壓亞組結(jié)果和分析

1、ACTION研究高血壓亞組結(jié)果和分析 穩(wěn)定型心絞痛是冠心病最常見(jiàn)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(xiǎn)。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(jìn)程 抗血小板藥 他汀類 ACEIACTION: 設(shè)計(jì)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

2、點(diǎn)事件一級(jí)有效性終點(diǎn) 全因死亡 致殘性腦卒中 心梗一級(jí)安全性終點(diǎn) 1) 全因死亡，任何心血管事件或介入操作 (一級(jí)有效性終點(diǎn) 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PCICABG3) 任何心血管事件 (一級(jí)有效性終點(diǎn) - 非CV 死亡) 二級(jí)有效性終點(diǎn)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(jī)入組7,665名患者7,661 名患者進(jìn)入亞組分析4名患者被排除3,977 名患者基線高血壓3,684 名患者基線血壓正常1,975名患者拜新同組2,002名安慰劑組1,847 名患者拜新同組1,

3、837名患者安慰劑組ACTION：血壓升高患者終點(diǎn)事件終點(diǎn)0.0150.0270.008危險(xiǎn)度(95% CI)p0.873(0.7680.993)0.896(0.8120.998)0.832(0.7260.954)00.511.52一級(jí)終點(diǎn)一級(jí)終點(diǎn)和介入治療任何CV原因?qū)е碌乃劳霭菪峦鼉?yōu)安慰劑更優(yōu)ACTION: 高血壓亞組結(jié)果單個(gè)終點(diǎn)減少一級(jí)有效終點(diǎn)13%證明拜新同安全性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10%減少任何血管或介入11% 血壓降低 14.6/7.6mmHg減少致殘性卒中33% 減少住院心衰38% 減少冠狀動(dòng)脈造影術(shù) 16%減少卒中或一過(guò)性腦缺血發(fā)作

4、28% 減少頑固性心絞痛23% *無(wú)統(tǒng)計(jì)學(xué)差異二級(jí)終點(diǎn)一級(jí)終點(diǎn)Overview of nifedipine GITS effects on composite endpointsAll patientsHypertensive patientsNormotensive patientsInteraction between groupsIndicative implicationPrimary efficacy Not significantSignificant+ve benefitNot significantSignificant+ve benefit in hypertensivesS

5、afetyPrimary safetyNot significantNot significantNot 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 benefit

6、Significant+ve benefitAny vascularevent/procedureSignificant+ve benefitNot significantEndpointsSignificant+ve benefitSignificant+ve benefit+ve benefit in all patients臨床意義(一) 在已經(jīng)實(shí)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(jìn)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(dá)標(biāo)。EUROASPIRE and冠心病合并高血壓占冠心病患者51%

7、(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(dá)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(shí)降壓藥使用情況 拜新同組安慰劑組-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(dá)標(biāo)率 基線時(shí)治療4年時(shí)BP 140/90 100%47%SBP

8、 140 94%45%DBP 90 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 GITSPlaceboHyperte

9、nsive Change in 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(xiǎn), 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(jìn)展, 并顯著降低心腦血管病事件。 這種治療益處來(lái)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.Unite

10、d StatesNorthern EuropeMediterranean Southern EuropeInland Southern EuropeSerbiaJapanMortality From CHD(no./10,000 Person-Years)1401301201101009080706050403020100110120130140150160170Systolic BP (mm Hg)1401301201101009080706050403020100657075808595100Diastolic BP (mm Hg)90動(dòng)脈粥樣硬化斑塊ACTION: 入選對(duì)象有心絞痛癥狀占

11、93%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

12、)65.1 (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(xiǎn)(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 Gr

13、oups (mm Hg)0.250.500.751.001.251.50-10-8-6-4-2024Systolic BP Difference Between Randomized Groups (mm Hg)0.250.500.751.001.251.50-10-8-6-4-2024CHD.Blood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.RR of Outcome EventRR of Outcome EventABCDEFGABCDEFG0.60.811.21.4F

14、avours nifedipine GITSFavours placeboSignificant reductions in composite endpointsEndpointPatients with events (n)Hazard ratio(95% CI)pNifedipine GITSPlaceboPrimary efficacy Normotensive Hypertensive3644393685000.02Primary safety Normotensive Hypertensive2443172133450.08Any CV event Normotensive Hyp

15、ertensive3173762864500.007Death, any CV event or procedure Normotensive Hypertensive6707687378460.8Any 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 N

16、S 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 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(yàn)中顯示這種治療益處。FavorsFirst ListedFavorsSecond Listed0.51.02.0BP-Lowering Treatment TrialistsComparisons

17、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/BB1/0 1.01 (0.94, 1.08) CA vs D/BB1/0 ACE Inhibitor vs CA 0.82 (0.73, 0.92)1/1 1.12 (1.01, 1.25) ACE Inhibitor vs CA1/1 0.96 (0.88, 1.05) ACE Inhibitor vs CA1/1StrokeCHD 1.09 (1.00, 1.18) ACE Inhibitor vs D/BB2/

18、0 0.98 (0.91, 1.05) ACE Inhibitor vs D/BB2/0 1.07 (0.96, 1.19) ACE Inhibitor vs D/BB2/0Blood Pressure Lowering Treatment Trialists Collaboration. Lancet. 2003;362:1527-1535.HFBP-Lowering Treatment TrialistsComparisons of Active Treatments and Control0.51.02.0Relative Risk RR (95% CI)BP DifferenceStr

19、oke 0.72 (0.64, 0.81) ACEI vs placebo-5/-2 0.62 (0.47, 0.82) CA vs placebo -8/-4Coronary heart disease 0.80 (0.73, 0.88)-5/-2 ACEI vs placebo 0.78 (0.62, 0.99)-8/-4 CA vs placebo ACEI vs placebo 0.78 (0.73, 0.83)-5/-2 CA vs placebo 0.82 (0.71, 0.95)-8/-4Heart failureMajor CV events-5/-2 0.82 (0.69,

20、0.98) ACEI vs placebo 1.21 (0.93, 1.58) CA vs placebo-8/-4CV mortality ACEI vs placebo 0.80 (0.71, 0.89)-5/-2 CA vs placebo 0.78 (0.61, 1.00)-8/-4Total mortality ACEI vs placebo 0.88 (0.81, 0.96)-5/-2 CA vs placebo 0.89 (0.75, 1.05)-8/-4Nifedipine GITS prevents new overt heart failure38%Heart failur

21、e significantly reduced in patients with CHDGreater reduction in hypertensive subgroupNifedipine GITS is the only CCB proven to prevent 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(diǎn)未獲得顯著降低？問(wèn)題與答案？ 大部分血壓正?；颊邿o(wú)降壓效應(yīng)1512963036PlaceboNifedipine GITS NormotensiveBP change from baseline (mmHg)Systolic BPDiast

22、olic BPNifedipine GITSPlaceboHypertensive Significant mean change in BP after 4 yearsACTION: 拜新同治療過(guò)程中血壓改變 治療前 治療過(guò)程中 正常血壓 122.3 / 74.6 (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