从 timacs 研究结果再议 nsteacs 介入时机
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从 TIMACS 研究结果再议 NSTEACS 介入时机. 福建医科大学附属协和医院心内科 福建省冠心病研究所 陈良龙 MD PhD FACC. NSTE-ACS : Pathogenesis. Vulnerable Plague Not totally occlusive thrombosis White thrombus. Yeghiazarians Y, et al. N Engl J Med. 2000;342:101-114. 背景. 早期 尽早造影,明确病变,对后续治疗策略有指导意义; 减少等待期间不良事件的发生 [1] ; 缩短住院时间。 - PowerPoint PPT PresentationTRANSCRIPT
从 TIMACS 研究结果再议NSTEACS 介入时机
福建医科大学附属协和医院心内科福建省冠心病研究所
陈良龙 MD PhD FACC
NSTE-ACS : Pathogenesis Vulnerable
Plague
Not totally occlusive thrombosis
White thrombus
Yeghiazarians Y, et al. N Engl J Med. 2000;342:101-114.
背景 早期
尽早造影,明确病变,对后续治疗策略有指导意义; 减少等待期间不良事件的发生 [1] ; 缩短住院时间。
延迟 在积极抗血小板、抗凝、稳定斑块等治疗基础上,介入
治疗并发症少,安全系数更高 [2]; 等待期间可能发生不良事件乃至死亡 ; 延长住院时间 / 增加费用。
1.Neumann FJ, et al JAMA 2003;290:1593–9.2.Smith SC et al. Circulation 2001;103:3019–41.
目前指南 I 类推荐指征
UA/NSTEMI 患者 , 若有下列情况应早期介入 具有任何高危因素 病变适合 PCI 无影响 PCI 的严重合并症
问题与焦点 介入治疗的最佳时机尚不确定
早期:多早? 延迟:多长? 哪些患者需要尽早治疗?要多早?
目前的 RCT 研究结果不一致 [1,2] 。
1.Neumann FJ, et al JAMA 2003;290:1593–9.2. Riezebos RK, et al. Heart 2009;95:807-12.
Timing of Intervention in Patients with Acute
Coronary Syndromes (TIMACS)
Trial schema: TIMACS
UA/NSTEMI(3031)
Early Intervention( 1593 )
Delayed Intervention( 1438 )
angiographyafter 36 hrs ( 50h )
angiography within 24 hrs ( 14h )
Endpoint
Primary endpoint composite of death, MI, stroke at 6 m.
Secondary endpoints composite of death, MI, refractory ischemia
at 6m. composite of death, MI, stroke, refractory
ischemia, repeat revascularization at 6m.
End point HR (95% CI) p
Death, MI, stroke* 0.85 (0.68–1.06) 0.15
Death, MI, refractory ischemia
0.72 (0.58–0.89) 0.002
Death, MI, stroke, refractory ischemia, repeat intervention
0.84 (0.71–0.99) 0.039
Refractory ischemia
0.30 (0.17–0.53) <0.00001
Mehta SR, et al. N Engl J Med 2009;360:2165-75.
Primary and secondary outcomes in TIMACS, early vs delayed strategies
*Primary end point
Results: Primary endpoint
Results: Second endpoint
*Low/intermediate risk=GRACE score <140 High risk=GRACE score >140 *Prespecified analysis
Rates of death, MI, or stroke within six months according to GRACE score
Risk level by GRACE score*
Early (%)
Delayed (%)
HR (95% CI) p
Low/intermediate (n=2070)
7.7 6.7 1.14 (0.82–1.58) 0.43
High (n=961) 14.1 21.6 0.65 (0.48–0.88) 0.005
Kaplan–Meier Cumulative Risk of the Primary Outcome
High risk>140
Low-to- intermediate risk ≤140
High risk:>140; Low-to-intermediate risk: ≤140. ( GRACE Risk Score )
Stratified According to GRACE Risk Score
Conclusion
与延迟干预相比,早期干预对于 NSTE-ACS患者 6 个月不良事件发生率没有显著差异 ;
NSTE-ACS 患者接受早期干预安全性良好 ; 高危患者( GRACE 评分> 140 )可从早期
干预策略获益; 早期干预可显著减少 NSTE-ACS 患者再发
心绞痛的发生率,且不增加出血风险;
其他随机临床试验 ABOARD
ISAR-COOL
OPTIMA
Trial Flow: ABOARD
352 Pts randomized
175 Randomized to receive immediateangiography
177 Randomized to receive delayedangiography
175 Included in primary analysis 177 Included in primary analysis
Primary endpoint Peak troponin value during hospitalizationSecond endpointDeath, MI, urgent revascularization, or recurrent ischemia at 1m
Montalescot G, et al. JAMA 2009;302:947-54.
ABOARD 研究结果
ImmediateN=175
DeferredN=177
P
Time To CAG 1h+ (0.51-2.03)
21h (17.30-24.36)
Peak cTnI(ng/mL)
2.1 (0.3-7.1) 1.7 (0.3-7.2) 0.70
Endpoint(at 1 m)
21.1% 21.5% 0.94
Montalescot G, et al. JAMA 2009;302:947-54.
结论
对于 NSTE-ACS 患者 , 即刻( 1 小时)与延迟(次工作日)介入治疗策略比较 不能减少肌钙蛋白定义的 MI 不能减少 1 个月时的死亡、 MI 、紧急血运重建或 复发心肌缺血
Montalescot G, et al. JAMA 2009;302:947-54.
528 Pts Eligible
410 Randomized
203 early PCIReceive early intervention
207 Deferred PCIReceive Prolonged
Antithrombotic Pretreatment
Trial schema: ISAR-COOL
Endpoint: death, MI at 30d
ISAR-COOL 研究结果
EarlyN=203
DeferredN=207
P
Time To CAG < 6h 3-5 d
Endpoint(30d) 5.9%0 death12MI
11.6%3 death21MI
0.04RR 1.96
95%CI 1.01-3.82
Neumann FJ, et al JAMA 2003;290:1593–9.
This outcome was attributable to events occurring before catheterization;
after catheterization, both groups incurred 11 events each (P=.92).
结论
对于不稳定 ACS 患者 , 与早期介入治疗 +强化抗血小板比较, 延迟介入治疗 +延长抗栓治疗并不能改善临床
结局(死亡、 MI ), 相反地,后者在等待期增加了约 50%的事件。
Montalescot G, et al. JAMA 2009;302:947-54.
Trial schema: OPTIMA
251 NSTEACS Pts 142 R
Immediate(< 24h) PCI 73
Deferred(24-48h) PCI69
Endpoint: death, MI, at 30d and 6m
Riezebos RK, et al. Heart 2009;95:807-12.
OPTIMA 研究结果 *
ImmediateN=73
DeferredN=69
P
Time To CAG < 24h 24-48h
Endpoint(30d)
60% 39% 0.004
Endpoint(6m) 66% 43% 0.008
*No deaths occurred in either group
Riezebos RK, et al. Heart 2009;95:807-12.
结论
对于 NSTE-ACS 患者,与延迟介入治疗( 24-48H )比较: 尽管有强化的抗栓治疗,早期介入治疗( 24
H )还是增加 MI 对于非顽固 NSTE-ACS 患者,介入治疗至少应
延迟至入院后 24H进行
Montalescot G, et al. JAMA 2009;302:947-54.
4 RCTs总结n early deferred
TIMACS 3031 14h 50h
ABOARD 352 1h 21h -
ISAR-COOL 410 6h 3-5d +
OPTIMA 251 24 24-48h -
For Pts with high risk, too early or too late intervention is harmful. 24 h may be the proper time window in setting of intensive antithrombotic therapy
The Answers 多早?
在有效抗栓基础上, 约在入院后 24H,是早期 PC
I 的最佳窗口
哪些患者早做? 高危者 ( 包括血流动力学不
稳定 \ 恶性心律失常 ) 无禁忌者
感 谢!Fighting CVD
Reconsideration of Interventional
Therapeutic Time Window for NSTE-ACS
——Hint from the Result of TIMACS
Chen Lianglong MD, PhD, FACCCardiology, Union Hospital, Fujian Medical University
NSTE-ACS : Pathogenesis Vulnerable
Plague
Not totally occlusive thrombosis
White thrombus
Yeghiazarians Y, et al. N Engl J Med. 2000;342:101-114.
Background Early intervention might prevent ischemic events that c
ould occur while the pts are awaiting a delayed procedure.
Alternatively, by treating pts with intensive antithrombotic therapy and delaying intervention for several days, procedure-related complications might be avoided with intervention on a more stable plaque.
Current CLASS-I recommendations
An early invasive strategy is indicated for pts with UA/NSTEMI
who have any of the high-risk features & who have coronary lesions amenable to PC
I & who have no serious comorbidities.
Uncertain
the optimal timing of such intervention
remains controversial. Early strategy: how early
delayed strategy: how prolonged
Timing of Intervention in Patients with Acute
Coronary Syndromes (TIMACS)
Trial schema: TIMACS
UA/NSTEMI(3031)
Early Intervention( 1593 )
Delayed Intervention( 1438 )
angiographyafter 36 hrs
angiography within 24 hrs
Endpoint
Primary endpoint composite of death, MI, stroke at 6 m.
Secondary endpoints composite of death, MI, refractory ischemia
at 6m. composite of death, MI, stroke, refractory
ischemia, repeat revascularization at 6m.
End point HR (95% CI) p
Death, MI, stroke* 0.85 (0.68–1.06) 0.15
Death, MI, refractory ischemia
0.72 (0.58–0.89) 0.002
Death, MI, stroke, refractory ischemia, repeat intervention
0.84 (0.71–0.99) 0.039
Refractory ischemia
0.30 (0.17–0.53) <0.00001
Mehta SR, et al. N Engl J Med 2009;360:2165-75.
Primary and secondary outcomes in TIMACS, early vs delayed strategies
*Primary end point
Results: Primary endpoint
Results: Second endpoint
*Low/intermediate risk=GRACE score <140 High risk=GRACE score >140
Rates of death, MI, or stroke within six months according to GRACE score
Risk level by GRACE score*
Early (%)
Delayed (%)
HR (95% CI) p
Low/intermediate (n=2070)
7.7 6.7 1.14 (0.82–1.58) 0.43
High (n=961) 14.1 21.6 0.65 (0.48–0.88) 0.005
Kaplan–Meier Cumulative Risk of the Primary Outcome
High risk>140
Low-to- intermediate risk ≤140
High risk:>140; Low-to-intermediate risk: ≤140. ( GRACE Risk Score )
Stratified According to GRACE Risk Score
Conclusions
Early intervention did not differ greatly from d
elayed intervention in preventing the primary
outcome. but it did reduce the rate of the composite sec
ondary outcome of death, myocardial infarctio
n, or refractory ischemia
and was superior to delayed intervention in hi
gh-risk patients.
Other RCTs
ABOARD
ISAR-COOL
OPTIMA
Trial Flow: ABOARD
352 Pts randomized
175 Randomized to receive immediateangiography
177 Randomized to receive delayedangiography
175 Included in primary analysis 177 Included in primary analysis
Primary endpoint Peak troponin value during hospitalizationSecond endpointDeath, MI, urgent revascularization, or recurrent ischemia at 1m
Montalescot G, et al. JAMA 2009;302:947-54.
ABOARD-Results
ImmediateN=175
DeferredN=177
P
Time To CAG 1h+ (0.51-2.03)
21h (17.30-24.36)
Peak cTnI(ng/mL)
2.1 (0.3-7.1) 1.7 (0.3-7.2) 0.70
Endpoint(at 1 m)
21.1% 21.5% 0.94
Montalescot G, et al. JAMA 2009;302:947-54.
Conclusion
In pts with NSTE-ACS, a strategy of immediate intervention compared with a strategy of intervention deferred to the next working day (mean,21h) did not result in a difference in MI as defined by peak troponin level.
Montalescot G, et al. JAMA 2009;302:947-54.
528 Pts Eligible
410 Randomized
203 early PCIReceive early intervention
207 Deferred PCIReceive Prolonged
Antithrombotic Pretreatment
Trial schema: ISAR-COOL
Endpoint: death, MI at 30d
ISAR-COOL:Results
EarlyN=203
DeferredN=207
P
Time To CAG < 6h 3-5 d
Endpoint(30d) 5.9%0 death12MI
11.6%3 death21MI
0.04RR 1.96
95%CI 1.01-3.82
Neumann FJ, et al JAMA 2003;290:1593–9.
This outcome was attributable to events occurring before catheterization;
after catheterization, both groups incurred 11 events each (P=.92).
Conclusion
In pts with unstable coronary syndromes, deferred intervention for prolonged antithrombotic pretreatment does not improve the outcome compared with immediate ( early ) intervention accompanied by intense antiplatelet treatment.
Trial schema: OPTIMA
251 NSTEACS Pts 142 R
Immediate(< 24h) PCI 73
Deferred(24-48h) PCI69
Endpoint: death, MI, at 30d and 6m
Riezebos RK, et al. Heart 2009;95:807-12.
OPTIMA: Results*
ImmediateN=73
DeferredN=69
P
Time To CAG < 24h 24-48h
Endpoint(30d)
60% 39% 0.004
Endpoint(6m) 66% 43% 0.008
*No deaths occurred in either group
Riezebos RK, et al. Heart 2009;95:807-12.
Conclusions
Immediate PCI was associated with an increased rate of MI in comparison with a 24-48h deferred strategy, despite aggressive antithrombotic treatment.
The results suggest that PCI for high-risk patients with non-refractory NSTE-ACS should be delayed for at least 24h after hospital admission.
Riezebos RK, et al. Heart 2009;95:807-12.
Summary of RCTsn early deferred
TIMACS 3031 14h 50h
ABOARD 352 1h 21h -
ISAR-COOL 410 6h 3-5d +
OPTIMA 251 24 24-48h -
For Pts with high risk, too early or too late intervention is harmful. 24 h may be the proper time window
The Answers
How early? On aggressive anti-th
rombosis
24 h after hospital ad
mission
For Whom ? Pts with high risk
Pts suitable for PCI
感 谢!Fighting CVD