New Insights on Reperfusion Choices Implications of STREAM. Paul W Armstrong MD

Transcription

1 New Insights on Reperfusion Choices Implications of STREAM ESC STEMI Satellite Symposium August Aligning Optimal Care to Time Place and Person Paul W Armstrong MD

2 Disclosure Statement Paul W. Armstrong MD Details Research Grants Boehringer Ingelheim sanofi aventis Eli Lilly GlaxoSmithKline Regado Biosciences Merck Consultant Regado Biosciences Astra Zeneca Data & Safety Monitoring Boards Roche Orexigen Eli Lilly Bayer 2014

3 STREAM STRATEGIC REPERFUSION EARLY AFTER MYOCARDIAL INFARCTION N Engl J Med 2013

4 Novel Insights from STREAM 2014 Role of PCI related delay Aborted MI / masquerade Aligning Infarct Size with Shock/CHF Understanding Rescue Implications of the amendment Elderly & TNK dosing Implications for Patient Care

5 STUDY AIM A strategy of early fibrinolysis followed by coronary angiography within 6-24 hours or rescue PCI if needed was compared with standard primary PCI in STEMI patients with at least 2 mm STelevation in 2 contiguous leads presenting within 3 hours of symptom onset and unable to undergo primary PCI within 1 hour. N Engl J Med online March 2013

6 PRIMARY ENDPOINT TNK vs PPCI Relative Risk 0.86, 95%CI ( ) Dth/Shock/CHF/ReMI (%) PPCI 14.3% TNK 12.4% p=0.24 a N Engl J Med online March 2013

7 Median Times To Treatment (Min) Sx onset 1st Medical contact Randomize IVRS TNK DANAMI 2 lysis 160 vs 188 for PCI Hospitals 28 min diff! min Sx onset 1st Medical contact Randomize IVRS 78 min difference PPCI n= Hour 2 Hours 178 min N Engl J Med 2013

8 STREAM Group A Aborted MI Baseline 90-min post TNK Pre-cath Baseline ECG Random ization TNK 90min post T ECG :22 12:33 12:40 14:11 11 July 2009

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10 Maleki et al Heart 2014 STREAM Aborted MI Study Population 1754 Group A, Pharmaco-invasive (893) Group B, Primary PCI (861) AbMI, (99) P <0.001 AbMI, (59)

11 AbMI Clinical Outcomes by Rx Group Maleki et al Heart 2014

12 Maleki et al Heart 2014 Aborted MI: Conclusions Rate AbMI sig higher for PI vs ppci (11.1 vs. 6.9%; p= 0.01) AbMI associated with: shorter time to 1st medical contact from Sx onset less extensive territory at risk i.e. smaller ΣSTdeviation at baseline lesser frequency baseline Q waves improved overall 30-day outcomes Improved outcomes with AbMI after PI Rx primarily related to lesser incidence shock & CHF Vigilance necessary to detect infarct masquerade (2.5%)

13 Infarct Masquerade 3.5 mm 3 mm Baseline ECG Random ization TNK 90 min Post TNK ECG Pre Cath ECG Rescue PCI Post Cath ECG Not done 153 Discharge ECG 03:23 04:06 04:20 05:44 05:45 06:53 08:40 15 Sep 10

14 SINGLE ENDPOINTS UP TO 30 DAYS Pharmaco-invasive PPCI P-value (N=944) (N=948) All cause death (43/939) 4.6% (42/946) 4.4% 0.88 Cardiac death (31/939) 3.3% (32/946) 3.4% 0.92 Congestive heart failure (57/939) 6.1% (72/943) 7.6% 0.18 Cardiogenic shock (41/939) 4.4% (56/944) 5.9% 0.13 Reinfarction (23/938) 2.5% (21/944) 2.2% 0.74 N Engl J Med online March 2013

15 MEDIAN TIMES TO TREATMENT (min) Sx onset 62 1st Medical contact Randomize IVRS 29 9 TNK 36% Rescue PCI at 2.2h 100 min 64% non-urgent cath at 17h Sx onset 1st Medical contact Randomize IVRS PPCI n= Hour 2 Hours 178 min N Engl J Med online March 2013

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17 Reperfusion Failure 6 mm 12 mm Baseline ECG Random ization TNK 90 min Post TNK ECG :40 08:51 08:51 10:28 22 Aug 2010

18 Reperfusion Succeeds: but Urgent PCI Required Baseline 90-min Pre-Cath Baseline ECG Random ization TNK 90 min Post TNK ECG Pre Cath ECG :57 20:14 20:30 22:00 23:25 29 July 2008

19 Median times to Rx (min) according to Rx received 99 min Rescue PCI Welsh et al AJC Rx TNK Scheduled PCI Sheath insertion Minutes min 1092 Sx onset 1st Medical contact Randomize IVRS Rx PPCI min a 1 Hour 2 Hours 3 Hours 4 Hours 19.9 Hours

20 Primary Endpoint by treatment received Dth/Shock/CHF/ReMI (%) Rescue vs Scheduled Log-Rank: p<0.001 Relative Risk 2.92, 95%CI ( ) PPCI vs Scheduled Log-Rank: p<0.001 Relative Risk 2.32, 95%CI ( ) Rescue 18.7% PPCI 13.9% Scheduled 5.5% Days since randomization Number at risk: Rescue: PPCI: Scheduled: a adjusted for the TIMI Risk Score for STEMI Welsh et al AJC 2014.

21 STUDY PROTOCOL STEMI <3 hrs from onset symptoms, PPCI <60 min not possible*, 2 mm ST-elevation in 2 leads RANDOMIZATION 1:1 by IVRS, OPEN LABEL Strategy A: pharmaco-invasive Strategy B: primary PCI Ambulance/ER <75y:full dose Aspirin Clopidogrel: LD 300 mg + 75 mg QD Enoxaparin: 30 mg IV + 1 mg/kg SC Q12h After 75y: 20% ½ dose of the TNK** planned recruitment, the TNK dose was reduced by 50% among patients 75 years Aspirin Clopidogrel: 75 mg QD Enoxaparin: 0.75 mg/kg of SC age. Q12h no lytic Antiplatelet and antithrombin treatment according to local standards PCI Hospital ECG at 90 min: ST resolution 50% YES angio >6 to 24 hrs PCI/CABG if indicated immediate angio + rescue PCI if indicated Standard primary PCI Primary endpoint: composite of all cause death or shock or CHF or reinfarction up to day 30 NO N Engl J Med online March 2013

22 São Paulo Problems and challenges in cardiovascular emergencies

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24 Reperfusion Paradox Implications Value Added Contributions Unintended Negative Consequences Enhanced coordination and collaborative support of hub-spoke model Greater focus on performance metrics with increased transparency across providers Increased emphasis on overcoming undertreatment Shorter times to PPCI in PCI-capable centres Persisting delays in accessing timely PCI in most patients presenting to non-pci hospitals Decline in ability to provide state of the art fibrinolytic management Proliferation of low-volume stand-alone PPCI centres Unnecessary coronary angiography or interventional procedures Diversion of patients from local community hospitals, with resultant potential for discontinuity of care and negative impact on long-term comprehensive secondary prevention

25 Questions have been raised about the overreliance on primary PCI for reperfusion, especially in the United States, and the unintended consequences that have evolved as familiarity with fibrinolysis has waned. The writing committee reiterates the principle highlighted in the 2004 ACC/AHA STEMI guideline, namely that the appropriate and timely use of some form of reperfusion therapy is likely more important than the choice of therapy. Greatest emphasis is to be placed on the delivery of reperfusion therapy to the individual patient as rapidly as possible. ACC/AHA STEMI Guidelines 2013

26 If the reperfusion therapy is primary PCI, the goal should be a delay (FMC to wire passage into the culprit artery) of 90 min In high-risk cases with large anterior infarcts & early presenters < 2 h, it should be 60 min) If reperfusion therapy is fibrinolysis, goal is to reduce this delay (FMC to needle) to 30 min.

27 Adapted Huber et al; STEMI Systems EHJ 2014 Preferred Approach to STEMI Care First wire passage of the IRA Door in/ out XPCI FMC to mechanical reperfusion (<120 min) If 120 min is not reliably achievable switch to fibrinolytic therapy Door / FMC to mechanical reperfusion (<90 min) Recommended maximal time delay in pts dirctly referred for PPCI Door/FMC to mechanical reperfusion (<60 min) Recommended time delay in pts with STEMI of <2 hrs duration FMC to pharmacological reperfusion (<30 min) Pharmacologic reperfusion occurs in 60-70% of patients within (45-60 min) Injection of lytic agent IRA reperfused

28 Reperfusion Decision-Making 2014 ppci is excellent Rx but efficacy declines if delay Ability to reliably achieve ppci difficult to predict Time from Sx onset is often imprecise: think baseline Q Dynamic Intersection between risk & time ~ efficacy If lysis given adjust dose in elderly : evaluate need rescue/urgent intervention especially in first few hours Develop nimble & versatile IT assisted pre hospital care system : keep both reperfusion options open Transfer high risk lytic pts to PCI centre using a well organized systems based approach(with frequent QA)

29 Let s Settle on Achieving Quality Incorporate what we know, measure what we do & investigate how we can do better Effective: Right drugs / procedures Timely: at right time Rapid Dx and treatment Safe: at right dose and done right Equitable: in all eligible pts Patient centered: considering the individual risks benefits, and values of this patient Cost-effective: and avoiding over-treatment IOM Definition