STREAM Trial Data Supports An Early Fibrinolysis-Based Strategy For Patients With STEMI Who Cannot Undergo Primary PCI
New data published in NEJM demonstrates that patients with STEMI who cannot undergo primary PCI within 60 minutes of first medical contact have similar clinical outcomes with early fibrinolysis with Metalyse® (tenecteplase, TNK-tPA) in combination with clopidogrel and enoxaparin, followed by timely angiography (pharmaco-invasive strategy), compared to patients given primary PCI after the 60-minute window.(1)
“In STEMI patients, the most important thing is to re-establish blood supply to the heart. Whilst the preferred option is primary PCI, the best strategy for reperfusion in patients who do not have access to timely PCI has been unclear. The STREAM study was set up to help answer this question” explained Co-principal STREAM(a) Investigator, Professor A. Gershlick, University of Leicester. “The results from STREAM confirm that patients who receive early fibrinolytic treatment followed by rescue angipoplasty or in-hospital angiography have a similar 30-day outcome to those receiving primary PCI, providing a therapeutic option for those patients who cannot receive primary PCI within guideline mandated times – for example because of geographical location or access to specialist centres.”
In STREAM, the primary composite endpoint of death, cardiogenic shock, congestive heart failure and reinfarction within 30 days was observed in 116 of 939 patients (12.4%) that received fibrinolysis, compared to 135 of 943 patients (14.3%) who received early primary PCI (relative risk in the fibrinolysis group 0.86 (0.68 – 1.09) p=0.21).(1)
Rates of fibrinolytic therapy use are falling in the UK, reflecting improvements in access to specialist Heart Attack Centres.2 In England in 2011/2012, 95% of patients who received any reperfusion treatment received primary PCI compared with 82% in 2010/11. In Wales the increase was from 30% to 50%. However, in some areas PCI rates are still significantly lower than national averages.(2) This is particularly true in hospitals with large rural catchment areas.
“The NHS has done extremely well in providing access to timely PCI for most patients in the UK; however, delays are still present in some areas due to geography and siting of Heart Attack Centres. Even in places with generally good access to PCI, traffic problems or adverse weather conditions can cause short-term issues with providing intervention within the recommended time frame” said Dr Chris Moulton, Consultant in Emergency Medicine, Royal Bolton Hospital. “This trial has important implications for the UK, especially if real-world outcomes bear out the study findings that a strategy based on early fibrinolysis is associated with comparable outcomes to waiting for primary PCI. Overall, this is a very interesting and exciting development in the field of reperfusion therapy for STEMI.”
According to Prof Tom Quinn, Associate Dean for Health and Medical Strategy, University of Surrey and member of the STREAM Trial Steering Committee, the study results provide an opportunity to build on paramedics’ experience of giving pre-hospital thrombolysis, to ensure that patients who cannot reach a heart attack centre within the target time benefit from the pharmaco-invasive approach.
“This study reinforces current guidelines, showing that while patients benefit from primary PCI as the preferred treatment if available in a timely fashion, there is still an important role for fibrinolysis in the treatment of STEMI” said Prof Quinn.
“The emphasis of treatment should always be on restoring blood flow in occluded arteries as quickly as possible, and when this cannot be quickly achieved through PCI, we should be looking to use thrombolysis followed by expert cardiological care, as part of a locally agreed pathway of care. Prior to PCI becoming first line treatment for STEMI, paramedics became highly proficient at administering fibrinolysis. We need to make sure that such skills are maintained as part of a network-wide approach, particularly in more rural geographies, with adequate support from hospital-based cardiology teams.”
STREAM (STrategic Reperfusion Early After Myocardial Infarction) is the first randomised, prospective exploratory study comparing a pharmaco-invasive strategy with primary PCI for patients with STEMI. STREAM is an open-label, prospective, randomised, parallel, comparative, international, multicentre exploratory trial to evaluate the outcome of prehospital patients presenting with a large ST-elevation myocardial infarction within 3 hours of symptom onset. Almost 2000 patients (n=1,892) were randomised to fibrinolysis with Metalyse® combined with enoxaparin, clopidogrel, and aspirin, followed by timely cardiac catheterization within 6 to 24 hours, or rescue coronary intervention if reperfusion failed within 90 minutes of fibrinolysis, versus primary PCI performed according to local standards.
STREAM excluded STEMI patients able to undergo primary PCI within 60 minutes of first medical contact(b).
The primary composite endpoint of death, cardiogenic shock, congestive heart failure and reinfarction within 30 days was observed in 116 of 939 (12.4%) of patients that received fibrinolysis, compared to 135 of 943 (14.3%) of patients who received early primary PCI (relative risk in the fibrinolysis group 0.86 (0.68 – 1.09) p=0.21).(1)
The study results revealed no significant treatment interactions. Cardiogenic shock (4.4% vs 5.9% p=0.13) and congestive heart failure (6.1% vs 7.6% p=0.18) occurred less frequently in the pharmaco-invasive patients, versus primary PCI group. For the other single clinical endpoints, namely all-cause mortality (4.6 % vs 4.4% p=0.88) and reinfarction (2.5% vs 2.2% p=0.74), the rates for pharmaco-invasive arm and primary PCI respectively, were similar.
The stroke rates (all types) were modest but strokes were significantly more frequent in the pharmaco-invasive arm (1.6% vs 0.5% p=0.03). There was no significant difference in the number of non-intracranial bleedings (6.5% in pharmaco-invasive arm vs 4.8% in major primary PCI, p=0.11).
Metalyse® (tenecteplase, TNK-tPA) is a fibrin clot dissolving drug indicated for the thrombolytic treatment of acute myocardial infarction (AMI). The efficacy of Metalyse® for the treatment of AMI has been demonstrated in approximately 20,000 patients treated with tenecteplase in monitored clinical studies (e.g. global ASSENT clinical trial programme). Metalyse® was licensed for use in the UK in February 2001. Boehringer Ingelheim is the Marketing Authorisation holder in all countries except USA, Canada and Japan. Metalyse®/TNKase® is currently authorised in 89 countries and is marketed in 86 of these.
Most cases of acute myocardial infarction are caused by disruption of an atherosclerotic plaque followed by coronary thrombosis. In ST-elevation myocardial infarction (STEMI), the thrombus occludes a major epicardial coronary artery. Such an occlusion is an emergency situation, and flow to the occluded vessel should be restored as soon as possible. Various strategies for reperfusion are available, namely mechanical reperfusion by primary percutaneous coronary intervention (primary PCI) or pharmacological reperfusion by fibrinolytic therapy.
a: STREAM (STrategic Reperfusion Early After Myocardial Infarction) study
b: First medical contact is defined as when ECG confirms STEMI
1. Armstrong PW, Gershlick AH, Goldstein P et al. Fibrinolysis or Primary PCI in ST-Segment Elevation Myocardial Infarction. NEJM 2013. DOI: 10.1056/NEJMoa1301092
2. Myocardial Ischaemia National Audit Project (MINAP). Annual Public Report. April 2011 to March 2012. Available at: https://www.ucl.ac.uk/nicor/audits/minap/publicreports/pdfs/2012minappublicreportv2
3. Huber K, Halvorsen S. The role of fibrinolysis in the era of primary percutaneous coronary intervention. Thromb Haemost 2011; 105: 390-395.