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STREAM: Early Fibrinolytic Strategy Safe at 1 Year When Timely Primary PCI is Unattainable

By L.A. McKeown

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In patients with ST-segment elevation myocardial infarction (STEMI) who cannot undergo timely primary percutaneous coronary intervention (PCI), guideline-recommended fibrinolytic therapy results in effective reperfusion and comparable rates of mortality at 1 year, according to updated findings from the STREAM trial published online August 26, 2014, ahead of print in Circulation.

The findings were first presented in November 2013 at the American Heart Association Scientific Sessions in Dallas, TX.

Methods 
STREAM (Strategic Reperfusion Early After Myocardial Infarction) included patients from 99 institutions in 15 countries who presented within 3 hours of symptom onset and were unable to undergo primary PCI within 1 hour of medical contact.
Patients were randomized to either primary PCI (n = 948) or fibrinolytic therapy with bolus tenecteplase (half dose in patients aged 75 years and older, amended midway through the study due to risk of ICH; n = 944) before transport to a PCI-capable hospital from March 19, 2008, to September 7, 2012. Tenecteplase was administered in a weight-based dose and combined with enoxaparin, aspirin, and clopidogrel according to current guidelines. Urgent coronary angiography in the pharmacoinvasive arm was permitted at any time if hemodynamic or electrical instability, worsening ischemia, or progressive or sustained ST-elevation developed.
For the new study, Frans Van de Werf, MD, PhD, of University Hospitals Leuven (Leuven, Belgium), and colleagues analyzed available 1-year mortality data from STREAM participants.

Mortality Low and Similar

Rates of all-cause and cardiac death were similar for both treatment strategies (table 1). Overall, there were 7 cardiac deaths in each treatment arm, with an excess of 6 noncardiac deaths in the pharmacoinvasive arm.

Table 1. Mortality at 1 Year

 

Pharmacoinvasive

(n = 944)

Primary PCI

(n = 948)

P Value

All-Cause Mortality

6.7%

5.9%

.49

Cardiac Mortality

4.0%

4.1%

.93

Rates of all-cause mortality also were similar among the prespecified subgroups, with the exception of randomization before amendment of the tenecteplase protocol. Prior to the amendment, mortality was higher with the pharmacoinvasive strategy than with primary PCI (9.9% vs 4.3%; P = .031), whereas the curves for both arms converged after the amendment (5.9% vs 6.3; P = .71). In contrast, no such differences were seen in cardiac mortality.

The study authors suggest that the relatively short treatment delays in both arms might partly explain the lack of difference in mortality and note that in a real-world setting, fibrinolytics “could lead to a greater clinical benefit compared to transfer for primary PCI, given the typically longer PCI-related delays.” However, they note, the STREAM results do not apply to patients able to undergo primary PCI within 1 hour after first medical contact, those who present more than 3 hours after symptom onset, or those treated with other fibrinolytic agents.

“Taken together, our 1-year findings support the current 120-minute guideline-recommended maximum tolerable delay overall for transfer to primary PCI, as well as the shorter time window of 60 minutes for high-risk patients presenting early,” the authors write. “Our results indicate that if these time windows cannot be met, a [pharmacoinvasive] strategy as used in STREAM is likely to be as good as [primary] PCI.”

Equivalence of Fibrinolytics Not Proven

However, in an editorial accompanying the study, Eric R. Bates, MD, of the University of Michigan Medical Center (Ann Arbor, MI), stresses that STREAM does not prove that a fibrinolytic strategy is equivalent to primary PCI, but rather “adds more evidence to support the conclusion that a fibrinolytic strategy including early coronary angiography is an excellent therapy for STEMI when primary PCI is not readily available, especially in patients with potentially large myocardial infarct size or when early treatment is possible.”

STREAM is important, he notes, because it used the pharmacoinvasive strategy recommended by current practice guidelines. Dr. Bates questions why the study authors fail to include the 1-year composite primary endpoint and the other secondary endpoint results (shock, heart failure, reinfarction) in the new report, but applauds their efforts to amend the tenecteplase protocol, noting that while 3 ICH events occurred in patients aged 75 years and older prior to the amendment, there were no cases once the risk was recognized and the dose was halved.

“Although efficacy has not been proven, safety is paramount in this age group, so fibrinolytic treatment protocols should emphasize these dose reductions for tenecteplase, clopidogrel, and enoxaparin in patients ≥ 75 years of age,” Dr. Bates writes. “Hopefully, this will encourage the treatment of more elderly patients who have previously been denied the potential benefits of reperfusion therapy because of the real concern about the increased risk for ICH.”

The study authors note that a formal recommendation regarding tenecteplase dosing “awaits further analyses from this trial as well as future studies to come.”

 

Sources:
  1. Sinnaeve PR, Armstrong PW, Gershlick AH, et al. STEMI patients randomized to a pharmaco-invasive strategy or primary PCI: the STREAM 1-year mortality follow-up. Circulation. 2014;Epub ahead of print.
  2. Bates ER. The evolution from fibrinolytic therapy to a fibrinolytic strategy for patients with ST-segment elevation myocardial infarction [editorial]. Circulation. 2014;Epub ahead of print. 

Disclosures:

  • The STREAM study is funded by Boehringer Ingelheim.
  • Dr. Van de Werf reports receiving grants, consultancy fees, travel, and lecture fees from Boehringer Ingelheim.
  • Dr. Bates reports no relevant conflicts of interest.

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