STREAM: First Success for Fibrinolysis Before Transport to PCI

March 10, 2013

SAN FRANCISCO, California — Fibrinolysis with tenecteplase and contemporary antithrombotic therapy given before transport to a PCI-capable hospital coupled with timely coronary angiography is as effective as primary PCI in STEMI patients presenting within three hours of symptom onset who cannot undergo primary PCI within one hour of first medical contact, the STREAM trial has shown.

There was a significant increase in intracranial hemorrhage (ICH) in the fibrinolysis group, which led to the dose of tenecteplase being halved in people aged 75 years and older fairly early on in the course of the trial, after which the intracranial hemorrhage rate in the fibrinolysis group was reduced to 0.5%, which was not significantly different from the PCI group.

Presenting the data here today at the American College of Cardiology 2013 Scientific Sessions, Dr Frans Van de Werf (University of Leuven, Belgium) said: "The results provide the opportunity for a measured approach to invasive coronary interventions, circumventing an urgent procedure in about two-thirds of fibrinolytic-treated STEMI patients." The study was also published online today in the New England Journal of Medicine [1].

Time to Consider Other Options

Van de Werf added: "Drug therapy before transfer is at least as effective as PCI, and an urgent catheterization was avoided in two-thirds of patients. This gives clinicians time to consider other options, such as CABG and medical therapy."

This is the first trial to have succeeded in showing that fibrinolysis given before transfer to a PCI hospital can be as effective as primary PCI, probably because it differs from other trials examining such a strategy in that patients were only given urgent PCI on arrival at the hospital if the ECG showed they had not reperfused. This avoided the situation of doing PCI with fibrinolysis on board (which has been associated with adverse outcomes in many trials of facilitated PCI) in two-thirds of patients.

Discussants of the study at the late-breaking clinical-trials session were enthusiastic about the findings. Dr Freek Verheugt (Nijmegen University, the Netherlands) said: "It is good that urgent procedures could be withheld for the majority of patients, as we know that off-hours emergency PCI has a worse outcome than daytime procedures. So this is good for the patients and relatives and for the interventional cardiologists and cath-lab staff. I think this study will change practice in certain parts of the world where there are long driving times to PCI hospitals."

Pharmacoinvasive Strategy Not Facilitated PCI

Dr George Dangas (Mount Sinai School of Medicine, New York, NY) made the point that this study should not be described as using "facilitated PCI", as most patients did not receive PCI soon after fibrinolysis. "This trial resembles more the design of the Transfer AMI study, in that after fibrinolysis is given, patients are transferred to the major PCI center without the decision being made for automatic immediate PCI on arrival." The strategy is referred to as "pharmacoinvasive" rather than "facilitated PCI."

Dangas added that the second message of the study is that patients over 75 years old or under 60 kg need different treatment--a lower fibrinolytic dose before transfer or faster transfer so that primary PCI can be performed.

Not Everyone Convinced

However, not everyone is enthralled with the STREAM results. In an editorial accompanying the published paper [2], Dr Deepak Bhatt (Brigham and Women's Hospital, Boston, MA) maintains that primary PCI is still the preferred treatment option [2].

He points out that there is still a risk of intracranial hemorrhage with the pharmacoinvasive approach and that since the start of the STREAM trial, several improvements have occurred in PCI that have led to results becoming better and safer, creating an even higher bar for prehospital fibrinolysis.

Bhatt concludes: "A pharmacoinvasive approach, including initial half-dose fibrinolysis in the elderly, may be an option in selected circumstances, though it does not represent optimal care as compared with timely primary PCI."

The trial involved 1915 STEMI patients from 15 countries who were first seen in community hospitals or by emergency medical personnel, and primary PCI was not possible until patients were transferred to a major medical center.

Before transfer, patients were randomized to PCI immediately after arrival or to tenecteplase plus enoxaparin, clopidogrel, and aspirin before arrival. Elderly patients had lower doses of clopidogrel (no loading dose) and enoxaparin.

When patients on tenecteplase reached a major medical center, 36% needed urgent PCI (decided by lack of ST resolution on ECG) and received it an average of 2.2 hours after randomization. The other 64% of patients did not need urgent PCI and received an angiogram an average of 17 hours after arrival and, based on the results, received PCI or CABG under nonurgent circumstances.

PCI at some point was performed in 90% of the PCI group vs 80% of the fibrinolysis group. CABG was performed in more patients in the fibrinolysis group (4.7% vs 2.1%).

The primary end point--a composite of all-cause mortality, shock, congestive heart failure, and subsequent heart attack at 30 days--were similar between the immediate-PCI and tenecteplase groups.

STREAM: Major Efficacy Results

Efficacy result Pharmacoinvasive (%) Primary PCI (%) p
All-cause death/shock/re-MI or CHF* 12.4 14.3 0.21
Death 4.6 4.4 0.88
Cardiac death 3.3 3.4 0.92
CHF 6.1 7.6 0.18
Cardiogenic shock 4.4 5.9 0.13
Re-MI 2.5 2.2 0.74
Rehospitalization for cardiac reason 4.8 4.3 0.64

*Primary end point

The end-point reduction in the pharmacoinvasive group was driven largely by heart failure and shock, which Van de Werf said were "important observations." He added: "They were not significant, but I think in view of the fact that we treat all patients very early with this strategy and it enables more patients to get bypass surgery, we might see an effect on long-term mortality."

It was also noted that patients with inferior MIs seemed to do better in the pharmacoinvasive arm, which Van de Werf said may possibly be explained by observations from previous studies suggesting that lytic therapy is more efficacious in recanalizing the right than the left coronary artery.

Van de Werf further pointed out that after the dosage amendment was made in the elderly, the primary end point almost reached significance in favor of the pharmacoinvasive group.

In terms of safety, there was a significant increase in intracranial hemorrhage in the pharmacoinvasive group before the reduced tenecteplase dose for the elderly was introduced. After that amendment, which was made after 20% of planned recruitment, intracranial hemorrhagic rates were similar between the groups.

STREAM: Stroke Data

Stroke result Pharmacoinvasive (%) Primary PCI (%) p
All strokes 1.6 0.5 0.03
ICH in total population 1.0 0.2 0.04
ICH after dosage amendment in elderly 0.5 0.3 0.45
Ischemic stroke 0.5 0.3 0.51

Other bleeding complications were not significantly different between the groups.

STREAM: Bleeding Results

Bleeding result Pharmacoinvasive (%) Primary PCI (%) p
Major non-ICH bleeding 6.5 4.8 0.105
Minor bleeding 21.8 20.2 0.395
Blood transfusion 2.9 2.3 0.473

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