March 10th, 2013
Fibrinolysis May Benefit Late-Arriving STEMI Patients
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Although primary PCI has emerged as the best treatment for STEMI, most patients don’t receive this treatment within the early time frame when it is known to be most beneficial. Delay in presentation is one important factor. Another is that most patients don’t arrive at a PCI-capable hospital and cannot be transferred fast enough to a PCI hospital.
The STREAM (Strategic Reperfusion Early after Myocardial Infarction) trial was planned as a proof-of-concept study to assess whether fibrinolysis was a beneficial alternative in this difficult group. Results were presented at the ACC in San Francisco and published simultaneously in the New England Journal of Medicine.
A total of 1892 STEMI patients with symptoms lasting less than three hours and unable to receive primary PCI within 1 hour were randomized to either primary PCI or fibrinolytic therapy with tenectaplase, clopidogrel, and enoxaparin. Fibrinolysis patients underwent angiography at 6 to 24 hours or, if fibrinolysis was unsuccessful, immediately.
The primary endpoint — the composite of death, shock, CHF, or reinfarction at 30 days — occurred in 12.4% of the fibrinolysis group versus 14.3% of the primary PCI group (RR, 0.86; 95% CI, 0.68-1.09; P=0.21). There was no significant difference in overall bleeding.
Overall, there were significantly more intracranial hemorrhages in the fibrinolysis group (1.0% vs. 0.2%; P=0.05). However, when the early excess of intracranial hemorrhage in elderly patients was observed, after about one-fifth of patients in the trial had been enrolled, the tenectaplase dose was cut in half for patients 75 years of age or older. After this change, the rate of intracranial hemorrhage was not significantly higher in the fibrinolysis group (0.5% vs. 0.3%; P=0.45).
More than a third of patients (36.3%) in the fibrinolysis group underwent emergency angiography. The median time from symptom onset to initiation of reperfusion therapy was 100 minutes in the fibrinolysis group compared with 178 minutes in the primary PCI group.
The investigators said that although the trial was not designed to demonstrate noninferiority, the results fell within the “generally accepted” margins for noninferiority:
On the basis of our findings, applied post hoc, the 95% confidence interval of the relative risk of the primary end point in the fibrinolysis group would exclude a relative increase of 9% (or an absolute increase of 1.1 percentage points), as compared with the primary PCI group. Although our study did not prespecify noninferiority boundaries, it is noteworthy that generally accepted proportional margins for noninferiority trials currently fall in the range of 15 to 20%.
In an ACC press release, lead investigator Frans Van de Werf said:
“Drug therapy before transfer is at least as effective as [angioplasty], and an urgent catheterization was avoided in two-thirds of patients. It gives [clinicians] time to consider other options, such as [coronary artery bypass graft] and medical therapy.”