Registry Study Examines Role of Fibrinolysis in STEMI Patients With Long Transfer Times

Only half of STEMI patients transferred from a community hospital to a primary PCI center achieve a door-to-balloon (D2B) time of less than 120 minutes when interhospital drive times exceed 30 minutes, according to a registry study published online December 8, 2014, ahead of print in JAMA: Internal Medicine. Moreover, among eligible patients with estimated transfer times of 30 to 120 minutes, fibrinolysis was associated with increased bleeding and no mortality advantage over PCI.Take Home: Registry Study Examines Role of Fibrinolysis in STEMI Patients With Long Transfer Times

“In the Unites States, neither fibrinolysis nor [primary PCI] is being optimally used to achieve guideline-recommended reperfusion targets,” write the authors. “For patients who are unlikely to receive timely [primary PCI], pretransfer fibrinolysis, followed by early transfer for angiography, may be a reperfusion option when potential benefits of timely reperfusion outweigh bleeding risk.”

Amit N. Vora, MD, MPH, of Duke University Medical Center (Durham, NC), and colleagues identified 22,481 STEMI patients eligible for primary PCI or fibrinolysis who were transferred from 1,771 referring centers to 366 STEMI-receiving centers in the Acute Coronary Treatment and Intervention Outcomes Network Registry-Get With the Guidelines database between July 2008 and March 2012. 

Lengthy Transfer Times Hinder Optimal Care

Overall, 29.5% of patients received fibrinolysis and the remainder were directly transferred for primary PCI. The median interhospital drive time was 57 minutes with a median interhospital distance of 48 miles. Drive times and distances were longer for patients who received pretransfer fibrinolysis compared with primary PCI. 

About half (51.3%) of STEMI patients who were directly transferred met the guideline-recommended D2B time of 120 minutes, but as the estimated driving time lengthened, fewer patients met this goal and more received fibrinolysis. For example, when the estimated driving time exceeded 60 minutes, only 29.6% of patients received primary PCI within 120 minutes and 52.7% received fibrinolysis.

In a secondary cohort of 15,437 fibrinolysis-eligible patients transferred to a center located between 30 and 120 minutes away, one-third received pretransfer fibrinolysis and two-thirds were directly transferred for primary PCI. Within the primary PCI group, only 43.7% achieved a D2B time less than 120 minutes. 

Among patients transferred to centers 30 to 120 minutes away, there were no differences in in-hospital mortality between patients who received fibrinolysis vs primary PCI (adjusted OR 1.13; 95% CI 0.94-1.36). However, the risk of in-hospital major bleeding was higher with fibrinolysis (adjusted OR 1.17; 95% CI 1.02-1.33), particularly among patients needing rescue PCI (adjusted OR 1.44; 95% CI 1.22-1.70). Intracranial hemorrhage was rare in both groups.

Overall, fibrinolysis-treated patients were slightly younger and had lower rates of diabetes and prior stroke compared with those who received primary PCI. Predicted in-hospital mortality risk was also slightly lower in the fibrinolysis group, as was the likelihood of cardiogenic shock at baseline. 

Additionally, median door-to-needle time for fibrinolysis patients was 34 minutes—only 43.8% received reperfusion within the 30-minute window. Tenecteplase was the most commonly used agent followed by reteplase, and 95.8% of patients received a full-dose. Median time from fibrinolytic administration to departure from the referring center was 46 minutes, and after transfer 97.1% underwent cardiac cath. Rescue PCI was performed in 41.5% of fibrinolysis-treated patients at a median time of 148 minutes.

Indecision, Reluctance May Hinder Fibrinolysis 

Although D2B times have decreased in recent years, “room for improvement remains in reperfusion performance in the United States because our study shows that neither fibrinolysis nor [primary PCI] is being optimally used to achieve guideline-recommended treatment targets,” Dr. Vora and colleagues write.

While their data do not capture causes for “care gaps” in fibrinolysis-eligible patients who fail to receive pretransfer treatment, “potential explanations may include indecision regarding reperfusion strategy, complex care coordination between STEMI-referring and -receiving centers, and reluctance to consider fibrinolysis,” they say. 

Driving time, the authors argue, should be more heavily factored into treatment decisions. They note that a forthcoming phase of the Mission: Lifeline geospatial information systems project “will prospectively designate statewide preferred reperfusion strategies to best meet current guideline benchmarks based on interhospital distance and transportation options.”

Nevertheless, they highlight the increased bleeding risk associated with fibrinolysis, observing that it “may be a reperfusion option for only a subset of patients deemed unlikely to receive timely [primary PCI].” 

Multiple Factors Tie Into Decision Making

In an editorial accompanying the story, Marc J. Claeys, MD, PhD, of Antwerp University Hospital (Edegem, Belgium), outlines 4 factors tied to selecting optimal reperfusion therapy if guideline-recommended timelines cannot be achieved:

  • Estimated system delay
  • Patient-related delay
  • Patient risk profile
  • Patient bleeding risk

“It is clear that clinical judgment remains the cornerstone in the selection of the optimal reperfusion therapy,” he writes. “However, fibrinolytic therapy should be primarily reserved for patients in whom we expect a pharmacoinvasive approach would be superior over [primary PCI]…. Additional research is needed to better define this subgroup, and large-scale studies such as that by Vora et al provide helpful pieces of this information.”

How Much Does Delay Matter? 

Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in an interview that the largest piece of information missing from the study is the number of patients who received fibrinolysis without being transferred. “That is completely against the guidelines, and we just don't know,” he said.

Evidently, Dr. Brener noted, “people think that primary PCI is much better regardless of the delay. There is something to it, but nevertheless the guidelines would indicate that these are good candidates for fibrinolysis. We need to sort out in our own minds whether delay to primary PCI is as important as we think it is.” 

If it turns out that the delay is in fact extremely important, then current practice needs to change, he said. But if the opposite is true, the guidelines should change. “Either way, we need to fix this,” Dr. Brener said, observing that the impact of a delay differs based on patient characteristics.


1. Vora AN, Holmes DN, Rokos I, et al. Fibrinolysis use among patients requiring interhospital transfer for ST-segment elevation myocardial infarction care: a report from the US National Cardiovascular Data Registry. JAMA Intern Med. 2014;Epub ahead of print.
2. Claeys MJ. Is primary percutaneous coronary intervention still the superior reperfusion strategy [editorial]? JAMA Intern Med. 2014;Epub ahead of print.

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  • This study was supported by the American College of Cardiology Foundation’s National Cardiovascular Data Registry and by the American Heart Association’s Mission: Lifeline program.
  • Drs. Vora, Claeys, and Brener report no relevant conflicts of interest.