Thrombolysis with Immediate Transfer for PCI Safe for Rural STEMI Patients

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For patients with ST-segment elevation myocardial infarction (STEMI) who face a long delay to reach a center capable of performing primary percutaneous coronary intervention (PCI), half-dose fibrinolysis at the referral hospital followed by immediate transfer for PCI may be a safe, effective option, according to a registry study published online October 31, 2011, ahead of print in the European Heart Journal.

Investigators led by David M. Larson, MD, of Abbott Northwestern Hospital (Minneapolis, MN), analyzed outcomes for 2,634 consecutive STEMI patients in a prospective database who presented to either the PCI-capable Minneapolis Heart Institute or 1 of 31 referral hospitals throughout Minnesota and western Wisconsin between April 2003 and December 2009.

According to a standardized protocol, patients presenting to the PCI hospital received primary PCI (n = 600), as did those who presented to a community hospital within 60 miles of the PCI hospital and required transfer (n = 1,163). On the other hand, patients who presented to community hospitals 60 miles or more from the PCI center received a half-dose fibrinolytic (97% tenecteplase; 3% reteplase) followed by emergency transfer for immediate PCI (n = 660). In addition, some patients at less distant non-PCI hospitals received a half-dose fibrinolytic if  transfer was expected to be delayed.

Overall, 73.7% of patients received primary PCI as their main reperfusion therapy, while 26.3% received the pharmacoinvasive strategy. 

Pre-PCI patency (TIMI 2 or 3 flow) was found in 73.6% of patients given half-dose thrombolysis prior to transfer vs. 40.3% of those treated with primary PCI (P < 0.001). 

No Difference in Early Outcomes 

In a prespecified comparison, patients presenting directly to the PCI hospital had 30-day rates of mortality, stroke, recurrent ischemia/MI, and TIMI major bleeding similar to those of patients who presented to a distant hospital and received half-dose thrombolysis prior to transfer (table 1).

Table 1. Thirty-Day Outcomes: Direct Primary PCI vs. Pharmacoinvasive Strategy



Primary PCI Patients, Direct Presentation
(n = 600)

Pharmacoinvasive Patients, Distant Presentation
(n = 660)

P Value









Recurrent Ischemia/MI




TIMI Major Bleeding




The same pattern was seen when the comparison was broadened to include all primary PCI patients regardless of whether they presented directly to the PCI hospital or were transferred vs. all patients treated with the pharmacoinvasive strategy regardless of whether they presented to a nearby or distant non-PCI hospital (table 2).

Table 2. Thirty-Day Outcomes Primary PCI vs. Pharmacoinvasive Strategy



Primary PCI
(n = 1,763)

All Pharmacoinvasive Patients
(n = 692)

P Value









Recurrent Ischemia/MI




TIMI Major Bleeding




Kaplan-Meier estimates showed almost identical 1-year survival rates between patients treated with primary PCI and those treated with the pharmacoinvasive strategy.

The median length of stay was 3 days for both primary PCI and pharmacoinvasive patients; and there was no difference between any of the groups in the need for implantable cardiac defibrillators.

Of the 839 patients who presented to a hospital at least 60 miles from the PCI center, 179 were transferred for primary PCI without initial lytic therapy, mainly because fibrinolysis was contraindicated. With a median door-to-balloon time of 131 minutes, this group had higher in-hospital and 30-day mortality than patients who presented at distant hospitals and received a half-dose thrombolytic before transfer (9.5% vs. 5.3%; P = 0.039 and 10.6% vs. 5.6%; P = 0.17, respectively). However, the direct-transfer patients were older, had more risk factors, and were more likely to have experienced out-of-hospital cardiac arrest (11.7% vs. 7.0%; P = 0.037).

A Compromise Strategy for Rural Patients

According to Dr. Larson and colleagues, most cardiologists agree that the proven advantage of primary PCI over fibrinolysis decreases if arrival at a PCI-capable center is significantly delayed, with 30-day mortality rates rising as transfer times exceed 90 minutes.

In principle, a solution would combine the early availability of fibrinolysis with the improved reperfusion of PCI, the investigators say. Although early studies comparing versions of this strategy with primary PCI were disappointing, a meta-analysis of 3 more recent randomized trials—CARESS-in-AMI, TRANSFER-AMI, and NORDISTEMI—has demonstrated that routine early PCI after fibrinolysis in patients presenting to non-PCI hospitals reduces death and reinfarction at 30 days.

“Our data from real-world experience . . . are consistent with these randomized clinical trials and confirm the safety and efficacy of a pharmacoinvasive PCI strategy for rural STEMI patients in the USA who do not have timely access to primary PCI,” the authors write.

Optimal Anticoagulant Regimen, PCI Timing Uncertain

Although the timing of PCI following lysis is important, the optimal interval is unknown, the researchers note. In an e-mail communication with TCTMD, Dr. Larson said, “Earlier trials and subsequent guidelines have suggested that PCI should not be performed less than 3 hours after lysis. However, our data support the safety of performing PCI even as early as 60 minutes after lysis as the majority of our patients had PCI between 60 and 120 minutes post fibrinolysis.” An important factor, he added, is that transfer patients in the study had clopidogrel onboard for at least 60 minutes prior to PCI, giving them greater antiplatelet protection during the procedure and less risk of stent thrombosis.

Another unknown is the optimal pharmacologic regimen for STEMI patients who live too far away for primary PCI, Dr. Larson wrote. “We now have other antiplatelet drugs, such as prasugrel and ticagrelor, which may provide additional benefit and should be studied in this group of patients,” he observed.

As for why post-fibrinolysis patients were not simply monitored for ischemia after arrival at the PCI center, Dr. Larson said that was dictated in part by practical considerations. Waiting for angiography—the only sure way to know whether reperfusion has occurred—would result in further delay if the cath lab team then needed to be called in, he explained. “If [after angiography] there is still total occlusion of the culprit vessel (TIMI 0 or 1), then PCI is definitely indicated. If there is subtotal occlusion (TIMI 2 or 3 flow), why not perform PCI immediately if it is safe to do so rather than waiting till the next day and risking reinfarction during that interval?” he said.

Details aside, Dr. Larson concluded, “I cannot overemphasize how important it is to have an organized hub-and-spoke system in place in order for this [strategy] to be successful. All of the ‘spoke’ hospitals are trained and follow the same protocol. They also received ongoing feedback and participate in continuous quality improvement.”

The authors acknowledge that because of the time and resources required to develop such a system, their results may not be easily applicable. Nonetheless, they make a strong claim for the benefit of their approach. “Using a standardized protocol within a regional STEMI system of care, we have effectively eliminated urban-rural disparities in the treatment of STEMI,” they assert.

Study Details 

Pharmacoinvasive patients were somewhat older than primary PCI patients (63.2 ± 13.5 years vs. 61.8 ± 14.6 years; P = 0.025), but otherwise there were no differences in baseline clinical characteristics between the 2 groups. 

All patients received 325 mg of aspirin, 600 mg of clopidogrel, unfractionated heparin (60 U/kg IV load, 12 U/kg/h IV infusion) and a beta-blocker (unless contraindicated) in the emergency department of the presenting hospital.




Larson DM, Duval S, Sharkey SW, et al. Safety and efficacy of a pharmaco-invasive reperfusion strategy in rural ST-elevation myocardial infarction patients with expected delays due to long-distance transfers. Eur Heart J. 2011;Epub ahead of print.



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Thrombolysis with Immediate Transfer for PCI Safe for Rural STEMI Patients

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  • The study was supported by the Minneapolis Heart Institute Foundation.
  • Dr. Larson reports no relevant conflicts of interest.