No Advantage with Facilitated PCI Even in Patients Most Likely to Benefit

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Even the patients with acute myocardial infarction (AMI) most likely to benefit—those at high risk presenting early and with longer delays to the hospital—fail to derive any added benefit from facilitated compared with primary percutaneous coronary intervention (PCI), according to a study in the June 2011 issue of JACC: Cardiovascular Interventions.

For the LIPSIA-STEMI (Leipzig Immediate Prehospital Facilitated Angioplasty in ST-Segment Myocardial Infarction) trial, researchers led by Holger Thiele, MD, of the University of Leipzig-Heart Center (Leipzig, Germany), looked at 139 STEMI patients presenting within 3 hours of symptom onset in a regional network in Germany characterized by long hospital transfer distances. The patients were randomized to prehospital facilitated PCI (weight-adjusted tenecteplase) or primary PCI. Since the relative benefit of primary PCI is not as definitive in the early phase, it was thought that prehospital fibrinolysis may further aid in limiting infarct size.

All patients received aspirin, IV heparin, and clopidogrel. Patients in both groups were transported immediately to 1 of 3 hospitals with cath labs.

No Improvement Over Primary PCI

Most of the patients (72.3%) were from rural areas, and the median transport distance was 26.1 miles (42 km). Due to slightly longer treatment and transportation times with prehospital fibrinolysis, facilitated PCI patients had longer symptom-onset-to-first-balloon-inflation times than primary PCI patients (158 min vs. 131 min; P = 0.01), although door-to-balloon times were low in both groups (23 min vs. 25 min with primary PCI; P = 0.75).

Immediately prior to PCI, prehospital fibrinolysis resulted in higher percentages of TIMI flow grades 2 and 3 in the facilitated PCI group (26.6% and 44.3%, respectively) compared with the primary PCI group (10.3% and 24.4%; respectively; P < 0.001). However, post-stenting, the percentage of TIMI flow grade 3 in the infarct-related artery was similar in both groups (83.2% vs. 88.5% with primary PCI; P = 0.44).

Moreover, infarct size measured by cardiac MRI (primary endpoint) tended to be higher in the facilitated PCI group, as did early and late microvascular obstruction, while LVEF was equivalent (table 1).

Table 1. MRI Endpoints

Complete ST-segment resolution was also similar between the facilitated PCI group and the primary PCI group (42.9% vs. 57.7%; P = 0.18), as was the 30-day composite of death, reinfarction, and new congestive heart failure (19.8% vs. 13.6%; P = 0.13).

On multivariable analysis, reperfusion strategy had no effect on infarct size (P = 0.21).

“In an optimized STEMI network, prehospital initiated facilitated PCI does not add a benefit over primary PCI with respect to infarct size in STEMI patients presenting very early after symptom onset despite an earlier angiographic reperfusion and optimal antithrombotic comedication,” the researchers conclude, adding that “[t]he current study is in line with several large-scale trials showing that a facilitated approach as compared to primary PCI causes harm or is neutral at best.”

Study Authors Halt Use of Fibrinolysis in Practice

In an e-mail communication with TCTMD, Dr. Thiele said the results were counter to what had been expected. “The findings were surprising,” he said. “Our hypothesis was that the specific subgroup of patients presenting very early with relatively long transfer times in the prehospital setting would benefit from a facilitated PCI approach. This is exactly what we knew from subgroup analyses of the FINESSE and the ASSENT 4 PCI trials.”

The immediate ramifications of the findings are clear. “The practical implication for us is that we do not use fibrinolysis anymore,” Dr. Thiele said. “I believe that we should go in the direction of optimizing our networks. This is the most important issue. Organize your network and then you will not need fibrinolysis anymore.”

Why Didn’t It Work?

Dr. Thiele and colleagues offer numerous possible explanations for why prehospital tenecteplase may not have worked. For example, the patients may not have been high risk enough, or the trial’s open-label design may have led to a lower use of glycoprotein IIb/IIIa inhibitors (GPIs) in the facilitated PCI group (29% vs. 88%; P < 0.001), which in turn may have affected the outcomes. However, multivariable analysis showed that GPI use had no effect on infarct size (P = 0.34).

There also may have been another reason. “I believe that our network was too well organized and the times until first balloon inflation from medical contact were too fast,” Dr. Thiele said. “This is surprising given the long transfer distances. However, it is a clear sign that we can achieve the times that are recommended in guidelines.”

In an editorial accompanying the study, Bruce R. Brodie, MD, of the LeBauer Cardiovascular Research Foundation (Greensboro, NC), agrees that the delays to PCI in the study were much shorter than expected, with door-to-balloon times less than 90 minutes in the primary PCI group. “Allowing time to administer [tenecteplase] and time for [tenecteplase] to achieve reperfusion, the estimated times to reperfusion with facilitated PCI were no faster than with primary PCI,” he writes. “This appears to be the likely reason there was no improvement in infarct size with facilitated PCI.”

‘The Last Niche’?

According to Dr. Thiele, there may still be a group of patients likely to benefit from a facilitated approach. “We can only speculate on this,” he said. “There might be a group presenting very early with high risk and long transfer times that might benefit.”

According to Dr. Brodie, determining when the transfer time is long enough to warrant enrolling patients in a clinical trial is the trick. “Until that can be done, transfer for primary PCI, even with delays beyond 2 [hours], appears to provide the best reperfusion strategy for all but a small minority of patients,” he concludes.

Dr. Thiele agreed. “From my point of view, we tried to find the last niche for facilitated PCI. This is dead,” he said.

 

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Sources:
1. Theile H, Eitel I, Meinberg C, et al. Randomized comparison of pre-hospital-initiated facilitated percutaneous coronary intervention versus primary percutaneous coronary intervention in acute myocardial infarction very early after symptom onset: The LIPSIA-STEMI trial (Leipzig Immediate Prehospital Facilitated Angioplasty in ST-Segment Myocardial Infarction). J Am Coll Cardiol Intv. 2011;4:605-614.

2. Brodie BR. Facilitated percutaneous coronary intervention: Still searching for the right patients. J Am Coll Cardiol Intv. 2011;4:615-617.

 

 

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• Thrombus Burden May Explain Disadvantage of Facilitated PCI
• Similar 5-Year Mortality After Pre-Hospital Fibrinolysis vs. Primary PCI in STEMI
• FINESSE Published: Facilitated PCI No Improvement Over Primary PCI