Minneapolis and Rochester, MN - Two major PCI hospitals in Minnesota that successfully implemented ways of streamlining care of STEMI patients are proof that appropriate strategies can reduce door-to-balloon times, even for patients who first present to hospitals without PCI, new studies suggest [1,2]. But fibrinolysis played different roles in the two strategies, and the different approaches speak to the ongoing controversy over what constitutes the best care for STEMI patients in the US who present to community hospitals far from PCI centers.

The studies are published online in Circulation August 1, 2007.

In one paper, Dr Timothy D Henry (Abbott Northwestern Hospital, Minneapolis, MN) and colleagues describe the protocol they developed and implemented at 30 hospitals within 210 miles of the tertiary PCI center, Abbott Northwestern Hospital (ANH), between March 2003 and November 2006. In the protocol, all STEMI patients at the participating hospitals were transferred for PCI as swiftly as possible.

For 20 years everybody has always said you're supposed to have a standardized approach for treating STEMI . . . but when we started surveying all these hospitals, almost no one had them.

"We knew that European data showed that transfer worked well, so what we initially did was a survey of all the hospitals without cath labs," Henry told heartwire. "For 20 years everybody has always said you're supposed to have a standardized approach for treating STEMI, set out in the AHA/ACC guidelines, but when we started surveying all these hospitals, almost no one had them."

After first testing their standardized approach in a single pilot hospital, the group then expanded to 30 hospitals and report results on 1345 consecutive STEMI patients, of which 1048 were transferred from non-PCI hospitals. Outcomes and door-to-balloon times were then compared based on whether patients were within 60 miles of ANH (zone 1) or between 60 and 210 miles away (zone 2). According to their protocol, the emergency-department physician in the community hospital would activate the system with a single phone call that would initiate the transfer process to ANH. Protocols for patients in zones 1 and 2 were identical, except for the fact that zone 2 patients received half-dose tenecteplase unless contraindicated.

Overall, transfer times for the 421 zone 2 patients were longer than those for the 627 patients transferred within zone 1; still, 79% patients in zone 1 and 49% of patients in zone 2 achieved door-to-balloon times of less than 120 minutes (approximately 40% of zone 1 patients and 12% of zone 2 patients achieved times under 90 minutes). By comparison, more than 90% of the 297 patients presenting at the primary PCI hospital achieved door-to-balloon times under 120 minutes and more than 80% under 90 minutes. This is substantially better than times reported in recent National Registry of Myocardial Infarction (NRMI) data, the authors note, in which only 16% of transferred patients and 65% of patients at PCI hospitals had door-to-balloon times under two hours.

Strikingly, all three groups had similar rates of in-hospital and 30-day mortality. In all, five patients died before angioplasty was started (including four out-of-hospital cardiac arrests) and angioplasty was canceled in an additional five patients. Among the remainder, in-hospital, 30-day, and one-year mortality rates were low: 3.5%, 4.1%, and 6.4% respectively.

"These results are particularly notable because no patients were excluded from the analysis, including those with advanced age, cardiogenic shock, and out-of-hospital cardiac arrest," the authors conclude. " A standardized treatment approach to STEMI in the US has the potential to provide the optimal treatment (primary PCI) to the greatest number of patients, which will translate into improvement in the long-term outcome of STEMI patients."

Of note, the zone 2 patients, where a facilitated PCI approach was used, appeared to have equally favorable results, despite facing longer "in-door/out-door" times at the non-PCI hospitals—typically due to a longer wait for helicopter arrival—and longer transfer times.

To heartwire, Henry acknowledged that the "facilitated" component of the paper is likely to be "controversial" but points out that most studies that have looked at facilitated PCI have not included many, if any, patients on US soil.

"There are people who say that facilitated PCI doesn't work; I personally think that's a mistake. They base that on the ASSENT IV trial, but in ASSENT IV, more than 50% of the patients were in hospitals that had on-site PCI, they gave them full-dose lytics, and they did not allow Plavix or GP IIb/IIIa inhibitors. . . . As well, only 5% of the hospitals were in the US."

The case for primary PCI is clear-cut, Henry adds: people who present to PCI hospitals or who present at hospitals within 60 miles and can get treatment within 90 minutes should unequivocally get PCI. "But what about the situation where you have a long-distance transfer?" he asks. "The first choice is to give full-dose lytics and let the patient stay there. I think that's a mistake. The second choice is to do angioplasty alone, no matter how long it takes; I think that's a mistake, too." That leaves two other choices, he says. "One is to give full-dose lytics and transfer patients as part of an aggressive rescue policy; I think that's a very reasonable approach, but effectively what we're doing with our facilitated approach is what I call 'routine rescue.' Because we're essentially doing that with the half-dose plus clopidogrel. We are giving a lytic, and in our study 80% of those patients were open by the time they arrived at the hospital."

In the second study, Dr Henry H Ting (Mayo Clinic, Rochester, MN) and colleagues also report their experience with implementing a standardized STEMI protocol for patients presenting at both St Marys Hospital and 28 regional hospitals up to 150 miles away between May 2004 and December 2006. In all, 258 patients were treated with primary PCI at St Marys, while the remaining 236 presented to regional hospitals.

The standardized protocol put in place by Ting et al included many of the recommendations subsequently advocated in the ACC/AHA D2B initiative, previously reported by heartwire, for streamlining STEMI care. As Ting explained to heartwire, these were: emergency-department activation of the cath lab, a single call system to activate the cath-lab team, a commitment to having that cath lab fully operational within 30 minutes, and a timely, built-in feedback loop for staff.

Unlike the protocol used by Henry et al, Ting et al used the ACC/AHA guideline-recommended cutoff of three hours to determine whether patients presenting at non-PCI hospitals received lytics or were transferred. In all, 105 patients who presented at a regional hospital did so more than three hours after symptom onset and were transferred for PCI, while 131 who presented to a non-PCI hospital received full-dose fibrinolytic therapy. Of these last, 48 underwent transfer and immediate rescue PCI for suspected failure to reperfuse.

The authors report that median door-to-balloon time was 71 minutes for patients who presented at PCI hospitals and 116 minutes for those transferred from other hospitals. Median door-to-needle time for patients treated with fibrinolysis was 25 minutes. In-hospital deaths were similar for all three groups, ranging from 3.1% to 6.6%, while deaths at approximately six months ranged from 6.9% among patients who received thrombolytics to 10.5% among those treated with primary PCI after reporting to the PCI center.

"I think this really demonstrates and confirms the work of Betsy Bradley and Harlan Krumholz of what is achievable in a PCI center," Ting said, noting that median door-to-balloon time at St Marys had been around 90 minutes prior implementing the new protocol.

Ting also emphasized that the choice to treat patients with fibrinolysis is based on the class 1 recommendations of the current ACC/AHA guidelines. Mean transfer time from the non-PCI hospitals was 57 minutes, he noted, so the choice to treat patients who presented early with lytics is well-supported, with a rigorous protocol for rescue PCI when necessary. Moreover, all patients also underwent elective angiography and catheterization within 24 to 48 hours.

"DANAMI-2 and all the studies that showed primary PCI is better never actually included a pharmacoinvasive pathway of aggressive rescue PCI or elective PCI among those who have been reperfused," Ting argues. "All the patients who presented late or who were high risk and couldn't get thrombolytics we transferred for primary PCI and achieved what I think is a very good system. But the median door-to-balloon time in this group was 116 minutes—that's above the recommended 90-minute cutoff." In fact, he added only 12% of transfer patients achieved times less than 90 minutes, a number similar to that of Henry et al's zone 2 group.

"That's why we feel there is still a role for fibrinolytics in that setting," Ting said. He also emphasized that facilitated PCI is a class 2B indication. "So you're essentially foregoing two class 1 indicated treatments to do that," he said.

Both Henry and Ting emphasized to heartwire that the despite their different approaches, the message from the two studies should be that standardizing protocols in and across hospitals reduces delay times and leads to better patient outcomes.

"It's been an incredible thing," Henry said. "If you standardize care, and you make it a simple system, it's very clear to me that you can get very rapid door-to-balloon times, even over long distances."

Both our groups have shown what is possible to achieve.

Ting agreed. "I think the unique aspects of both papers are, whether you're in Minneapolis, MN or Rochester, MN, it is possible to integrate coordinated systems of care so that patients get faster treatment, either with fibrinolytics or angioplasty, with either protocol. That's to be applauded. Both our groups have shown what is possible to achieve."

Both also acknowledge that the best strategy for people who cannot undergo primary PCI remains unclear.

"Here's what I'd say," says Henry. "The appropriate treatment for people who have long-distance transfer is still unknown. So what we want to do is find the appropriate approach to those patients."

The problem, says Henry, is that randomized trials addressing the best approach for regional hospitals, spread out over long distances, are never going to happen. Data from Europe, where distances are much shorter, do not necessarily apply. "There is just no way in the US today that we could do a randomized trial in people who are long-distance transfer, because all these little, rural, community hospitals don't have the ability to randomize people into research trials," Henry said. "If you look at STEMI trials in the world today, it's woefully underrepresented by US patients."

Henry, for one, believes the facilitated-PCI story is not yet over and is buoyed by the fact that their study protocol has been adopted by other US centers where their door-to-balloon times and outcomes are comparable to those the authors are now reporting, even for patients traveling from farther afield. But Ting, by contrast, insists the guidelines support fibrinolysis for patients who would need to travel long distances, including the zone 2 group in Henry et al's trial. "The question is, would those patients in zone 2 be better off going straight to a PCI hospital or would they have been potentially better off with fibrinolytics? I think that's unknown."