As COVID-19 Spreads, US Cath Labs Ponder Fibrinolytics for STEMI

Business as usual may not be possible, and overwhelmed hospitals may consider lytic-based pathways, a group says.

As COVID-19 Spreads, US Cath Labs Ponder Fibrinolytics for STEMI


(UPDATED) The varying severity of COVID-19 “surges” around the United States to date has left cath labs debating whether to switch to fibrinolytic-based strategies for STEMI patients, or continue to offer primary PCI. The former has proven inferior in clinical trials, but the latter may expose physicians, patients, and staff to a higher risk of infection, and may not be feasible in hospitals overwhelmed by the pandemic, where critical cardiovascular staff have been redeployed to assist with the crisis.

The dilemma got new fodder this week in the form of a perspective published in Circulation. In it, Matthew Daniels, MRCP, PhD (Manchester Heart Center, England), and colleagues argue that a fibrinolytic-based strategy for STEMI patients may be a “reasonable consideration” for fast reperfusion at a time when “a blanket policy of primary PCI for all STEMI patients may be hard to both justify and operationally deliver,” particularly in the setting of limited hospital resources.

“In caring for our patients, we must recognize that optimal care strategies, established outside the challenges of a pandemic, may be potentially suboptimal during it,” they write. “These are challenging and unprecedented times, and we should not pretend that we can provide business as usual.”

In March, the American College of Cardiology (ACC) Interventional Council and the Society for Cardiovascular Angiography and Interventions (SCAI) urged cath labs to balance the risk of staff exposure and patient benefit: while primary PCI should be considered the gold standard, fibrinolytics could be considered. A second statement from SCAI recommended that all STEMI patients be brought to the cath lab for primary PCI where possible, but that as COVID-19 wreaks havoc on resources, fibrinolytic therapy might have to be considered.

More of TCTMD's coverage on our COVID-19 hub.
More of TCTMD's coverage on our COVID-19 hub.

Other COVID-19 hot spots have handled things differently. In China, where the epidemic started, experts dealing with COVID-19 recommended fibrinolytic therapy over primary PCI for all STEMI patients. In Italy, by contrast, centers have continued to offer primary PCI where possible, but have restricted it to hub-and-spoke centers, reducing the number of hospitals performing 24/7 PCI from 55 to 13. Gianluca Campo, MD (University of Ferrari, Italy), and colleagues, writing in the European Heart Journal, emphasize the need to be prepared, but point out that primary PCI is still favored in Europe over fibrinolysis.

Dharam Kumbhani, MD (UT Southwestern Medical Center, Dallas, TX), senior author of the Circulation perspective, told TCTMD the paper was an attempt to “lay the groundwork” for when and why hospitals might switch to a lytic-based reperfusion approach. If the interventional workforce is depleted because doctors and other staff have been drafted to work in the ICU, or because of quarantine or illness, it may be simply impossible to provide 24/7 STEMI care in the cath lab. And while the chief concern of physicians deciding on treatment has long been based on risk and benefit, COVID-19 is now forcing physicians to also consider institutional risk as well.

“At my hospital, we have set up a pathway where if we ever got there, we could use lytics,” said Kumbhani. “If we got hit the way New York or New Orleans got hit, we wouldn’t be scrambling to develop [the lytic-based pathway]. Does that mean we’re giving lytics now? No, but we’ve talked about it when things are well. It’s sort of like a will. You do it when you’re well and it’s ready to go.”

Nick Curzen, MD, PhD (University Hospital Southampton NHS, England), president of the British Cardiovascular Intervention Society (BCIS), took issue with the perspective, particularly its tone, saying that even before COVID-19 pandemic, there was never a “blanket” policy of primary PCI for STEMI patients. Business as usual means primary PCI by default, he said, and based on the evidence, hospitals should continue to offer primary PCI as the go-to strategy unless local circumstances dictate that it can’t be delivered.  

“In the UK, our guidance is very carefully worded so that it doesn’t say that everyone should get primary PCI,” Curzen told TCTMD. “What it says is that it should remain the default if it’s possible to deliver. That’s very different thing.”  

In March, BCIS and the British Cardiovascular Society endorsed guidance from the NHS England stating that primary PCI remains the treatment of choice for STEMI. There will be circumstances where that can’t happen, he said, and thrombolysis may need to be considered.

Avoiding the ICU  

James McCabe, MD (University of Washington Medical Center, Seattle), said that “all politics are local,” and that hospitals getting hammered by COVID-19 cases would need to make their own decision about the best treatment approach for STEMI patients.

It’s sort of like a will. You do it when you’re well and it’s ready to go. Dharam Kumbhani

“You have to fit the strategy to the environment,” he told TCTMD. At the moment, McCabe said that even though Seattle was one of the first US cities to experience an outbreak of COVID-19, his center hasn’t been overwhelmed like other area hospitals and they have continued to perform primary PCI for STEMI. “We really haven’t strayed from our primary PCI pathway. Like a lot of centers, we have seen a decrease in the total number of STEMI cases. We discussed it, but ultimately decided against pursuing lytic-based therapy.”

Like everything else, that could change if the situation on the ground changes, he said. 

Pinak Shah, MD (Brigham and Women’s Hospital, Boston, MA), made a similar argument, noting that while they have discussed potentially using fibrinolytic therapy over primary PCI for STEMI cases, they have opted, for the time being, to continue with procedures. Unlike some Boston hospitals, their center also hasn’t been stretched too thin with COVID-19 cases. While there are valid reasons for considering fibrinolytic therapy—avoiding exposure of the cath lab staff to COVID-19-positive patients and concerns about insufficient personal protective equipment (PPE)—Shah said they are worried about patients in whom fibrinolytic therapy might be ineffective. Fibrinolytic therapy fails to achieve reperfusion in roughly one-third of patients, and when these patients are taken to cath lab for emergency reperfusion they might be at higher risk because “they’re in a fully lytic state,” said Shah.

Nonetheless, they “have kept the door open” to the pharmacoinvasive strategy, Shah said. If their hospital is overwhelmed with COVID-19 cases, if there is an increase in the number of STEMI patients coming to the cath lab, if PPE becomes suddenly scarce, or if they lose a number of critical personnel because of quarantine or illness, they will reconsider the lytic-based strategy.

“Fortunately, we haven’t got there yet,” he said. “It’s quite possible that any institution could come to a point where they meet a certain threshold where they need to make that decision that we need to move to a lytic-based strategy.”     

In New York City, where there have been roughly 125,000 confirmed cases of COVID-19, Ajay Kirtane, MD (NewYork-Presbyterian/Columbia University Irving Medical Center, New York, NY), said their center is still performing primary PCI, but they do have a contingency plan in place for lytic-based therapy. That plan would only go into action if there’s a surge that overwhelms their hospital and there is a shortage of PPE.   

Speaking with TCTMD, Habib Samady, MD (Emory University School of Medicine), said they’ve also stuck with primary PCI, noting, like McCabe and Shah, that their STEMI numbers are down since the outbreak began. While the lower STEMI rates factored into their decision, Samady said the administration of fibrinolytics can create burdens elsewhere.  

“The medical resources that are our greatest commodities right now are ventilators and ICU time,” he said. “If you treat someone with fibrinolytics, by definition, they’re more unstable. Not everybody responds, and if they don’t respond, they can re-occlude. These are not patients we can quickly streamline and take care of. They often have to go to the ICU and wait around to see if they re-occlude. If they go for primary angioplasty, you can get in there—of course, you deal with PPE and staff protection—but you could potentially stent an artery and not send them to the ICU but to a floor bed.”

At present, Atlanta hasn’t had an outbreak of COVID-19 cases on par with New York City or other major hot spots, and hospitals are still managing, said Samady. Certainly, if they become overwhelmed, and require a repurposing of cath lab personnel to treat COVID-19 patients, then his institution “might not have the bandwidth to do primary PCI.” Although there has been a COVID-19 surge, they currently have had the cath infrastructure, personnel, and PPE to safely perform primary PCI in STEMI cases, said Samady.

Circumstances Unique to Every City and Hospital

To TCTMD, McCabe agreed that there certainly are circumstances where fibrinolytic therapy makes the most sense for treating patients. Like others, he said the lytic-based strategy often means only deferring, rather than avoiding, the trip to the cath lab. In some scenarios, that deferral can be helpful, though, especially if point-of-care testing for COVID-19 becomes more widely available. Fibrinolytic therapy would buy physicians some time while waiting for the results of the COVID-19 test, and if the test were negative, McCabe said, then the cath lab staff wouldn’t need to go through the same “mishegas,” Yiddish for craziness, as they would when stenting a COVID-19-positive patient, he said.

At the moment, though, McCabe said they are sticking with primary PCI because they still have available resources and sufficient staffing to continue to do so with appropriate precautions. Another reason, said McCabe, is that there were concerns, based largely on anecdotal evidence, of STEMI-like ECG patterns in COVID-19-positive patients, possibly related to myocarditis. “Those seem like patients we really didn’t want to give lytics to because they obviously don’t have a thrombotic culprit lesion,” he said.

Samady also noted that patients sick with COVID-19 will present with abnormal ST-segment changes unrelated to classic plaque rupture, but possibly related to in situ thrombosis, inflammation, or spasm. In the cath lab, physicians can tease out the reason for those abnormal ECG findings, he said.

Kirtane pointed to a new case series from six New York City hospitals published Friday in the New England Journal of Medicine that identified 18 patients with COVID-19 who had ST-segment elevation indicating acute MI. There was a fair amount of variability in presentation: some patients presented with ST-segment elevation, others developed that in hospital, and a high prevalence had nonobstructive disease. The case report, said Kirtane, reiterates concerns about fibrinolysis “because you’re giving a drug that has a high rate of complications to a pathophysiology that isn’t an acute thrombotic occlusion.”   

Kumbhani acknowledged that physicians are concerned about the STEMI-like mimics in COVID-19 patients, but right now the evidence is largely based on case reports. There is currently no denominator, he said, meaning they have no idea what percentage of STEMI cases presenting to the hospital trigger a false activation of the cath lab because of COVID-19.

I don’t think most centers in the US are using enough lytic therapy to completely feel comfortable with the decision. Pinak Shah

Additionally, while primary PCI has been shown to be superior to fibrinolytic therapy and is the gold standard for STEMI care, Kumbhani said the current pandemic has thrown everything out of whack. Timely primary PCI relies on systems of care, but those systems are stressed when a COVID-19 patient presents with STEMI. For one, door-to-balloon time “goes out the window” given the necessary protocols in place to prevent transmission and ensure staff safety. Even in COVID-19-negative patients, there are delays because field activation of the lab has been discontinued and all patients must present to the ER. There is also time needed to establish contact history, symptoms, chest X-rays, and so on, before they can be shipped to the cath lab.  

“The superiority of primary PCI over lytics is contingent upon us meeting that 90-minute door-to-balloon time,” said Kumbhani. “If you’re getting into delays of hours before reperfusion, even though you’ve done the primary PCI, I’m not sure if that would have been as good [compared] with giving lytics early.”

There is even contemporary evidence to show that when delays are inevitable, fibrinolysis is a good alternative to primary PCI. The STREAM trial, which was published in 2013, showed that prehospital fibrinolysis with timely coronary angiography was as effective as primary PCI in STEMI patients who presented early but were unable to be revascularized within 1 hour of medical contact. Intracranial hemorrhage was 1% with fibrinolysis versus 0.5% with PCI. A little more than one-third of patients did require emergency angiography, however.

In geographically isolated areas, as well as developing countries, fibrinolytic-based reperfusion is still the go-to strategy, said Kumbhani.

To TCTMD, Curzen emphasized the superiority of primary PCI for STEMI, highlighting its better outcomes, lower complication rates, and shorter hospital stay.

“There is no question that fibrinolysis for STEMI is better than no treatment, but that doesn’t mean you can justify choosing it for a patient who could have had a better treatment, which is primary angioplasty,” he said. Like others, he noted that failed reperfusion with fibrinolytic therapy is a significant issue, and that these patients are then referred for rescue PCI. “Do you really want between one-quarter to one-third of patients who are COVID-19-positive to need a much higher-risk angioplasty than the one they could have had an hour or two before?”

For patients who are healthy enough to go to the cath lab, but who are treated successfully with fibrinolysis instead, Curzen noted the guidelines still recommend an angiogram within 24 hours of reperfusion. “What you’re doing by fibrinolytic therapy over primary PCI in a patient who could have both—and that’s the key, the patient could have both—is potentially creating a significant subgroup who need an angiogram anyway,” he explained.

While fibrinolysis may limit exposure to the cath lab personnel, the shorter hospital stay with primary PCI limits exposure to the overall hospital staff. Moreover, the need for rescue PCI in nearly a third of patients, as well as the subgroup of patients requiring the follow-up angiogram, creates even greater exposure than a strategy of primary PCI first in eligible patients, said Curzen.     

What Happens If It Happens?      

To TCTMD, Shah said identifying who is an appropriate candidate for fibrinolysis can be a challenge, especially since it’s been a while since physicians have had to consider this treatment option for STEMI.

“There are certain patients where you know you won’t even try—maybe they’re in cardiogenic shock and urgent and definitive revascularization is going to be important, or the extremely elderly, or very small patients who might be at risk for intracranial hemorrhage,” Shah said. “A lot of these concerns we have for lytics, we don’t give as much thought when we think about taking our patients to the cath lab. I don’t think most centers in the US are using enough lytic therapy to completely feel comfortable with the decision. I can imagine most emergency room doctors and many cardiologists aren’t comfortable with the decision.”

Of the fibrinolytics, tenecteplase (TNKase; Genentech) is a rapid-onset, single-bolus, plasminogen activator that is easy to deliver, said Samady. Alteplase (Activase; Genentech), which is infused over 60 to 90 minutes, is a little more complicated, and physicians might not be as familiar with its use, he said.

When the COVID-19 pandemic eases, or when a vaccine is developed, Shah said he doesn’t believe this era will have a lasting impact on treatments for patients with STEMI. Primary PCI, given the strength of evidence, will likely bounce back. “Of all the things we do in interventional cardiology, particularly in coronary interventions, the one therapy we can all agree on that is beneficial to patients is primary PCI,” he said. “There’s a lot of debate about some of the other things we do in coronary interventions, but primary PCI is something we all truly believe in. I think it’s an area that will get back to business as usual once we get beyond the current situation.”   

Michael O’Riordan is the Managing Editor for TCTMD. He completed his undergraduate degrees at Queen’s University in Kingston, ON, and…

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  • Daniels and Kumbhani report no relevant conflicts of interest.