Transfer for Primary PCI Still Better Than Fibrinolysis After 16 Years: DANAMI-2

PARIS, France—Sending patients with STEMI to invasive centers for primary PCI rather than keeping them and administering fibrinolytics has had long-lasting clinical benefits, extended follow-up of the randomized DANAMI-2 trial shows.

“We found that the benefit of primary PCI over fibrinolysis was sustained after 16 years,” according to Pernille Thrane, a medical student at Aarhus University Hospital, Denmark, who reported that patients transferred for an intervention had lower risks of death/reinfarction, reinfarction, and cardiac death.

This is the first time primary PCI has been shown to reduce the long-term risk of cardiac death, she said during her presentation here at the European Society of Cardiology Congress 2019. The findings were published simultaneously online in the European Heart Journal.

Speaking at a press conference, senior investigator Michael Maeng, MD, PhD (Aarhus University Hospital), said “physicians should feel confident that primary PCI remains the best way to treat STEMI patients, even after 16 years of follow-up, if transport can be achieved within 2 hours.”

Fibrinolysis was the go-to strategy for reperfusion in patients with STEMI until trials published in the 1990s demonstrated the superiority of primary PCI when patients were admitted to an invasive center.

DANAMI-2 was the first—and still the largest—trial pitting fibrinolysis against primary PCI in which transfer from a referral hospital to an invasive center was part of the protocol, Maeng said. It included 1,572 patients with STEMI (median age 63 years; about three-quarters men); those who presented to invasive centers were randomized to primary PCI or fibrinolysis and those who presented to other hospitals were randomized to transfer for an intervention or fibrinolysis.

Published in 2003, the main results showed that patients who were sent for primary PCI had a lower risk of death, reinfarction, or disabling stroke at 30 days. Those benefits were sustained at 3-year follow-up.

The investigators conducted follow-up through 16 years using Danish national registries, and found that transfer for primary PCI was associated with:

• A 3.6% absolute reduction in the composite of death or reinfarction (58.7% vs 62.3%; HR 0.86; 95% CI 0.76-0.98).
• A 5.5% absolute reduction in reinfarction (19.0% vs 24.5%; HR 0.75; 95% CI 0.60-0.93).
• A 4.4% absolute reduction in cardiac death (18.3% vs 22.7%; HR 0.78; 95% CI 0.63-0.98).

Compared with fibrinolysis, primary PCI extended the time to a first composite event or reinfarction by about 1 year on average.

There was no difference in all-cause death at 16 years (50.5% with primary PCI and 51.3% with fibrinolysis), although there would have been an advantage for PCI if the follow-up had stopped at 10 years, Maeng said.

The study “supports the current international guidelines which state that primary PCI should be offered if time of STEMI diagnosis or first medical contact to reperfusion (wire crossing) is within 120 min, and reinforce that a  primary PCI strategy with fast access to primary PCI-capable hospitals should be implemented in countries or regions where this strategy is possible,” the authors write in their paper.

No Direct Impact on Practice in 2019

Serving as a discussant after Thrane’s presentation, Borja Ibáñez, MD, PhD (Spanish National Center for Cardiovascular Research and Fundación Jimenez Diaz University Hospital, Madrid, Spain), said “this is the first time that this strategy of transfer to PCI has [been] shown to be associated with a significant reduction in a very hard endpoint, in [this] case, cardiac mortality.” The main drivers of the difference, he suggested, are probably the reduction in rehospitalizations for MI, which was already seen at 30 days, and lower rates of mechanical revascularization.

But both Thrane and Ibáñez pointed out that management of STEMI patients has changed dramatically since DANAMI-2 started two decades ago. Ibáñez said modifications have been made to antithrombotic regimens and the use of rescue PCI and angiography in patients undergoing fibrinolysis. Today, it is known that fibrinolysis is a pharmacoinvasive strategy, he said, and that every patient receiving fibrinolytic therapy should have angiography performed 2 to 24 hours later and then have all severe stenoses revascularized. “These differences in the management of patients undergoing fibrinolysis probably explain to some extent, most of the differences [in outcomes],” he said.

Ibáñez concluded: “Compared to transfer to PCI, immediate stand-alone fibrinolysis—and I’m highlighting stand-alone fibrinolysis, which means fibrinolysis without angiography—is associated with higher long-term cardiac mortality. Most probably these data do not have a direct clinical impact on [practice in] 2019, but this is strong reinforcement that the pharmacoinvasive strategy is the clearly recommended protocol for patients undergoing fibrinolysis.”

Improving STEMI Care Worldwide

Commenting for TCTMD, C. Michael Valentine, MD (Centra Medical Group Stroobants Cardiovascular Center, Lynchburg, VA), immediate past president of the American College of Cardiology, said the finding of an advantage for primary PCI is not surprising. “I think it is just one more confirmation that the results are maintained long-term, and I think what it does is it compels us to continue the work on building STEMI systems of care,” Valentine said.

“Institutions and health systems and communities have to maintain STEMI systems of care for all patients so that they get the most appropriate and quickest therapy,” he continued. “And that means that if PCI is not available within 2 hours, fibrinolysis is helpful and has a long-lasting impact. But if you look at what saves more lives, more cardiovascular lives, and reinfarction, it’s PCI.”

In the United States, there remain challenges in the development of STEMI systems of care, especially in rural areas, where patients still sometimes are not appropriately transferred from non-PCI hospitals to PCI-capable centers, he said. There are also continuing “turf battles” between hospitals when it comes to deciding whether to bypass non-PCI hospitals to take STEMI patients directly to invasive centers. Overall, however, “I think we’re doing a good job in the United States,” Valentine said, adding that education and state STEMI initiatives have been able to overcome some of those issues.

But there’s still work to be done globally, he said. “The availability of PCI, even the availability of thrombolytics, worldwide is still  a major issue,” Valentine said. “If you take low- and middle-income countries and you go outside of the major metropolitan areas, there are patients that don’t get treated for heart attacks for many hours, so the mortality rates are dramatically higher.”

He said the United States should play a big role in helping to address those problems: “I think the United States has been a leader in systems of care, and I think we’ve got to continue that. I think we just need to be able to educate and work with systems worldwide so that we can improve care.”