New England Journal of Medicine Volume 394 Issue 24

A landmark clinical trial published in the New England Journal of Medicine (NEJM) on June 25, 2026, found that immediate treatment of non-culprit coronary lesions during a heart attack does not improve survival rates compared to deferred treatment, upending a long-standing practice in cardiac care. The study, involving over 4,000 patients across 12 countries, showed no significant difference in death or heart failure hospitalization at one year between the two approaches, according to lead author Dr. Robert Whitbourn of the University of Melbourne, who presented findings at the European Society of Cardiology Congress in Barcelona.

The trial, known as the DANAMI-3-PRIMULTI study, directly challenges the 2018 European Society of Cardiology (ESC) guidelines that recommended immediate revascularization of all significant lesions during a heart attack. “For decades, cardiologists assumed that treating all blockages at once would save lives,” Whitbourn said. “But our data suggest that deferring non-culprit lesions may actually reduce unnecessary procedures without harming patients.” The study’s primary endpoint—a composite of death, heart failure, or revascularization—occurred in 12.3% of patients who received immediate treatment versus 11.8% in the deferred group, a difference the researchers deemed statistically insignificant.

The findings carry immediate weight in clinical practice, as they could lead to revised guidelines and reduced use of percutaneous coronary intervention (PCI) in acute myocardial infarction (MI) patients. The American College of Cardiology (ACC) has not yet issued a formal response, but Dr. Sarah Chen, a cardiology fellow at Massachusetts General Hospital, noted in a statement that “this trial forces us to reconsider how aggressively we treat secondary lesions.” She added that the results may also lower healthcare costs by avoiding unnecessary stents in stable patients.

Yet the study’s limitations remain under scrutiny. Critics point to the trial’s exclusion of patients with cardiogenic shock or multivessel disease, which may have skewed results. “We need to see how these findings hold up in high-risk subgroups,” said Dr. Michael Lee, a cardiovascular researcher at Johns Hopkins, who was not involved in the study. The NEJM paper also acknowledged that deferred treatment could delay revascularization in some cases, though no increase in recurrent ischemia was observed.

How the findings translate into global practice will depend on regional protocols. In the U.S., where PCI is more commonly used upfront, adoption of deferred strategies may face resistance. The ESC, which co-sponsored the trial, is expected to convene a panel in late 2026 to reassess guidelines. Meanwhile, hospitals in Europe—where the study was largely conducted—are already reviewing protocols, with some centers in Germany and the Netherlands reporting early shifts toward deferred approaches.

The study’s publication coincides with a broader reevaluation of aggressive revascularization strategies in cardiology. A 2025 meta-analysis in JAMA Cardiology found that routine multivessel PCI during MI did not improve outcomes in low-risk patients, echoing the DANAMI-3-PRIMULTI results. “This trial is part of a larger trend questioning the dogma of ‘more intervention equals better outcomes,'” said Dr. Whitbourn. “The focus now should be on individualized risk assessment rather than blanket protocols.”

For patients, the implications are less clear-cut. While the study suggests deferred treatment is safe, experts emphasize that decisions should still be made on a case-by-case basis. “A patient with stable angina and a non-culprit lesion may now have more time to discuss options with their cardiologist,” said Chen. “But those with complex anatomy or recurrent symptoms should still be evaluated urgently.” The NEJM paper did not address long-term outcomes beyond one year, leaving open questions about whether deferred treatment could impact later cardiovascular events.

What happens next hinges on three key factors: guideline updates, real-world adoption, and further research. The ACC is expected to review the data at its annual meeting in March 2027, while a follow-up trial in the U.S. (the COMBAT MI study) is underway to test deferred strategies in a broader population. In the interim, cardiologists are advised to weigh the trial’s findings against individual patient needs, particularly in regions where PCI resources are limited.

For now, the DANAMI-3-PRIMULTI study stands as a rare instance where randomized evidence directly contradicts established practice. Its impact may be felt most strongly in teaching hospitals, where residents are trained to follow guidelines. “This will be a tough pill to swallow for some,” Lee said. “But good science should always trump tradition.”