Immediate or deferred non-culprit lesion pci in myocardial infarction: refining the timing of completeness

Over the past decade, the management of non-culprit coronary lesions (NCLs) in patients with acute myocardial infarction (MI) and multivessel coronary artery disease (MVD) has evolved substantially. The paradigm of restricting percutaneous coronary intervention (PCI) to the culprit lesion, during the initial procedure, has evolved into a complete revascularization strategy. Randomized trials and meta-analyses have consistently demonstrated that treating significant NCLs reduces recurrent ischemic events, new hospitalizations, and the need for urgent revascularization (1,2). Yet, despite this broad consensus, two critical practical questions remain unresolved: how should a non-culprit lesion be assessed to determine its suitability for stenting, and when should non-culprit lesions be treated? Some studies have investigated the role of physiological assessment, with conflicting results (3,4). Moreover, the optimal timing of revascularization (immediate vs. staged) has not yet been investigated in adequately powered randomized superiority trials. Currently, there is no clear recommendation for routinely use of physiology, nor is there a recommendation for immediate vs. staged PCI (i.e., during index hospitalization or within 45 days of discharge) (2,5-8). European guidelines allow for the revascularization of all lesions during the index PCI. The decision should be made based on the anatomical complexity (9). Immediate non-culprit PCI offers theoretical advantages, including a single procedure, reduced hospitalization, avoidance of repeat vascular access, and earlier ischemic risk reduction. Conversely, deferred PCI allows for hemodynamic stabilization, recovery from acute inflammation, more reliable physiological assessment, and improved lesion characterization.

In October 2025 Nijveldt and colleagues presented data from the iMODERN trial by comparing immediate non-culprit-lesion percutaneous coronary intervention (PCI) guided by instantaneous wave-free ratio (iFR), with deferred PCI guided by stress cardiac magnetic resonance imaging (MRI) in patients with ST-segment elevation myocardial infarction (STEMI) and multivessel disease (10). This trial moves beyond the binary question of whether to focus on non-culprit lesions, paying attention to the type of test used for lesion assessment and the timing of revascularization. Patients in the iFR group underwent physiological assessment at the time of primary PCI for all non-culprit lesions with more than 50% stenosis. Patients in the MRI group received an MRI assessment at a median of 27 days (interquartile range 15–37 days) after the initial procedure. Among positive lesions, PCI was performed at a median of 40 days (interquartile range 28–58 days).

The main finding—that immediate non-culprit PCI does not offer clear clinical advantages over a deferred approach—will likely resonate with many clinicians who have suspected as much based on their experience. Complete revascularization during the initial procedure may be reasonable in the NSTEMI setting due to the ambiguity of the culprit lesion. However, it may be less useful in the STEMI setting. The absence of a difference in the primary endpoint suggests that once the culprit artery is treated, the NCL assessment can be safely delayed and performed with non-invasive evaluation. Recent studies comparing immediate vs. deferred complete PCI strategy are summarized in Table 1. These findings support a flexible approach to clinical practice rather than a dogmatic one.

Otherwise, there are some issues that must be considered. First, patients in the MRI group with a positive ischemia lesion received PCI a median of 40 days after the initial procedure. This aligns with the COMPLETE trial design, in which PCI of NCLs was performed within 45 days. Second, over the past ten years, cardiologists have progressively abandoned stress testing after PCI, primarily due to the availability of immediate tools capable of classifying lesions in a single session, and stress perfusion MRI is not widely available, raising some doubts about its cost-effectiveness. Third, the trial's results are only hypothesis-generating, primarily because the primary EP rate was much lower than expected (9.8% vs. 16%), despite the prolongation of follow up. This makes the study underpowered to detect any difference between the two groups. Fourth, individuals with hemodynamic compromise, complex lesions with a high SYNTAX score, or severe comorbidities were underrepresented, which limits the study's generalizability to these higher-risk groups; further studies are needed for those subgroups.

Despite these limitations, the study confirms that deferring a non-culprit lesion for up to 40 days is reasonable. However, it would be simplistic to interpret the results as evidence that timing never matters. The trial population is a select group of patients deemed suitable for either strategy, so the findings may not apply to individuals with ongoing ischemia, cardiogenic shock, or complex coronary anatomy.

One of the enduring controversies in non-culprit PCI concerns the reliability of physiological measurements, such as the fractional flow reserve (FFR) during the acute phase of myocardial infarction (MI). Microvascular dysfunction, oedema, and neurohumoral activation can influence coronary flow and pressure gradients, which can lead to the misclassification of lesion severity. Otherwise, robust evidence supports the use of FFR in MI setting; un update metanalysis showed that a complete functional-guided revascularization resulted in lower incidence of cardiovascular death compared to an angio-guided approach (11). Adenosine-free indices, such as iFR, may mitigate unresponsiveness to adenosine and could be more reliable in the setting of acute myocardial infarction. The trial by Nijveldt et al., which incorporates physiological guidance into both immediate and deferred strategies, implicitly tests the clinical relevance of these concerns. The lack of a clear advantage for deferred PCI suggests that physiological assessment during the initial hospitalization may be sufficiently robust to guide safe and effective revascularization. Nonetheless, this conclusion should be tempered by the recognition that physiology is one component of decision-making that complements angiographic appearance, plaque morphology, and clinical presentation. The evaluation and management of vulnerable plaques represent a future challenge in the field of interventional cardiology (12). Combining timing strategies (immediate vs deferred) with imaging-based plaque characterization could enable a more personalized approach, targeting both ischemia and vulnerability. Ongoing studies, integrating intracoronary imaging or non-invasive functional testing, may further refine this approach (COMPLETE2 trial-NCT05701358).

In conclusion, Nijveldt et al. took an important step toward building the body of evidence on STEMI and MVD. They demonstrated that immediate and deferred NCL-PCI have comparable clinical outcomes in selected patients. This shifts the focus from rigid timing mandates to patient-centered decision-making. For clinicians, this is a reassuring message: the most relevant message is that routine immediate PCI of non-culprit lesions should not be mandated in all STEMI patients with multivessel disease; instead, guidelines should more explicitly support a flexible strategy, allowing deferred revascularization when clinically appropriate. In an era increasingly defined by precision medicine, the question is no longer simply whether to treat non-culprit lesions but also how and when to do so in the best interest of each patient.

Acknowledgments

None.

Footnote

Provenance and Peer Review: This article was commissioned by the editorial office, AME Clinical Trials Review. The article has undergone external peer review.

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