How and When: Complete Revascularization for Acute Coronary Syndromes

THE EVOLUTION OF EVIDENCE

Early United Kingdom-based trials such as preventive angioplasty in acute myocardial infarction (PRAMI)^[3] and complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for stemi and multivessel disease (CvLPRIT)^[4] challenged the dogma, demonstrating that treating non-culprit lesions during the index admission, and often the index procedure, reduced major adverse cardiovascular events. These studies, though modest in size, set the stage for larger, more definitive trials. Third danish study of optimal acute treatment of patients with stemi: primary pci in multivessel disease (DANAMI-3 PRIMULTI)^[5] and comparison between FFR guided revascularization versus conventional strategy in acute stemi patients with MVD (COMPARE-ACUTE)^[6] introduced physiology-guided approaches, using fractional flow reserve (FFR). These studies further demonstrated the benefit of complete revascularization, primarily through reductions in urgent repeat procedures, but lacking reductions in hard endpoints.

The landmark complete versus culprit-only revascularization strategies to treat multivessel disease after early PCI for stemi (COMPLETE) trial^[7] provided the clearest answer yet: Complete revascularization significantly reduced cardiovascular death and myocardial infarction compared to culprit-only percutaneous coronary intervention (PCI). This pivotal trial led to a Class I, Level A recommendation in both American and European guidelines, a rare distinction in STEMI management.

Most recently, the DANAMI-3 PRIMULTI 10-year follow-up confirmed the sustained durability of the benefit of complete revascularization over culprit-only PCI for ACS patients.^[8]

TIMING AND STRATEGY: IMMEDIATE VERSUS STAGED

Recent studies have focused on the timing of revascularization. The percutaneous complete revascularization strategies using sirolimus-eluting biodegradable polymer-coated stents in patients presenting with acute coronary syndromes and mutivessel disease (BIOVASC)^[9] and multi-vessel immediate vs staged revascularization in acute myocardial infarction (MULTISTARS AMI)^[10] trials compared immediate versus staged complete revascularization in stable ACS patients. Both approaches were found to be safe, with immediate revascularization showing non-inferiority and, in some cases, a trend toward better outcomes. The optimal timing of fractional flow reserve-guided complete revascularization for non-infarct-related artery in ST-segment elevation myocardial infarction with multivessel disease (OPTION-STEMI) trial^[11] added nuance, suggesting that immediate PCI may not be non-inferior in all subgroups, particularly those with heart failure features.

Network meta-analyses involving thousands of patients have confirmed that multivessel PCI within the index hospitalization – whether immediate or staged – represents the safest and most efficacious approach for stable STEMI patients.^[12]

PHYSIOLOGY VERSUS ANGIOGRAPHY GUIDANCE

The debate over physiology-guided versus angiography-guided PCI remains unresolved. Trials such as flow evaluation to guide revascularization in multivessel ST-elevation myocardial infarction (FLOWER-MI)^[13] and fractional flow reserve vs angiography-guided strategy for management of non-infarction related artery stenosis in patients with acute myocardial infarction (FRAME-AMI)^[14] have produced mixed results, with FRAME-AMI hinting at a long-term advantage for FFR guidance, while FLOWER-MI found no clear difference. The main advantage of physiology-guided PCI is a reduction in the number of interventionss. The ongoing COMPLETE-2 trial (enrolling over 5000 patients and assessing both timing and physiology-guided strategies) is expected to provide further clarity on the utility and safety of physiology guidance in this setting.

SPECIAL POPULATIONS: NON-STEMI, CARDIOGENIC SHOCK, AND OLDER PATIENTS

For non-st segment elevation myocardial infarction (NSTEMI), the evidence base is less robust, relying mainly on data derived from observational studies. While some data suggest better outcomes with complete revascularization, others highlight increased in-hospital complications, reflecting the heterogeneity of this patient group.^[15]

In patients with cardiogenic shock, the culprit lesion only PCI versus multivessel PCI in cardiogenic shock (CULPRIT-SHOCK) trial demonstrated a clear benefit for culprit-only PCI, with a significant reduction in death or severe renal failure compared to immediate multivessel PCI. Thus, guidelines recommend a more conservative approach in this subgroup.^[16]

Older patients present unique challenges, but recent studies indicate that complete revascularization can be beneficial, provided the patient’s overall condition and comorbidities are carefully considered^[17]

CURRENT GUIDELINES AND TAKE-HOME MESSAGES

The current european society of cardiology (ESC) guidelines^[2] recommend complete revascularization during the index procedure, index admission, or within 45 days for stable STEMI patients, using angiographic severity rather than physiological testing during the acute phase. For NSTEMI, the approach should be individualized, balancing the potential benefits against patient tolerance and risk.

CONCLUSION

• Complete revascularization is strongly supported by randomized controlled trial (RCT) evidence in STEMI, reducing hard endpoints like cardiovascular death and myocardial infarction (MI)

• For NSTEMI, benefits are seen mainly from observational data, with ongoing trials expected to clarify the optimal strategy

• Timing – immediate versus staged – appears flexible for most stable patients, with safety and efficacy maintained. Perhaps the best compromise is staged procedures completed within the index hospital admission

• Physiological guidance may reduce unnecessary interventions, but its role in acute coronary syndrome (ACS) remains to be fully defined

• Special populations require tailored approaches, with culprit-only PCI favored in cardiogenic shock.

As the field continues to evolve, ongoing research and technological advances – including AI-driven plaque assessment – promise to further refine our approach to complete revascularization in ACS.