Complete Revascularization in STEMI: What Trials and Experience Have Taught Me

Jaya Mallidi, MD, MHS


September 22, 2021

Current evidence favors complete revascularization because it reduces the risk for repeat revascularizations and nonfatal MI, but there are practical and clinical considerations. You'll have to wait until I review the evidence before I reveal what we did in this case.

Complete vs Culprit Lesion–Only Revascularization: Evidence to Date

Several randomized trials among patients with STEMI and multivessel disease have compared complete revascularization, which includes the nonculprit lesion in addition to the infarct-related artery, with culprit lesion–only PCI (Table). Both groups were treated with appropriate guideline-directed medical therapy. All of these trials were in hemodynamically stable patients without cardiogenic shock. In these studies, complete revascularization was associated with a reduced risk for major cardiovascular events, mainly driven by reductions in repeat revascularizations and nonfatal myocardial infarction. In STEMI patients with multivessel disease and cardiogenic shock, immediate multivessel PCI compared with PCI on only the culprit vessel was associated with increased 30-day risk for death and severe renal failure leading to renal replacement therapy.

Complete revascularization in hemodynamically stable STEMI patients with multivessel disease is a class IIb recommendation in the current US guidelines and class IIa in European guidelines. But these guidelines have not been updated since the publication of the COMPLETE trial.

The largest study to date, COMPLETE compared a strategy of staged PCI of all suitable nonculprit lesions in addition to the culprit vessel or culprit-only PCI in more than 4000 patients with STEMI and multivessel disease. Complete revascularization was performed regardless of presence or absence of clinical symptoms or ischemia, and the median time from randomization to nonculprit PCI was 1 day for those who underwent PCI during the index hospitalization and 23 days for those who underwent PCI later. At 3-year follow-up, the composite outcome of cardiovascular death or new myocardial infarction was lower in the completely revascularized group (Table). This result was driven by a lower incidence of nonfatal MI. There was no statistical difference between the two groups in the rate of cardiovascular death (2.9% vs 3.2%; hazard ratio, 0.93; 95% CI, 0.65-1.32).

Table. Randomized Controlled Trials Comparing Complete Revascularization With Culprit Lesion–Only PCI in Patients With STEMI

of Publication)
Definition of
Timing of Nonculprit
Lesion Intervention
Follow-up (mo)
Complete vs Culprit
465 ≥ 50% No Index procedure 23 Death, MI,
refractory angina
9% vs 23%
P < .01
296 > 70% single view or
> 50% two views
No Index procedure or
12 All-cause death,
MI, heart failure,
ischemia-driven TLR
10% vs 21.2%
P = .009

627 ≥ 50% Yes Index procedure or
27 All-cause death,
MI, and
13% vs 22%
P = .004
885 ≥ 50% Yes Index procedure or
12 All-cause death,
MI, revascularization,
7.8% vs 20.5%
P < .001


4041 ≥ 70% or
50%-69% +
FFR ≤ 0.80
Yes Index
discharge within
45 days
36 Cardiovascular
death and MI
7.8% vs 10.5%
P = .004
FFR = fractional flow reserve; MI = myocardial infarction; STEMI = ST-segment elevation myocardial infarction; TLR = target lesion revascularization

Heterogeneity of Studies

Although all studies favor complete revascularization, from a practical standpoint there is significant variation in clinical practice, which reflects the heterogeneity in these randomized studies. Specifically:

  • The timing of intervention: Complete revascularization could be done during the index procedure or index hospitalization, or as a staged intervention postdischarge. There are no randomized controlled trials comparing these various timepoints. In COMPLETE, nonculprit revascularization was performed during index hospitalization or after discharge within 45 days. The benefit of complete revascularization was observed independent of the timing of intervention.

  • Evaluation of the nonculprit lesion: Some trials used angiography alone, whereas others used fractional flow reserve or a combination of techniques to guide intervention. Even when angiography alone was used, the threshold for significant disease was defined differently (Table). In COMPLETE, significant nonculprit disease was defined as angiographic stenosis ≥ 70%, or angiographic disease 50%-69% with fractional flow reserve ≤ 0.80. Less than 1% of patients had nonculprit lesions meeting the latter criteria.

Assessment of Nonculprit Lesions Is Difficult in STEMI

Angiography alone is not a good predictor of the functional significance of a lesion, even in stable patients. This is especially true for eccentric and intermediate-range lesions. In acute STEMI, with associated spasm of the vessels, using angiography alone could result in overestimation of nonculprit lesion severity.

After STEMI, transient changes in microvasculature may occur that affect hyperemic indices commonly used to assess the physiologic significance of a lesion in both infarct and noninfarct areas, which could make fractional flow reserve (FFR) less accurate. FFR is the ratio of hyperemic distal coronary pressure to aortic pressure. In a recent study, the FFR value of a nonculprit lesion was significantly augmented at the index procedure compared with FFR measured at 30 days' follow-up. This suggests that the severity of nonculprit lesions may be underestimated using FFR in the acute setting, especially in the case of large infarctions.

A recent multicenter randomized trial, FLOWER-MI compared FFR-guided and angiography-guided complete revascularization in more than 1100 patients with STEMI and multivessel disease. Full revascularization, including FFR measurement, was done at the time of the index procedure or before discharge (within 5 days). Nonculprit disease was defined as lesions ≥ 50% in an epicardial vessel ≥ 2.0 cm. There was no statistically significant difference in the composite endpoint of death, MI, or urgent revascularization at 1 year between the two strategies, but the study was underpowered because of a lower-than-expected event rate. After 6 months, there was a trend toward higher event rates with the FFR-guided strategy. It's feasible that FFR underestimated the severity of the nonculprit lesions in the acute setting and significant lesions were left untreated and worsened during follow-up, requiring urgent revascularization.

Other Ways to Assess Lesion Severity

Given the limitations of angiography and FFR, what other tools might we use to assess nonculprit lesions? The instantaneous wave-free ratio (iFR) is a resting diastolic index used to measure the physiologic significance of a lesion. It has been shown to be valid for excluding nonculprit lesions in the setting of acute STEMI, but it may overestimate their severity. Its use in guiding complete revascularization in STEMI is currently under investigation in the iMODERN trial.

According to a State of the Art review in JACC, noninvasive modalities, such as stress echocardiography, myocardial perfusion scintigraphy, cardiac magnetic resonance, or single-photon emission tomography, to assess nonculprit lesion significance may be considered depending on local practice patterns and availability. However, there is limited evidence supporting the use of these modalities for clinical decision-making regarding revascularization of the nonculprit lesion. In in my experience, in post-MI patients, interpretation of ischemia noninvasively in the territory of noninfarct-related artery is challenging, given the preexisting wall-motion abnormalities and perfusion defects from recent MI.

Practical Issues Regarding Nonculprit Lesion Intervention During Index Admission

We do not know with certainty the best mode or timing to accurately assess the physiologic significance of a nonculprit lesion in the setting of STEMI. In patients with STEMI who are not in cardiogenic shock, I consider the following factors when planning a nonculprit intervention during the index procedure or admission:

  • Anatomy of the lesion: Complex anatomical lesions involving ostia, bifurcations, severe calcification, or diffusely diseased and tortuous vessels require planning and time. These complex interventions may not be tolerated in the acute setting, especially if the index infarct is large. In COMPLETE, the average syntax score of the nonculprit lesions was low, at 4.8, and the overall baseline syntax score was also low, at 16. This suggests that its more favorable to intervene during index admission, when anatomical complexity is low.

  • Baseline renal function: In patients with compromised baseline renal function, it's best to avoid an additional intervention during index admission to avoid worsening of the renal function. Only a small percentage of patients in COMPLETE (2%) had significantly impaired renal function at baseline.

  • Comorbidities and assessment of medication compliance: Given the acuity of the situation in STEMI, there may not have been time for a full assessment of the patient's comorbidities, preferences, or ability to adhere to dual antiplatelet therapy. Staging the nonculprit intervention, will provide time for a comprehensive assessment of the patient.

What Did We Do With Our Patient?

Our 72-year-old patient presented in the clinical vignette meets the enrollment criteria for both the COMPLETE and the FLOWER-MI trials. So, the findings from these studies are relevant to his case. Given his renal dysfunction, and the complex anatomy of the RCA lesion, a second procedure during his index hospitalization is potentially harmful. The third option — performing revascularization only if the patient is symptomatic or stress test — shows ischemia is not supported by the findings from COMPLETE. Also, accurate interpretation of inferior ischemia in the setting of a recent anterior infarct on a noninvasive modality is challenging. We went with the last option and brought the patient back 4 weeks later. We performed FFR of the RCA lesion; it was 0.85, and revascularization was not done. The patient quit smoking, and goal-directed medical therapy was continued to control his risk factors.

Although randomized trials support complete revascularization for STEMI patients with multivessel disease, the mode of assessment and timing of intervention of a nonculprit lesion is not yet definitively established. There are practical and clinical challenges to doing this during the index procedure. On the basis of current evidence, I drew up an algorithm for how I approach these cases (Figure).

Figure. Algorithm for management of nonculprit lesions in STEMI.

Jaya Mallidi, MD, MHS, trained in and practiced interventional cardiology for 5 years and now works as a general cardiologist. An ardent patient advocate, she writes opinion pieces using patient stories as context to highlight problems in the practice of modern-day medicine. In addition, she enjoys sketching and playing tennis.

Follow Jaya Mallidi on Twitter

Follow | Medscape Cardiology on Twitter

Follow Medscape on Facebook, Twitter, Instagram, and YouTube


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: