New England Journal of Medicine SEPTEMBER 01, 2019

Complete Versus Culprit-Only Revascularization to Treat Multivessel Disease After Early PCI for STEMI (COMPLETE)

Mehta SR, Wood DA, Storey RF, et al.

Bottom Line

The COMPLETE trial demonstrated that in patients with STEMI and multivessel coronary artery disease, a strategy of staged complete revascularization significantly reduces the risk of cardiovascular death or myocardial infarction compared to a culprit-lesion-only approach.

Key Findings

1. Complete revascularization significantly reduced the first coprimary outcome (cardiovascular death or myocardial infarction) with a hazard ratio of 0.74 (95% CI, 0.60 to 0.91; P=0.004) at a median follow-up of 3 years.
2. The second coprimary outcome (cardiovascular death, myocardial infarction, or ischemia-driven revascularization) was also reduced with a hazard ratio of 0.51 (95% CI, 0.43 to 0.61; P<0.001).
3. There was no significant difference between the two groups regarding major bleeding, stroke, or stent thrombosis.
4. The benefit of complete revascularization was consistent regardless of the timing of the staged procedure (during index hospitalization or after discharge) or the presence of diabetes.

Study Design

Design
RCT
Open-Label
Sample
4,041
Patients
Duration
3 yr
Median
Setting
Multicenter, international
Population Patients with STEMI and multivessel coronary artery disease who had undergone successful culprit-lesion primary percutaneous coronary intervention.
Intervention Complete revascularization consisting of angiography-guided PCI of all suitable nonculprit lesions.
Comparator Culprit-lesion-only percutaneous coronary intervention (guideline-directed medical therapy alone).
Outcome Composite of cardiovascular death or new myocardial infarction; and composite of cardiovascular death, new myocardial infarction, or ischemia-driven revascularization.

Study Limitations

The trial was open-label, which introduces the possibility of bias in the assessment of ischemia-driven revascularization as a component of the second coprimary endpoint.
Patients with cardiogenic shock were excluded, limiting the generalizability of these findings to the most critically ill STEMI patients.
The study focused on angiography-guided PCI, so the benefits might differ if functional assessment (e.g., FFR) were used exclusively to determine lesion significance.
While the reduction in hard clinical outcomes (CV death or MI) is robust, the trial cannot definitively isolate whether the benefit is due to the prevention of future MI from nonculprit lesions or other mechanisms.

Clinical Significance

The COMPLETE trial provides high-quality evidence to shift clinical practice from a 'culprit-only' strategy to one of complete, staged revascularization for stable nonculprit lesions in patients with STEMI and multivessel coronary disease, providing a clear benefit for hard cardiovascular outcomes.

Historical Context

Prior to the COMPLETE trial, the management of nonculprit lesions in STEMI patients with multivessel disease was controversial, with previous smaller trials yielding conflicting results and primarily driving reductions in revascularization rather than hard endpoints like death or MI; COMPLETE was the largest trial to definitively establish the superiority of complete revascularization.

Guided Discussion

High-yield insights from every perspective

Med Student
Medical Student

In the context of the COMPLETE trial, what is the pathophysiological distinction between a 'culprit' lesion and a 'non-culprit' lesion in a patient presenting with an acute STEMI?

Key Response

A culprit lesion is the site of acute plaque rupture or erosion leading to total or subtotal coronary occlusion and subsequent myocardial infarction. Non-culprit lesions represent stable but significant atherosclerotic obstructions in other coronary arteries. Understanding this distinction is foundational for clinical reasoning, as it defines the difference between treating the immediate life-threatening event and managing the patient's overall burden of coronary artery disease.

Resident
Resident

The COMPLETE trial suggests a benefit for staged revascularization. How should a clinician decide the optimal timing for treating non-culprit lesions based on this study's protocol and results?

Key Response

In COMPLETE, non-culprit PCI was performed either during the index hospitalization or after discharge (median 1 day for the former, 19 days for the latter). The study showed that the benefit of complete revascularization was consistent regardless of whether the staged procedure occurred during the index stay or within 45 days of discharge, allowing for clinical flexibility based on patient stability and logistical factors.

Fellow
Fellow

How do the findings of the COMPLETE trial integrate with the results of the CULPRIT-SHOCK trial when managing a patient with multivessel disease and STEMI complicated by cardiogenic shock?

Key Response

It is critical to differentiate the stable STEMI population in COMPLETE from the shock population in CULPRIT-SHOCK. While COMPLETE supports routine staged complete revascularization for stable patients, CULPRIT-SHOCK demonstrated that immediate multivessel PCI in the setting of cardiogenic shock increases the risk of death or renal failure. Therefore, the 'complete' strategy should generally be staged and reserved for hemodynamically stable patients.

Attending
Attending

Considering the COMPLETE trial demonstrated a significant reduction in MI but not a statistically significant reduction in all-cause mortality, how do you incorporate these findings into your shared decision-making process for an elderly patient with significant comorbidities?

Key Response

The benefit in COMPLETE was driven primarily by a reduction in new myocardial infarctions (hazard ratio 0.68). In an elderly patient with high frailty or bleeding risk, the attending must weigh the 'preventive' benefit of avoiding a future MI against the procedural risks (stroke, contrast nephropathy, bleeding) of additional PCI, recognizing that the absolute mortality benefit may be minimal in patients with limited life expectancy.

Scholarly Review

Critical appraisal through the lens of expert reviewers and guideline development

PhD
PhD

The COMPLETE trial utilized a composite primary endpoint of cardiovascular death or myocardial infarction. From a methodological standpoint, how does the inclusion of 'ischemia-driven revascularization' in the secondary composite endpoint affect the interpretation of the trial's 'hard' clinical outcomes?

Key Response

Including soft endpoints like revascularization often inflates the treatment effect size because these endpoints are more frequent and prone to physician bias (especially in open-label trials). By separating the hard endpoint (CV death/MI) from the soft endpoint (ischemia-driven revascularization), COMPLETE provided robust evidence that the benefit extends to actual muscle-sparing outcomes rather than just reducing the physician's urge to fix known narrowings.

Journal Editor
Journal Editor

As a reviewer, what concerns would you raise regarding the potential for 'detection bias' in the COMPLETE trial, and how did the study design attempt to mitigate the risk of unblinded clinicians over-reporting events in the culprit-only group?

Key Response

Because the trial was open-label, clinicians knew which patients had residual disease. This could lead to a lower threshold for diagnosing MI or performing revascularization in the culprit-only group. To mitigate this, the trial used a blinded independent clinical events committee to adjudicate all suspected outcomes based on objective criteria (troponin levels, ECG changes), which is a critical standard for high-quality cardiovascular trials.

Guideline Committee
Guideline Committee

Following the COMPLETE trial, should the Class of Recommendation for non-culprit PCI in STEMI be upgraded from IIa to I in the ACC/AHA guidelines, and what specific level of evidence should be assigned?

Key Response

Prior to COMPLETE, guidelines (e.g., 2015 ACC/AHA update) gave a Class IIb or IIa recommendation for non-culprit PCI. Given that COMPLETE is a large-scale (4,000+ patients), multi-center, randomized controlled trial showing a clear reduction in hard endpoints (MI), it provides the 'Level A' evidence necessary to support a Class I recommendation (strong recommendation) for staged complete revascularization in stable STEMI patients with multivessel disease.

Clinical Landscape

Noteworthy Related Trials

2013

PRAMI Trial

n = 465 · NEJM

Tested

Preventive PCI of non-culprit stenoses

Population

Patients with STEMI and multivessel coronary artery disease

Comparator

Culprit-only PCI

Endpoint

Composite of cardiac death, nonfatal MI, or refractory angina

Key result: Preventive PCI of non-culprit lesions significantly reduced the risk of major adverse cardiac events compared with culprit-only PCI.
2015

CvLPRIT Trial

n = 296 · JACC

Tested

Complete revascularization during the index hospital admission

Population

Patients with STEMI and multivessel disease

Comparator

Culprit-only revascularization

Endpoint

Composite of all-cause mortality, recurrent MI, heart failure, and ischemia-driven revascularization at 12 months

Key result: Complete revascularization was associated with a significant reduction in the primary outcome compared to culprit-only treatment.
2015

DANAMI-3-PRIMULTI Trial

n = 627 · Lancet

Tested

FFR-guided complete revascularization

Population

Patients with STEMI and multivessel disease with non-culprit stenosis

Comparator

Conservative treatment (culprit-only)

Endpoint

Composite of cardiac death, nonfatal MI, or ischemia-driven revascularization of non-culprit lesions

Key result: FFR-guided complete revascularization significantly reduced the rate of repeat revascularization compared with conservative management.

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