COMPLETE

Incomplete

Mehta SR, et al. "Complete Revascularization with Multivessel PCI for Myocardial Infarction". The New England Journal of Medicine. 2019. 381(15):1411-1421.
PubMed • Full text • PDF

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Clinical Question

In patients with STEMI and multivessel coronary artery disease, does PCI of non-culprit lesions reduce the risk of cardiovascular death and myocardial infarction?

Bottom Line

For patients with STEMI and multivessel coronary artery disease, complete revascularization compared to culprit-lesion-only revascularization led to a 26% lower risk in the coprimary composite outcome of cardiovascular death and myocardial infarction, driven by a 32% lower risk of new myocardial infarction. Complete revascularization also led to a 49% lower risk in the second coprimary composite outcome of cardiovascular death, myocardial infarction, and ischemia-driven revascularization at 3 years follow-up.

Major Points

Primary PCI is the established treatment of choice for coronary reperfusion in STEMI for those who can access it in a timely manner. Up to one-half of patients who present with STEMI are found to have multivessel coronary artery disease at angiography and has been associated with increased mortality. There have been a range of proposed strategies for the management of non-culprit lesions (lesions remote to the area of infarction) including PCI at the time of culprit primary PCI, delayed PCI, CABG, or optimal medical therapy.

Several studies have explored the preferred approach in managing non-culprit lesions however the evidence has been conflicting. The previous meta-analysis has suggested a potential mortality benefit and reduced repeat PCI with staged multivessel PCI, however, this included largely non-randomised trials. Previous smaller randomized trials including the PRAMI, CvLPRIT and DANAMI-3 PRIMULTI trials, comparing complete and culprit-only revascularization have been mostly been supportive of complete revascularization but had various limitations. Criticisms included having composite outcomes driven by repeat revascularization or refractory angina, as well as having a small number of total events. The COMPLETE trial, therefore, aimed to address the need for a large randomized trial with hard clinical endpoints.

COMPLETE randomized 4041 patients with STEMI and multivessel coronary artery disease who had received successful culprit lesion primary PCI to either no further revascularization or complete revascularization of all further angiographically significant non-culprit lesions, either during or after the index hospitalization. At a median of 3 years follow-up, there was a 2.7% absolute reduction in coprimary outcome of cardiovascular death and new MI, as well as 7.8% absolute reduction in cardiovascular death, new MI, and ischemia-driven revascularization, in the complete revascularization group. The outcome was consistent across both stratified groups (complete revascularization during the index hospitalization or within 45 days of randomization). These conclusive trial results have subsequently led to recommendations that complete revascularization of nonculprit lesions in STEMI patients be adopted in guidelines, particularly for patients with similar characteristics as those included in the trial.

Guidelines

No guidelines reflect the results of this trial as of August 2020.

Design

• Randomized, open-label, multicenter trial
• N=4041
  • Complete revascularization (n=2016)
  • Culprit-lesion-only revascularization (n=2025)
• Setting: 140 centers in 31 countries
• Enrollment: February 2013 to March 2017
• Follow-up: Mean 36.2 months; median 35.8 months (interquartile range, 27.6 to 44.3)
• Analysis: Intention-to-treat
• Primary end points:
  • Composite outcome of death from cardiovascular cause or new myocardial infarction
  • Composite outcome of death from cardiovascular cause, new myocardial infarction, or ischemia-driven revascularization

Population

Inclusion Criteria

• Enrolled within 72 hours of successful PCI of culprit lesion for STEMI
• Multivessel CAD defined as at least 1 additional non-culprit lesion that is:
  • at least 2.5mm in diameter (and not stented as part of the index PCI), AND
  • is amenable to treatment with PCI, AND
  • at least 70% diameter stenosis by visual estimation or 50-69% diameter stenosis by visual estimation plus FFR < 0.80

Exclusion Criteria

• Intent to revascularize non-culprit lesions regardless of study enrollment
• Planned surgical revascularization
• Non-cardiovascular co-morbidity with estimated life expectancy <5 years
• Any medical, geographic, or social factor that would limit the ability to follow up for 5 years
• Prior CABG

Baseline Characteristics

From the complete revascularization group.

• Mean age: 61.6 +/- 10.7 years
• Male sex: 80.5%
• Medical history
  • Hypertension: 48.7%
  • Diabetes mellitus: 19.1%
  • Dyslipidemia: 37.9%
  • Previous MI: 7.3%
  • Previous PCI: 7.0%
  • Previous stroke: 3.2%
  • Chronic renal insufficiency: 2.0%
• Time from symptom onset to index PCI
  • <6 hr: 69.4%
  • 6-12 hr: 16.1%
  • >12 hr: 14.5 %
• Killip class >II: 10.6%
• Hemoglobin A1c: 6.3 +/- 1.6
• Peak creatinine (umol/L): 84.7 +/- 30.8
• Medications at discharge
  • Aspirin: 99.8%
  • P2Y12 inhibitor
    • Any: 99.4%
    • Ticagrelor: 64.4%
    • Prasugrel: 9.6%
    • Clopidogrel 25.6%
  • Beta-blocker: 88.1%
  • ACEi/ARB: 85.5%
  • ARB: 33%
  • Calcium antagonist: 26%
  • Beta-blocker: 18%
  • Statin: 98.2%
• Index procedure for STEMI
  • Primary PCI: 91.9%
  • Pharmacoinvasive PCI: 3.2%
  • Rescue PCI: 4.9%
• Radial access: 80.8%
• Thrombus aspiration: 24.2%
• SYNTAX score
  • Culprit lesion-specific score: 8.8 +/- 5.3
  • Nonculprit lesion-specific score: 4.6 +/- 2.8
  • Baseline score, including culprit lesion: 16.3 +/- 6.8
  • Residual score, after index PCI: 7.2 +/- 4.9
• Location of culprit lesion
  • Left main coronary artery: 0.2%
  • Left anterior descending artery: 34.4%
  • Left circumflex artery: 18.0%
  • Right coronary artery: 47.4%
• Number of residual diseased vessels
  • 1: 76.1%
  • ≥2: 23.9%
• Location of nonculprit lesions
  • Left main coronary artery: 0.4%
  • Left anterior descending artery: 38.0%
  • Left circumflex artery: 36.4%
  • Right coronary artery: 25.3%
• Diameter of vessel with nonculprit lesion: 2.8 +/- 0.5
• Nonculprit lesion stenosis by visual estimation
  • 50-69% with FFR less than or equal to 0.80: 0.8%
  • 70-79%: 41.3%
  • 80-89%: 33.5%
  • 90-99%: 22.3%
  • 100%: 2.1%

Interventions

After successful culprit-lesion PCI patients were randomized, stratified according to center and intended timing of nonculprit PCI, to either:

• Complete revascularization strategy with routine staged PCI of all suitable nonculprit lesions (everolimus-eluting stents were strongly recommended), OR
• Culprit-lesion only strategy with optimal medical therapy alone (DAPT with aspirin and ticagrelor for at least 1 year, statin, ACEi or ARB, MRA, and beta-blockers were recommended).

Outcomes

Comparisons are complete revascularization vs. optimal medical therapy.

Primary Outcome

Death from cardiovascular cause or new myocardial infarction

7.8% vs. 10.5% (HR 0.74; 95% CI 0.60 to 0.91; p=0.004)

Death from cardiovascular cause, new myocardial infarction, or ischemia-driven revascularization

8.9% vs. 16.7% (HR 0.51; 95% CI 0.43 to 0.61; p<0.001)

Secondary Outcomes

Death from cardiovascular cause, new myocardial infarction, ischemia-driven revascularization, unstable angina, or NYHA class IV heart failure

13.5% vs. 21.0% (HR 0.62; 95% CI 0.53 to 0.72)

Myocardial infarction

5.4% vs. 7.9% (HR 0.68; 95% CI 0.53 to 0.86)

Ischemia-driven revascularization

1.4% vs. 7.9% (HR 0.18; 95% CI 0.12 to 0.26)

Unstable angina

3.5% vs. 6.4% (HR 0.53; 95% CI 0.40 to 0.71)

Death from cardiovascular causes

2.9% vs. 3.2% (HR 0.93; 95% CI 0.65 to 1.32)

Death from any cause

4.8% vs. 5.2% (HR 0.91; 95% CI 0.69 to 1.20)

Safety and Other Outcomes

Major bleeding

2.9% vs. 2.2% (HR 1.33; 95% CI 0.90 to 1.97)

Contrast-associated acute kidney injury

1.5% vs. 0.9% (HR 1.59; 95% CI 0.89 to 2.84)

Stroke

1.9% vs. 1.4% (HR 1.31; 95% CI 0.81 to 2.31)

NYHA class IV heart failure

2.9% vs. 2.8% (HR 1.04; 95% CI 0.72 to 1.50)

Stent thrombosis

1.3% vs. 0.9% (HR 1.38; 95% CI 0.76 to 2.49)

Subgroup Analysis

• No significant difference in coprimary outcomes in prespecified subgroups (timing of nonculprit lesions PCI, nonculprit involving proximal or middle LAD, nonculprit with stenosis >80% on visual or >60% on lab assessment, residual SYNTAX score, sex, age, LVEF, diabetes, type of P2Y12 inhibitor, type of PCI, Killip class, type of stent).

• No significant difference between treatment groups in safety and other outcomes (major bleeding, stroke, or stent thrombosis).

Adverse Events

No adverse events other than the outcomes listed above were reported.

Criticisms

• Relatively low SYNTAX score for non-culprit lesions enrolled
• High proportion of patients receiving clopidogrel
• The trial did not include patients in cardiogenic shock, limiting generalizability to that population. See CULPRIT-SHOCK
• All non-culprit lesion PCI was performed in a staged fashion rather than during the index procedure
• Optimal timing of staged non-culprit lesion PCI remains unclear

Funding

The study was funded by the Canadian Institutes of Health Research, AstraZeneca, Boston Scientific, and the Population Health Research Institute.

Multiple authors with multiple disclosures.