CvLPRIT

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Gershlick et al. "Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease". J Am Coll Cardiol. 2015. 65(10):963-72.
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Clinical Question

Among patients undergoing percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI) and found to have multivessel disease on angiography, is culprit lesion-only revascularization superior to complete revascularization with regard to a primary composite outcome of death, nonfatal MI, heart failure, or repeat revascularization?

Bottom Line

Among patients undergoing PCI for STEMI and found to have multivessel disease on angiography, complete revascularization is associated with an 11% absolute reduction in major adverse cardiovascular outcomes (MACE) at 12 months compared to culprit lesion-only revascularization, driven by symmetric modest reductions in each component of the primary composite outcome.

Major Points

PCI is standard of care for STEMI and has an established mortality benefit in this disease. However, up to 30% of patients presenting with STEMI are found to have multivessel CAD with significant stenosis seen in one or more non-infarct-related arteries (N-IRA). It is unclear whether these lesions are simply incidental, in which the risks of intervening upon them after culprit vessel revascularization may outweigh the benefits, or whether these N-IRA lesions contribute to a pro-thrombotic milieu, in which intervention may reduce the risk of recurrent events. Older observational and registry studies suggest that multivessel revascularization either at the time of index PCI or within a short interval lead to either similar or worse outcomes. [1][2] However, these retrospective analyses are limited by confounding, as sicker patients may be more likely to undergo more aggressive intervention at the time of PCI. In addition, PCI technology has improved significantly since the time of these analyses and thus the risk profile of more complex intervention may be lower than previously suggested.

The 2015 Complete Versus Lesion-Only Primary PCI Trial (CvLPRIT) randomized 296 patients presenting with acute STEMI and found to have multivessel disease on index angiography to culprit lesion-only revascularization or complete revascularization (either at index PCI [67%] or staged procedure performed prior to hospital discharge [33%]) and assessed for a primary outcome of MACE (death, nonfatal MI, heart failure, or repeat revascularization). At 12 months, patients randomized to complete revascularization were found to have an 11% absolute reduction in MACE, driven symmetrically by reductions in each component of the primary outcome although no individual component reached statistical significance. There was no difference between groups in major safety outcomes including bleeding, contrast nephropathy, or stroke.

In addition to CvLPRIT, the similarly-designed PRAMI and DANAMI-3 PRIMULTI trials also suggested improved MACE rates with complete revasularization at the time of STEMI (or at a short interval). More recently, a meta-analysis including both CvLPRIT and PRAMI showed a 40% lower odds of MACE with complete revascularization, with a nonsignificant trend towards improved cardiovascular mortality. It is thought that intervention even upon non-culprit lesions may lead to pacification of an inflammatory milieu in the peri-STEMI anatomy that may lead to decreased risk of recurrent thrombosis and possible salutary effects on ischemic/stunned myocardium. On the strength of these findings, the 2015 ACC/AHA/SCAI guidelines on primary PCI for STEMI now include PCI of N-IRAs in "selected patients with STEMI and multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure" as a class IIb recommendation. A remaining question is whether complete revascularization at index PCI is superior to complete revascularization with a staged procedure, as both approaches were allowed in CvLPRIT.

Guidelines

Adapted from the 2015 Focused Update of the ACC/AHA/SCAI guidelines on primary PCI for STEMI

  • PCI of a non-infarct artery may be considered in selected patients with STEMI and multivessel disease who are hemodynamically stable, either at the time of primary PCI or as a planned staged procedure (Class IIb, Level of Evidence B-R)

Design

  • Multicenter, randomized, open-label, active-comparator trial
  • N=296
    • Target lesion-only revascularization (N=146)
    • Complete revascularization (N=150)
  • Setting: 7 UK centers
  • Enrollment: May 2011 - May 2014
  • Duration of follow-up: 12 months
  • Analysis: Intention-to-treat
  • Primary outcome: MACE (death, nonfatal MI, heart failure, repeat revascularization)

Population

Inclusion Criteria

  • Presentation with electrocardiographically confirmed STEMI
  • Presentation within 12 hours of symptom onset

Exclusion Criteria

  • Indication for (i.e., cardiogenic shock) or contraindication to complete revascularization
  • Previous MI
  • Prior CABG
  • Ventricular septal defect
  • Moderate to severe MR
  • CKD
  • Stent thrombosis

Baseline Characteristics

From the complete revascularization group

  • Demographics: Age 64.6, male 85.3%
  • Co-morbidities: DM 12.9%, HTN 36.6%, HLD 27.9%, smoker 34.3%, previous MI 4.8%, previous PCI 4.1%, Killip class II/III 6.8%, GFR < 30 0.7%
  • MI characteristics: Anterior MI 36.0%, N-IRA stenosis > 70% 87.3%, 2-vessel CAD 79.3%, 3-vessel CAD 20.7%, maximal hs-TnT elevation 985, EF 45.8%, radial access 76.7%, stents placed 3
  • Medications: ASA 99.3%, P2Y12 inhibitor 94.5%, GPI 31.7%, bivalirudin 56.8%, DES 95.9%, BB 93.2%, ACEi/ARB 96.6%, statin 100%, aldosterone antagonist 6.1%, other antianginal 37.4%, loop diuretic 10.2%

Interventions

  • After electrocardiographic confirmation of STEMI, patients were given contemporary dual-antiplatelet therapy
  • Randomization occurred after angiography but before IRA PCI
  • Patients meeting criteria then randomized to complete revascularization or IRA only revascularization
    • Randomization stratified by infarct location (anterior/nonanterior) and symptom-onset (≤ 3h or > 3h)
  • PCI was undertaken according to current guideline recommendations and operators' routine practice and could include aspiration thrombectomy, heparin, bivalirudin, or glycoprotein IIb/IIIa inhibitor use
  • Preferential use of DES
  • Patients randomized to N-IRA PCI preferentially underwent N-IRA PCI immediately after IRA PCI in the same procedure, although a staged procedure during the same hospitalization could be performed at the operators' discretion
  • All patients underwent myocardial perfusion scintigraphy (MPS) at 6 weeks after discharge to assess for ischemia
  • Telephone follow-up performed at 6 months for adverse events. Patients seen at 9-12 months to document MACE
  • Clinicians blinded to randomization group adjudicated all MACE and safety endpoints

Outcomes

Presented as complete revascularization vs. IRA-only revascularization

Primary Outcome

Death, nonfatal MI, heart failure, repeat revascularization
15 (10.0%) vs. 31 (21.2%) [HR 0.45, 95% CI 0.24-0.84, p=0.009]

Secondary Outcomes

Death
2 (1.3%) vs. 6 (4.1%) [HR 0.32, 95% CI 0.06-1.60, p=0.14]
Nonfatal MI
2 (1.3%) vs. 4 (2.7%) [HR 0.48, 95% CI 0.09-2.62, p=0.39]
Heart failure
4 (2.7%) vs. 9 (6.2%) [HR 0.43, 95% CI 0.13-1.39, p=0.14]
Repeat revascularization
7 (4.7%) vs. 12 (8.2%) [HR 0.55, 95% CI 0.22-1.39, p=0.20]

Subgroup Analysis

Subgroup analyses suggested similar benefit to complete revascularization in all subgroups including stratification by sex, age, and double- vs. triple-vessel CAD

Adverse Events

Stroke
2 (1.3%) vs. 2 (1.4%) [HR 0.95, 95% CI 0.13-6.77, p=0.96]
Major bleed
4 (2.7%) vs. 7 (4.8%) [HR 0.55, 95% CI 0.16-1.87, p=0.34]
Contrast-induced nephropathy
2 (1.4%) vs. 2 (1.4%) [HR 0.94, 95% CI 0.13-6.75, p=0.95]

Criticisms

  • Trial was underpowered to detect key secondary endpoints including all-cause mortality
  • Since this was not protocolized, it remains unclear whether complete revascularization with staged PCI is superior to complete revascularization at the index PCI
  • Open-label design allows for possible bias although "harder" endpoints of death and MI showed similar improvement to more subjective endpoints such as repeat revascularization. This was also partially mitigated by outcome adjudication performed by blinded assessors.

Funding

  • Funding organizations had no role in the conduct, analysis, or reporting of the study
  • Authors with multiple ties to industry

Further Reading

  1. Hannan EL et al. Culprit vessel percutaneous coronary intervention versus multivessel and staged percutaneous coronary intervention for ST-segment elevation myocardial infarction patients with multivessel disease. JACC Cardiovasc Interv 2010. 3:22-31.
  2. Cavender MA et al. Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry). Am. J. Cardiol. 2009. 104:507-13.