PRAMI

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Wald DS, et al. "Randomized trial of preventative angioplasty in myocardial infarction". The New England Journal of Medicine. 2013. 369(12):1115-1123.
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Clinical Question

Among patients with STEMI undergoing PCI, does preventative PCI to non-infarct arteries with ≥50% stenosis reduce CV mortality, non-fatal MI, or refractory angina when compared to no preventative PCI?

Bottom Line

Preventative PCI to non-infarct arteries with ≥50% stenosis after PCI to the infarct artery in patients with STEMI reduces rates of CV mortality, non-fatal MI, or refractory angina when compared to no preventative PCI.

Major Points

The 2007 COURAGE trial demonstrated that preventative PCI plus optimal medical therapy (OMT) did not differ from OMT alone in patients with stable CAD for all-cause mortality and non-fatal MI. As such, current guidelines recommend OMT-focused therapy for patients with CAD that would not clearly benefit from revascularization.[1] In contrast, patients presenting with STEMI clearly benefit from early PCI to the infarct artery.[2] However, little is understood about subsequent treatment of non-infarct atheromas of substantial size.[3] 2013 ACC/AHA STEMI guidelines recommend against PCI to non-infarct artery in patients with STEMI who are hemodynamically stable (class III level B).[4]

The 2013 Preventative Angioplasty in Acute Myocardial Infarction (PRAMI) trial randomized 465 patients with STEMI undergoing infarct artery-directed PCI to either immediate preventative PCI to non-infarct arteries with atheromas ≥50% stenosis or no preventative PCI. The trial was stopped early at a mean follow-up of 23 months as an interim analysis demonstrated benefit for preventative PCI. Specifically, the preventative PCI group had lower rates of the primary outcome of CV mortality, non-fatal MI, or refractory angina (HR 0.35). This was driven by significant reduction in repeat revascularization, non-fatal MI, and refractory angina. Additionally, the composite endpoint for CV mortality or non-fatal MI gained significance.

Guidelines

As of November 2013, no guidelines have been published that reflect the results of this trial.

Design

  • Multicenter, prospective, randomized, single blinded trial
  • N=465
    • Preventative PCI (n=234)
    • No preventative PCI (n=231)
  • Setting: 5 centers in the UK
  • Enrollment: 2008-2013 (stopped early)
  • Mean follow-up: 23 months
  • Analysis: Intention-to-treat
  • Primary outcome: CV mortality, non-fatal MI, or refractory angina

Population

Inclusion Criteria

  • STEMI in patients of any age multivessel CAD identified at the time of PCI
  • Successful treatment of infarct artery
  • Stenosis ≥50% and thought to be treatable
  • Equipoise for treating the non-infarct artery as well as the infarct artery

Exclusion Criteria

  • Cardiogenic shock
  • Unable to consent to randomization
  • Prior CABG
  • Non-infarct stenosis ≥50% of LM or ostia of both LAD and circumflex
  • Non-infarct stenosis was total occlusion

Baseline Characteristics

From the preventative PCI group.

  • Demographics: Age 62 years, male 76%
  • PMH: DM 15%, HTN 40%, current smoker 50%, CVA 4%, MI 8%
  • Baseline health data: BP 136/81
  • Infarct location: Anterior 29%, inferior 66%, lateral 4%
  • LBBB: 1%
  • Stenotic arteries:
    • 2: 61%
    • 3: 39%
    • Proximal or mid portion of LAD: 26%
  • PCI details:
    • Infarct stent: Bare metal 37%, drug eluting 63%, no stent <1%
      • Preventative stent (preventative group only): Bare metal 25%, drug eluting 71%, no stent 5%
    • Medical therapy:
      • ASA: 100%
      • Clopidogrel, prasugrel, or ticagrelor: 100%
      • Statin: 85%
      • Beta blocker: 88%
      • ACE-inhibitor or ARB: 93%
      • CCB: 12%
      • Nitrate: 16%
      • GP IIb/IIIa inhibitor 76%
      • Bivalirudin 3%

Interventions

  • Following completion of infarct PCI, patients were randomized to a group:
    • Preventative PCI - PCI to non-infarct arteries with ≥50% stenoses
    • No preventative PCI - Usual PCI care
  • Other clinical management decisions were left to the treating physician
  • Discouragement of staged PCI
  • If ongoing chest pain not controlled with medical therapy was required to undergo objective assessment of ischemia with repeat PCI occurring only if ischemia was found

Outcomes

Presented as preventative PCI vs. no preventative PCI.

Primary Outcome

CV mortality, non-fatal MI, or refractory angina
21 vs. 53 events (HR 0.35; 95% CI 0.21-0.58; P<0.001)

Secondary Outcomes

Non-cardiac mortality
8 vs. 6 events (HR 1.10; 95% CI 0.38-3.18; P=0.86)
Repeat revascularization
16 vs. 46 events (HR 0.30; 95% CI 0.17-0.56; P<0.001)
CV mortality or non-fatal MI
11 vs. 27 events (HR 0.36; 95% CI 0.18-0.73; P=0.004)
CV mortality
4 vs. 10 events (HR 0.34; 95% CI 0.11-1.08; P=0.07)
Non-fatal MI
7 vs. 20 events (HR 0.32; 95% CI 0.13-0.75; P=0.009)
Refractory angina
12 vs. 30 events (HR 0.35; 95% CI 0.18-0.69; P=0.002)

Subgroup Analysis

There was no difference for the primary endpoint when broken down by gender, age < or ≥65 years, infarct location, or number of arteries with stenosis.

Criticisms

  • Did not use revascularization as a primary outcome
  • Unclear if similar outcomes in patients with NSTEMI
  • Unclear if preventative PCI best occurs during emergent PCI or as a second procedure[5]
  • Unclear if a modality like FFR would further enhance the outcomes of this trial[5]

Funding

  • Barts and the London Charity
  • Authors with multiple financial disclosures

Further Reading

  1. Fihn SD, et al. "2012 ACCF/AHA/ACP/AATS/PCNA/SCAI/STS guidelines for the diagnosis and management of patients with stable ischemic heart disease: Executive summary." Circulation. 2012:126(25):3097-3137.
  2. Huynh T, et al. "Comparison of primary percutaneous coronary intervention and fibrinolytic therapy in ST-segment-elevation myocardial infarction: Bayesian hierarchical meta-analyses of randomized controlled trials and observational studies." Circulation. 2009;119(24):3101-3109.
  3. O'Gara PT, et al. "2013 ACCF/AHA guidelines for the management of ST-elevation myocardial infarction: A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines." Circulation. 2013;127(4):e362-425.
  4. O'Gara PT, et al. "2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines." Circulation. 2013;127(4):e362-e425.
  5. 5.0 5.1 Mauri, L. "Editorial: Nonculprit lesions - Innocent or guilty by association." The New England Journal of Medicine. 2013;369:1166-1167.