PRAMI

Published

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

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. In contrast, patients presenting with STEMI clearly benefit from early PCI to the infarct artery. However, little is understood about subsequent treatment of non-infarct atheromas of substantial size. 2013 ACC/AHA STEMI guidelines recommend against PCI to non-infarct artery in patients with STEMI who are hemodynamically stable (class III level B).

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

In the 2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction, the reccomendation for PCI of multivesel disease was upgraded from class III: harm to IIb (level of evidence B-R), as four RCTs have suggested since last guidelines in 2013 that a strategy of multivessel PCI, either at the time of primary PCI or as a planned, staged procedure, may be beneficial and safe in selected patients with STEMI. These RCT are: PRAMI (Preventive Angioplasty in Acute Myocardial Infarction); the CvLPRIT (Complete Versus Culprit-Lesion Only Primary PCI) trial; the DANAMI 3 PRIMULTI (Third Danish Study of Optimal Acute Treatment of Patients with ST-segment Elevation Myocardial Infarction) trial and the PRAGUE-13 (Primary Angioplasty in Patients Transferred From General Community Hospitals to Specialized PTCA Units With or Without Emergency Thrombolysis) trial. The writing committee emphasizes that this change should not be interpreted as endorsing the routine performance of multivessel PCI in all patients with STEMI and multivessel disease. Rather, when considering the indications for and timing of multivessel PCI, physicians should integrate clinical data, lesion severity/complexity, and risk of contrast nephropathy to determine the optimal strategy.

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
• Unclear if a modality like FFR would further enhance the outcomes of this trial

Funding

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