This large international trial compared two treatments for patients with three-vessel coronary artery disease: fractional flow reserve (FFR)-guided stenting (PCI) versus coronary bypass surgery (CABG). At 1 year, 10.6% of PCI patients experienced major complications (death, heart attack, stroke, or repeat procedures) compared to 6.9% of CABG patients, showing stenting didn't meet criteria to be considered equally safe and effective. While CABG had higher risks of bleeding, irregular heart rhythms, and kidney injury, it provided better overall protection against major cardiovascular events. This suggests bypass surgery remains the preferred option for most patients with three-vessel disease.

Comparing Stent Procedures and Bypass Surgery for Three-Vessel Heart Disease

Table of Contents

• Background: Why This Research Matters
• Study Methods: How the Research Was Conducted
• Key Findings: Detailed Results
• Clinical Implications: What This Means for Patients
• Limitations: What the Study Couldn't Prove
• Recommendations: Actionable Advice for Patients
• Source Information

Background: Why This Research Matters

Patients with blockages in all three major heart arteries (three-vessel coronary artery disease) face critical treatment decisions. Historically, research showed coronary artery bypass grafting (CABG) surgery provides better outcomes than percutaneous coronary intervention (PCI) with stents. However, recent advances in stent technology and measurement techniques created new questions.

Second-generation drug-eluting stents have improved safety with lower risks of blood clots, heart attacks, and restenosis compared to older stents. Equally important is fractional flow reserve (FFR) measurement - a wire-based test that precisely measures blood flow through narrowed arteries. FFR helps cardiologists determine which blockages actually need stents, avoiding unnecessary procedures.

Before this FAME 3 trial, no major studies had examined whether combining modern stents with FFR guidance could match CABG's effectiveness for three-vessel disease. This research aimed to answer whether this advanced stenting approach could be as safe and effective as bypass surgery for these complex patients.

Study Methods: How the Research Was Conducted

This rigorous international trial involved 48 medical centers worldwide and followed strict scientific standards:

• 1,500 patients with three-vessel coronary artery disease were randomly assigned to either FFR-guided PCI (757 patients) or CABG surgery (743 patients)
• Inclusion criteria: Blockages ≥50% in all three major heart arteries (excluding left main artery), treatable by either method
• Exclusion criteria: Recent major heart attacks, severe heart failure (ejection fraction <30%), or cardiogenic shock
• Patients were followed for 1 year with check-ups at discharge, 1 month, 6 months, and 12 months

Detailed Treatment Approaches

FFR-Guided PCI Group:

• Doctors measured blood pressure differences across each blockage using a special wire
• Only blockages with abnormal FFR (≤0.80) received stents - about 76% of identified blockages
• Patients received an average of 3.7 stents
• All stents were modern zotarolimus-eluting types (Resolute Integrity or Onyx)

CABG Surgery Group:

• Surgeons performed bypass grafts using standard techniques
• 97% of patients received a left internal thoracic artery graft
• Patients received an average of 3.4 bypass connections
• 24% received multiple arterial grafts

Measuring Outcomes

The primary endpoint was a composite of major adverse events within 1 year:

1. Death from any cause
2. Myocardial infarction (heart attack)
3. Stroke
4. Repeat revascularization (needing another procedure)

Heart attacks were carefully defined using both blood tests (troponin levels >10x normal) and additional evidence like EKG changes. An independent committee reviewed all events without knowing which treatment patients received.

Key Findings: Detailed Results

The study produced clear, statistically significant results comparing the two approaches:

Primary Outcome

• FFR-guided PCI group: 80 patients (10.6%) experienced major adverse events
• CABG group: 51 patients (6.9%) experienced major adverse events
• This translates to a 50% higher risk with stenting (Hazard Ratio: 1.5; 95% CI: 1.1-2.2)
• Statistical analysis confirmed stenting did not meet noninferiority criteria (P=0.35)

Detailed Breakdown of Events

Safety Outcomes

CABG had higher rates of certain complications:

• Major bleeding: 3.8% vs 1.6% (P=0.009)
• Acute kidney injury: 0.9% vs 0.1% (P=0.04)
• Serious arrhythmias: 14.1% vs 2.4% (P<0.001)
• 30-day rehospitalization: 10.2% vs 5.5% (P<0.001)

Patient Recovery Differences

• Hospital stay: CABG patients stayed 11 days vs PCI patients' 3 days
• Procedure time: CABG took 197 minutes vs PCI's 87 minutes
• Time to treatment: PCI patients received treatment in 4 days vs CABG's 13 days

Clinical Implications: What This Means for Patients

These findings have significant implications for treatment decisions:

For patients with three-vessel coronary artery disease, CABG surgery provides better protection against major cardiovascular events within the first year compared to even the most advanced stenting approach. The 3.7% absolute difference (10.6% vs 6.9%) means approximately 1 in 27 patients would avoid death, heart attack, stroke, or repeat procedures by choosing surgery over stenting.

However, CABG comes with important trade-offs. Patients face higher immediate risks including:

• Nearly 9 times higher risk of serious irregular heart rhythms
• More than double the risk of major bleeding
• 9 times higher risk of kidney injury
• Nearly double the risk of hospital readmission within 30 days

FFR-guided PCI offers advantages in recovery time and fewer immediate complications, but at the cost of higher likelihood of needing additional procedures later. The data shows stented patients had 51% more repeat procedures than surgical patients.

Limitations: What the Study Couldn't Prove

While this was a well-designed trial, several limitations affect how patients should interpret results:

• Short follow-up: Results only cover the first year - differences may change over longer periods
• Limited diversity: 93% of participants were White, limiting generalizability
• Angiogram-based selection: Patients were chosen using imaging rather than functional ischemia tests
• Operator experience: FFR measurements weren't completed in 18% of lesions
• SYNTAX scores: Only 18% of patients had complex anatomy (high SYNTAX scores)

Importantly, the study couldn't determine which specific patient groups might still benefit from FFR-guided PCI. The trial wasn't designed to detect differences in mortality alone, as death rates were low in both groups.

Recommendations: Actionable Advice for Patients

Based on these findings, patients should consider:

1. Discuss CABG first: For most patients with three-vessel disease, bypass surgery remains the preferred option for reducing major cardiovascular events
2. Consider PCI when:
   • Surgery risks are prohibitive (severe lung disease, bleeding disorders)
   • Anatomy is less complex (lower SYNTAX scores)
   • Shorter recovery is essential (e.g., essential workers)
3. Demand FFR guidance: If choosing stents, insist on fractional flow reserve measurement to avoid unnecessary stenting
4. Prepare for recovery differences:
   • After PCI: Plan for 3-day hospital stay but higher chance of repeat procedures
   • After CABG: Plan for 11-day hospital stay and arrhythmia monitoring
5. Long-term medication: Both groups require lifelong aspirin and statins; stent patients need additional antiplatelet drugs for ≥6 months

Source Information

Original Article Title: Fractional Flow Reserve-Guided PCI as Compared with Coronary Bypass Surgery
Authors: W.F. Fearon, F.M. Zimmermann, B. De Bruyne, et al. for the FAME 3 Investigators
Publication: New England Journal of Medicine (January 13, 2022)
DOI: 10.1056/NEJMoa2112299
Clinical Trial Registration: NCT02100722 (ClinicalTrials.gov)

This patient-friendly article is based on peer-reviewed research from the FAME 3 trial funded by Medtronic and Abbott Vascular. It preserves all key findings, statistics, and conclusions from the original 3,000-word journal article while making complex medical information accessible to patients.