The REVIVED Trial: PCI in Patients with Severe Ischemic Left Ventricular Systolic Dysfunction?

Background: Coronary artery disease can result in hibernating myocardium (chronic myocardial contractile dysfunction) due to ischemia.  The theory is that there is reduced coronary blood flow and increased myocardial demand resulting in impaired contractility. Whether reversal of myocardial hibernation by coronary revascularization is possible and can improve outcomes is debatable.  The STICH trial [2] compared CABG plus optimal medical therapy compared to medical therapy alone.  The incidence of death from any cause (the primary outcome) at 5 years was similar between groups, but the CABG group had more early death compared to medical therapy alone.  Revascularization can be performed by coronary artery bypass grafting (CABG), or by percutaneous coronary intervention (PCI). There is limited evidence on whether PCI in addition to medical management is superior to medical management alone.

Paper: Perera D et al. Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction. NEJM 2022. PMID: 36027563 [Access on Read by QxMD]

Clinical Question: Does revascularization by percutaneous coronary intervention (PCI) improve event-free survival and left ventricular function in patients with severe ischemic left ventricular systolic dysfunction compared to optimal medical therapy alone?

What They Did:

• Revascularization for Ischemic Ventricular Dysfunction (REVIVED)
• Prospective, multicenter, randomized, open-label clinical trial
• Patients with left ventricular ejection fraction of ≤35%, extensive coronary disease amendable to PCI, and demonstrable myocardial viability randomized to:
  • PCI Group: PCI + Optimal Medical Therapy (OMT)
  • OMT Group: Optimal Medical Therapy Alone
    • Included pharmacologic and device therapy

Outcomes:

• Primary: Composite outcome of death from any cause or hospitalization for heart failure over a 24 month follow up period
• Major Secondary Outcomes:
  • Left ventricular ejection fraction at 6 and 12 months
  • Quality of life scores

Inclusion:

• Left ventricular ejection fraction ≤35%
• Extensive coronary artery disease
• Demonstrable viability in at least four dysfunctional myocardial segments amendable to revascularization with PCI

Exclusion:

• Acute myocardial infarction in 4 weeks prior to randomization
• Acute decompensated heart failure
• Sustained ventricular arrhythmias within 72 hours prior to randomization

Results:

• 700 patients randomized
  • Average LVEF: 27%
  • Median follow up duration was 41 months (Range 28 to 60 months) after randomization
• Composite Primary Outcome (Over a Median of 41mos):
  • PCI: 37.2%
  • OMT: 38.0%
  • HR 0.99; 95% CI 0.78 to 1.27; p = 0.96
  • Also no difference in the individual components of the composite outcome
• Left ventricular ejection fraction at 6 months similar (Mean diff -1.6%; 95% CI -3.7 to 0.5)
• Left ventricular ejection fraction at 12 months similar (Mean diff 0.9%; 95% CI -1.7 to 3.4)
• Quality of life scores at 6 and 12 months appeared to favor the PCI group, but the difference was diminished at 24 months

Strengths:

• Asks a clinically important question in a high-risk group of patients
• Groups fairly balanced in terms of age, race, BMI, NYHA functional class, CCS angina class, pharmacologic therapy and devices at baseline
• Almost no loss to follow up with 99.1% of enrolled patients having been evaluated for the primary outcome
• All hospitalizations for heart failure were adjudicated in a blinded fashion by an independent events committee
• Left ventricular ejection fraction was assessed in a blinded fashion at the cor laboratory as well

Limitations:

• Open-label (unblinded) study design could have impacts on subjective outcomes such as quality of life
• Most patients in this trial had little to no angina at enrollment which limits generalizability to patients having angina or acute coronary syndromes
• >90% of patients were Caucasian which could limit generalizability to other ethnicities
• Some baseline differences favored the PCI group
• Primary outcome was a composite outcome that are not of equal value (hospitalization vs death)

Discussion:

• Although the incidence of death from any cause of hospitalization for heart failure did not differ significantly between groups, there was an early benefit of PCI in terms of quality of life. This benefit diminished over time most likely due to the progressive improvement in the optimal medical therapy group
• One other point of note is that acute myocardial infarction was similar between the two groups overall (PCI 10.7% vs OMT 10.8%) but when looking at periprocedural acute MI vs spontaneous MI there was a difference:
  • Periprocedural: PCI 37.8% vs OMT 0%
  • Spontaneous: PCI 48.7% vs OMI 86.8%
• The STICH Trial [2]:
  • Enrolled 1200 patients with ischemic cardiomyopathy and reduced ejection fraction
  • The incidence of death from any cause (the primary outcome) at 5 years was similar in the group assigned to undergo CABG and the group assigned to receive medical therapy alone
  • CABG group had more early death compared to medical therapy alone, but in the patients who survived there was a benefit over time with these patients more likely to be alive after 10 years compared to medical therapy alone
    • CABG reduced the most common modes of death: Sudden death (HR 0.73; 95% CI 0.44 to 0.99; p = 0.041) and fatal pump failure events (HR 0.64; 95% CI 0.41 to 1.00; p = 0.05)
      • The protective effect of CABG occurred after 24 months
    • Deaths post CABG were increased (HR 3.11; 95% CI 1.47 to 6.60)
    • Fatal MI deaths were lower with CABG (HR 0.07;95% CI 0.01 to 0.57)
  • Bottom Line: Post CABG deaths were increased early, but fatal MI deaths were decreased post early CABG, HOWEVER the protective effects for sudden death and fatal pump failure occurred after a 24-month period on average

Author Conclusion: “Among patients with severe ischemic left ventricular systolic dysfunction who received optimal medical therapy, revascularization by PCI did not result in a lower incidence of death from any cause or hospitalization for heart failure.”

Clinical Take Home Point: In this trial of adult patients with severe left ventricular systolic dysfunction, extensive coronary disease, and dysfunctional but viable myocardium the addition of PCI to optimal medical therapy did not lower the incidence of death from any cause or hospitalizations for heart failure, improvement in left ventricular ejection fraction, or a sustained difference in quality of life at a median of 3.4 years.

References:

1. Perera D et al. Percutaneous Revascularization for Ischemic Left Ventricular Dysfunction. NEJM 2022. PMID: 36027563 [Access on Read by QxMD]
2. Carson P et al. The STICH Trial (Surgical Treatment for Ischemic Heart Failure): Mode-of-Death Results. JACC Heart Fail 2013. PMID: 24621972

Post Peer Reviewed By: Anand Swaminathan, MD (Twitter: @EMSwami)