Article Identification

  • Article Title: Prophylactic Implantation of a Defibrillator in Patients with Myocardial Infarction and Reduced Ejection Fraction
  • Citation: Moss AJ, et al. N Engl J Med. 2002;346(12):877-883.
  • DOI/PMID: PMID: 11801510

Quick Reference Summary

  • Primary Outcome Measures: The study evaluated all-cause mortality in patients receiving an implantable defibrillator (ICD) versus conventional medical therapy.
  • Main Results: Over an average follow-up of 20 months, mortality was 19.8% in the conventional-therapy group compared to 14.2% in the defibrillator group (HR=0.69, 95% CI: 0.51–0.93; P=0.016), indicating a 31% reduction in the risk of death with ICD therapy.

Core Clinical Question

Does the prophylactic implantation of an implantable defibrillator (ICD) improve survival compared to conventional medical therapy in patients with a prior myocardial infarction and a left ventricular ejection fraction of ≤0.30?

Background

  • Disease Overview:
    • Patients with a history of myocardial infarction (MI) and significantly reduced left ventricular function (ejection fraction ≤0.30) are at increased risk for life-threatening ventricular arrhythmias and sudden cardiac death.
  • Prior Data:
    • 1996 & 1999 Studies: Demonstrated that ICD implantation improved survival in patients with coronary heart disease, reduced ventricular function, and inducible ventricular arrhythmias through invasive electrophysiological testing.
  • Current Standard of Care:
    • Prophylactic ICD implantation is recommended for selected high-risk post-MI patients to prevent sudden cardiac death.
  • Knowledge Gaps Addressed by the Study:
    • The necessity of invasive electrophysiological testing for risk stratification in determining ICD eligibility.
    • The effectiveness of ICD therapy without prior inducible arrhythmia testing.
  • Study Rationale:
    • To evaluate whether prophylactic ICD implantation improves survival in post-MI patients with severe left ventricular dysfunction in the absence of invasive arrhythmia risk stratification.

Methods Summary

  • Study Design: Randomized controlled trial (RCT)
  • Setting and Time Period: Conducted from July 11, 1997, to November 20, 2001, across 76 hospital centers (71 in the USA, 5 in Europe).
  • Population Characteristics: 1,232 patients with a history of MI ≥1 month and left ventricular ejection fraction ≤0.30.
  • Inclusion/Exclusion Criteria:
    • Inclusion: Adults >21 years with documented MI and severe left ventricular dysfunction.
    • Exclusion: Indication for ICD per FDA, NYHA class IV, recent coronary revascularization or MI, advanced cerebrovascular disease, high likelihood of death from non-cardiac conditions, unwillingness to consent.
  • Intervention Details: Implantation of transvenous defibrillator systems (Guidant) with standard implantation techniques.
  • Control/Comparison Group Details: Conventional medical therapy without ICD implantation.
  • Primary and Secondary Outcomes:
    • Primary Outcome: Death from any cause.
    • Secondary Outcomes: Hospitalization for heart failure, arrhythmia-related events, adverse events related to ICD therapy.
  • Basic Statistical Analysis Approach: Intention-to-treat analysis using Cox proportional-hazards regression, Kaplan-Meier survival curves, and hazard ratios with 95% confidence intervals.
  • Sample Size Calculations: Designed to detect a 38% reduction in two-year mortality with 95% power at a two-sided α=0.05.
  • Ethics and Funding Information: Approved by institutional review boards; conflict-of-interest guidelines adhered to; no limitations imposed by the sponsor on data analysis.

Results

  • Participant Flow and Demographics:
    • Total Participants: 1,232 (742 ICD, 490 conventional)
    • Follow-up Duration: Average of 20 months (range 6 days to 53 months)
    • Crossovers: 54 total (22 from conventional to ICD, 21 from ICD not implanted, 11 had ICD removed)
    • Follow-up Visit Attendance: 94% (conventional), 97% (ICD)
  • Primary Outcome Results:
    • Mortality Rates:
      • Conventional-Therapy: 19.8%
      • Defibrillator Group: 14.2%
    • Hazard Ratio: 0.69 (95% CI: 0.51–0.93; P=0.016), indicating a 31% reduction in the risk of death with ICD.
  • Secondary Outcome Results:
    • Heart Failure Hospitalizations:
      • Conventional-Therapy: 14.9%
      • Defibrillator Group: 19.9% (P=0.09)
  • Subgroup Analyses:
    • No significant differences in survival benefits across subgroups stratified by age, sex, ejection fraction, NYHA class, QRS interval, hypertension, diabetes, etc.
  • Adverse Events/Safety Data:
    • Serious Complications:
      • No deaths during implantation.
      • 1.8% lead problems, 0.7% nonfatal infections requiring surgical intervention.
      • Slight increase in heart failure hospitalizations in ICD group.
Outcome Intervention Group (ICD) Control Group Difference (95% CI) P-value
Primary Outcome (Death) 14.2% 19.8% -5.6% (-10.2 to -0.9%) 0.016
Heart Failure Hospitalization 19.9% 14.9% +5.0% (-0.2 to +10.2%) 0.09

Authors' Conclusions

  • Primary Conclusions: Prophylactic ICD implantation significantly improves survival in patients with a prior MI and a left ventricular ejection fraction of ≤0.30.
  • Clinical Implications Stated by Authors: ICD therapy should be considered a recommended treatment for the specified high-risk patient population.
  • Future Research Recommendations: Further studies to explore long-term outcomes, the impact of ICD therapy on different patient subgroups, and cost-effectiveness analyses.

Critical Analysis

A. Strengths

  • Methodological Strengths:
    • Large sample size (1,232 patients) enhancing the power and reliability of results.
    • Randomized controlled design minimizes selection bias and confounding factors.
    • Intention-to-treat analysis ensures preservation of randomization benefits.
  • Internal Validity Considerations:
    • Balanced baseline characteristics between groups.
    • High follow-up adherence rates (94-97%) reducing loss-to-follow-up bias.
  • External Validity Considerations:
    • Diverse study settings (71 US and 5 European centers) enhance generalizability.
    • Broad inclusion criteria without invasive arrhythmia testing make findings applicable to a wide patient population.

B. Limitations

  • Study Design Limitations or Biases:
    • Open-label design may introduce bias in management and reporting of outcomes.
  • Generalizability Issues:
    • Predominantly North American and European populations; applicability to other regions and ethnic groups may vary.
    • Exclusion of patients with certain comorbidities limits applicability to more complex clinical scenarios.
  • Statistical Limitations:
    • The follow-up period was relatively short (average 20 months); long-term benefits and risks remain uncertain.
  • Missing Data Handling or Loss to Follow-Up:
    • Minimal loss to follow-up (only three patients’ status unknown), but reasons for dropout could introduce bias if related to outcomes.

Literature Review

A. Positioning the Current Study in Existing Evidence

The Moss et al. (2002) study was a pivotal randomized controlled trial (RCT) that provided robust evidence supporting the prophylactic use of implantable cardioverter-defibrillators (ICDs) in patients with a history of myocardial infarction (MI) and severely reduced left ventricular ejection fraction (EF ≤0.30). This trial built upon earlier studies, such as the Multicenter Automatic Defibrillator Implantation Trial (MADIT) and the Survival and Ventricular Enlargement (SAVE) trial, which established the efficacy of ICDs and ACE inhibitors in improving survival among post-MI patients with left ventricular dysfunction.

Subsequent guidelines have incorporated the findings of Moss et al., recommending ICD implantation for primary prevention in similar high-risk populations. The American Heart Association (AHA) and American College of Cardiology (ACC) guidelines emphasize ICD therapy for patients with post-MI EF ≤35%, aligning with the Moss et al. study's inclusion criteria.

B. Comprehensive Synthesis of Findings

Supporting the Moss et al. findings, the BEST Guideline by Tamis-Holland et al. (2019) underscores the importance of comprehensive diagnostic evaluation in managing myocardial infarction, including the role of ICDs in appropriate patient subsets. This aligns with Moss et al. by emphasizing risk stratification based on EF to identify patients who would benefit most from ICD therapy.

The Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) by Pitt et al. (2003) complements Moss et al. by demonstrating the mortality benefits of aldosterone antagonists in reducing cardiovascular deaths and hospitalizations for heart failure, advocating for a multifaceted therapeutic approach alongside device therapy.

Further supporting Moss et al., the Multicenter Automatic Defibrillator Implantation Trial II (MADIT-II) explored the incidence and outcomes related to inappropriate ICD shocks. Daubert et al. (2008) found that inappropriate shocks occurred in 11.5% of patients and were associated with increased all-cause mortality, highlighting the need for optimal ICD programming to mitigate adverse outcomes.

Pietrasik et al. (2009) investigated the efficacy of ACE inhibitors and beta-blockers in reducing heart failure events among ICD-treated patients, finding that combination therapy significantly attenuated the increased risk of heart failure associated with ICD implantation. This underscores the importance of concurrent medical therapy to maximize the benefits of ICDs.

In Japanese populations, Kuga et al. (2014) conducted a subanalysis of the Japanese Coronary Artery Disease (JCAD) Study, which revealed that while prophylactic ICD use was less frequent and somewhat less effective compared to Western populations, it still offered survival benefits in Japanese patients with left ventricular dysfunction post-MI. This suggests potential geographical and population-based differences in ICD efficacy and utilization.

The Rostock Infarction Network (Drip & Ship) Registry elaborated by Paranskaya et al. (2011) indicated that despite an increase in ICD implantation rates post-MI, actual survival benefits were primarily associated with early ICD implantation following out-of-hospital cardiac arrest due to MI, reinforcing the importance of timely device therapy.

Zaman et al. (2014) demonstrated that patients with severely impaired LVEF but no inducible ventricular tachycardia had favorable long-term outcomes without ICD protection, suggesting that electrophysiological studies (EPS) could help identify patients who might safely avoid ICD implantation, thereby addressing the translation gap between study findings and clinical application.

In the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), Piccini et al. (2011) reported that ICD benefits were consistent irrespective of the time elapsed since MI, indicating that ICD therapy remains effective whether administered shortly after or many months post-MI. This finding broadens the clinical applicability of ICDs beyond early post-MI patients.

David et al. (2020) explored the prognosis of type 2 MI patients implanted with ICDs and found similar outcomes to type 1 MI patients, suggesting that ICD therapy could be beneficial across different MI etiologies within the severe CAD population. This challenges previous notions that ICD benefits are confined to type 1 MI patients and emphasizes the need for inclusive criteria in ICD recommendations.

C. Gaps and Future Directions

Despite the extensive evidence supporting ICD therapy in post-MI patients with reduced ejection fraction, several gaps persist:

  • Long-Term Outcomes: Most studies, including Moss et al., have limited follow-up durations. Longer-term studies are necessary to evaluate sustained benefits and late-onset adverse effects.
  • Optimal Patient Selection: While EF is a critical stratifier, additional biomarkers or imaging parameters could refine patient selection to maximize ICD benefits and minimize unnecessary implantations.
  • Cost-Effectiveness: With the rising costs of healthcare, comprehensive analyses assessing the cost-effectiveness of widespread ICD implantation are essential, especially in diverse healthcare settings.
  • Geographical and Population Variations: Studies like Kuga et al. highlight potential differences in ICD efficacy across populations. Future research should explore genetic, lifestyle, and healthcare system factors influencing ICD outcomes.
  • Managing Inappropriate Shocks: As identified by Daubert et al., inappropriate ICD shocks are a significant concern. Developing advanced device algorithms and personalized programming could reduce these events.
  • Integration with Modern Therapies: With advancements in heart failure therapies, such as newer pharmacological agents and cardiac resynchronization therapy, future studies should assess the additive or synergistic benefits of ICDs within these contemporary treatment paradigms.
  • Patient Quality of Life: Beyond mortality benefits, the impact of ICDs on patients’ quality of life, psychological well-being, and functional status warrants further investigation.

Clinical Application

  • The findings from Moss et al. (2002), corroborated by subsequent studies and guidelines, support the prophylactic implantation of ICDs in post-MI patients with an ejection fraction of ≤0.30 to significantly reduce all-cause mortality. This therapy is particularly applicable to patients with severe left ventricular dysfunction who are at high risk for ventricular arrhythmias.
  • Implementation should consider device programming to minimize inappropriate shocks and integrate optimal medical therapy with ACE inhibitors and beta-blockers to mitigate heart failure risks.
  • In diverse practice settings, especially in community and rural areas, ensuring access to ICD therapy and appropriate follow-up is crucial.
  • These results reinforce current guidelines, which advocate for individualized patient assessment to determine the suitability of ICD implantation, thereby enhancing evidence-based practice in cardiovascular care.

How To Use This Info In Practice

Practitioners should integrate ICD therapy into the management plan for post-MI patients with significantly reduced ejection fraction in accordance with current guidelines, ensuring optimal patient selection and concurrent medical therapy to maximize survival benefits and minimize adverse outcomes.