Mortality reduction with implanted defibrillator for primary prevention of sudden death after Myocardial Infarction: temporal trends in the PROFID study
Alireza Sepehri ShamlooToshinori ChibaJG TijssenTill AlthoffSerge BovédaFrieder BraunschweigChristian de ChillouJonas FaxénTim FriedeLaura FusiniChris P GaleRobert HättaschFelix HohendannerJuhani JunttilaThomas KaasZoher KapaceeAntti M. KiviniemiValentina KutyifaChristophe LeclercqRadosław LenarczykDr Francisco LeyvaMichael MængÉloi MarijonJosé L MerinoLluís MontJens Cosedis NielsenKevin Kris Warnakula OlesenGianluca PontoneHelmut PürerfellnerGeorg SchmidtPeter J. SchwartzChristian SticherlingMahmoud SuleimanHanno L. TanJacob Tfelt‐HansenHölger ThieleVerena TschollTom E. VerstraelenArthur A.M. WildeKatherine WuMarkus ZabelGerhard HindricksNikolaos Dagres
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Key result
Primary prevention ICDs show no significant survival benefit post-MI in the modern era.
- HR 0.89
- 95% CI 0.73-1.07
- P=0.221
- n=32,214
Why the study?
Randomized trials in the early 2000s established survival benefit of primary prevention ICD therapy after myocardial infarction, but management of myocardial infarction and heart failure has evolved substantially since then.
Does primary prevention ICD implantation reduce all-cause mortality in post-myocardial infarction patients with LVEF ≤35%?
Key Points
- To investigate whether the estimated association between primary prevention implantable cardioverter-defibrillator (ICD) implantation and mortality reduction has changed over time in post-myocardial infarction patients with reduced left ventricular ejection fraction (LVEF).
- Analyzed individual participant data from 32,214 patients with LVEF ≤35% after myocardial infarction in the PROFID pooled cohort, comprising 7,477 ICD patients and 24,737 non-ICD patients.
- Evaluated all-cause mortality across three prespecified time periods (1995–2004, 2005–2014, and 2015–2020) using propensity score overlap weighting and weighted Cox proportional hazards models.
- Across a mean follow-up of 43.7 months and 12,097 all-cause deaths, the association between ICD implantation and mortality changed significantly over time (P for interaction <0.001).
- In weighted time period-specific analyses, the hazard ratio for ICD versus non-ICD patients was 0.54 (95% CI 0.47–0.62; P<0.001) in 1995–2004, 0.67 (95% CI 0.62–0.72; P<0.001) in 2005–2014, and 0.89 (95% CI 0.73–1.07; P=0.221) in 2015–2020.
- The interaction estimate comparing 1995–2004 with 2015–2020 was 0.61 (95% CI 0.48–0.78; P<0.001), showing progressive attenuation of benefit with negligible separation of weighted cumulative mortality curves in the most recent period.
Study Design
Type
Cohort (n=32,214)
Multicenter
Yes
Structured PICO
Does primary prevention ICD implantation reduce all-cause mortality in post-myocardial infarction patients with LVEF ≤35%?
P
Population
32,214 adult patients with an LVEF ≤35% after a myocardial infarction were followed for a mean of 43.7 months to assess temporal changes in the survival benefit of primary prevention ICD implantation.
E
Exposure
Primary prevention implantable cardioverter-defibrillator (ICD)
C
Comparator
No ICD within three months after the index myocardial infarction (non-ICD patients)
O
Outcome
All-cause mortalityhard clinical
Main Result
Hazard Ratio: 0.89 (95% CI 0.73–1.07)
p-value: p=0.221
Limitations
- ICD implantation was not randomly assigned, meaning residual unmeasured confounding may persist despite propensity score weighting.
- Calendar year at time zero does not fully capture changes in treatment exposure during follow-up and reflects the aggregate clinical environment rather than a single therapeutic change.
- Differences in contributing dataset composition across time periods due to varied study designs and regions.
- Evolving patient selection criteria and competing non-arrhythmic mortality risks over time may have influenced the observed attenuation in mortality differences.
- Calendar year at time zero does not fully capture changes in treatment exposure during follow-up.
- Calendar year may partly reflect differences in cohort composition due to different contributing studies and registries.
Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
“Our findings do not mean that ICD use in myocardial infarction patients with severely reduced pump function is generally no longer beneficial. Rather, they show that the current strategy of prophylactically implanting a defibrillator in these patients cannot be a one-size-fits-all solution. Each case must be considered individually.”
“To determine precisely which myocardial infarction patients truly benefit from a defibrillator, and for which patients medication alone is sufficient, we need randomised data. This is exactly the question we are currently investigating in a clinical trial. The results could significantly change the treatment of patients following a myocardial infarction in future.”
Implication
The survival benefit of primary prevention ICDs in post-myocardial infarction patients with reduced LVEF has significantly attenuated over the last two decades, questioning the current approach of routine prophylactic implantation based predominantly on LVEF.
Abstract
BACKGROUND AND AIM: Randomized trials conducted in the early 2000s established the survival benefit of primary prevention implantable cardioverter-defibrillator (ICD) therapy in patients with reduced left ventricular ejection fraction (LVEF) after myocardial infarction. However, management of myocardial infarction and heart failure has substantially evolved since that time. We investigated whether the estimated association between primary prevention ICD implantation in post-myocardial infarction patients with reduced LVEF and mortality reduction has changed over time. METHODS: We analyzed individual participant data from 32,214 patients with LVEF ≤35% after myocardial infarction included in the PROFID pooled cohort, comprising 7,477 patients carrying a primary prevention ICD (ICD patients) and 24,737 patients without an ICD (non-ICD patients). The primary endpoint was all-cause mortality. Propensity scores were estimated using multivariable logistic regression including age, sex, LVEF, renal function, and diabetes, and overlap weighting was applied to balance treatment groups. Time period-specific analyses were performed across three prespecified time periods defined by inclusion year: 1995-2004, 2005-2014, and 2015-2020. Weighted cumulative mortality curves were generated for each time period. Temporal changes in the estimated association between ICD implantation and mortality reduction were assessed using a weighted Cox proportional hazards model. RESULTS: A total of 12,097 deaths occurred during a mean follow-up of 43.7 months. The estimated association between ICD implantation and mortality changed significantly across time (P for interaction <0.001). In weighted time period-specific analyses, the estimated mortality reduction associated with ICD implantation progressively decreased over more recent periods. The hazard ratio for ICD versus non-ICD patients was 0.54 (95% CI 0.47-0.62; P<0.001) in 1995-2004, 0.67 (95% CI 0.62-0.72; P<0.001) in 2005-2014, and 0.89 (95% CI 0.73-1.07; P=0.221) in 2015-2020, with negligible separation of the weighted cumulative mortality curves in the most recent time period. CONCLUSIONS: In this analysis including a large cohort of post-myocardial infarction patients with reduced LVEF, the estimated mortality reduction associated with primary prevention ICD implantation progressively decreased over time.
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Cite This Study
Shamloo et al. (2026) conducted a cohort in Post-myocardial infarction with reduced left ventricular ejection fraction (LVEF ≤35%) (n=32,214). Primary prevention implantable cardioverter-defibrillator (ICD) implantation vs. No ICD implantation was evaluated on All-cause mortality (2015-2020 time period) (HR 0.89, 95% CI 0.73-1.07, p=0.221). The estimated mortality reduction associated with primary prevention ICD implantation in post-myocardial infarction patients progressively decreased over time, reaching a statistically non-significant HR of 0.89 in the 2015-2020 period.
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