Marcello Disertori1, Michela Masè2, Marta Rigoni3, Giandomenico Nollo4, Flavia Ravelli5. 1. Healthcare Research and Innovation Program, PAT-FBK, Trento, Italy; Department of Cardiology, Santa Chiara Hospital, Trento, Italy. Electronic address: disertorim@gmail.com. 2. Healthcare Research and Innovation Program, PAT-FBK, Trento, Italy; Department of Physics, University of Trento, Povo, Trento, Italy. 3. Healthcare Research and Innovation Program, PAT-FBK, Trento, Italy. 4. Healthcare Research and Innovation Program, PAT-FBK, Trento, Italy; Department of Industrial Engineering, University of Trento, Povo, Trento, Italy. 5. Department of Physics, University of Trento, Povo, Trento, Italy.
Abstract
BACKGROUND: The risk of sudden cardiac death in patients with heart failure has declined over time thanks to the sequential introduction of new treatments. However, current guidelines recommendations for implantable cardioverter-defibrillator (ICD) are based on randomized controlled trials (RCTs) carried out in the past three decades and their meta-analyses. To highlight potential changes over time in ICD clinical benefit in primary prevention of sudden cardiac death, we analyzed the temporal trends of RCT risk of mortality outcomes in this time frame. METHODS: By searching MEDLINE and the Cochrane Library electronic databases we identified seven RCTs (6095 patients enrolled between 1990 and 2014) on ICD versus contemporary standard medical therapy for sudden cardiac death prevention, in patients with chronic heart failure of ischemic and non-ischemic origin and reduced ejection fraction. Linear regression analysis was applied to identify the association between RCT mortality outcomes and time. RESULTS: Ordered according to the start of randomization, the trials showed a statistically significant (p=0.03) progressive decline in the baseline annualized event rate of sudden cardiac death in RCT control arms, and a significant (p=0.04) increase in the number of patients unresponsive to ICD treatment (i.e. patients experiencing sudden cardiac death in ICD arms). These two factors synergistically contributed to a significant (p<0.01) and progressive reduction in the clinical benefit of ICD, assessed by the number needed to treat for total mortality at 3 years. CONCLUSIONS: The clinical benefit of ICD, implanted according to the current guidelines, has significantly and progressively declined over time due to the reduction in sudden cardiac death risk and to the increase of ICD unresponsive patients.
BACKGROUND: The risk of sudden cardiac death in patients with heart failure has declined over time thanks to the sequential introduction of new treatments. However, current guidelines recommendations for implantable cardioverter-defibrillator (ICD) are based on randomized controlled trials (RCTs) carried out in the past three decades and their meta-analyses. To highlight potential changes over time in ICD clinical benefit in primary prevention of sudden cardiac death, we analyzed the temporal trends of RCT risk of mortality outcomes in this time frame. METHODS: By searching MEDLINE and the Cochrane Library electronic databases we identified seven RCTs (6095 patients enrolled between 1990 and 2014) on ICD versus contemporary standard medical therapy for sudden cardiac death prevention, in patients with chronic heart failure of ischemic and non-ischemic origin and reduced ejection fraction. Linear regression analysis was applied to identify the association between RCT mortality outcomes and time. RESULTS: Ordered according to the start of randomization, the trials showed a statistically significant (p=0.03) progressive decline in the baseline annualized event rate of sudden cardiac death in RCT control arms, and a significant (p=0.04) increase in the number of patients unresponsive to ICD treatment (i.e. patients experiencing sudden cardiac death in ICD arms). These two factors synergistically contributed to a significant (p<0.01) and progressive reduction in the clinical benefit of ICD, assessed by the number needed to treat for total mortality at 3 years. CONCLUSIONS: The clinical benefit of ICD, implanted according to the current guidelines, has significantly and progressively declined over time due to the reduction in sudden cardiac death risk and to the increase of ICD unresponsive patients.