Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death in CKD: A Meta-analysis of Patient-Level Data From 3 Randomized Trials
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Figure 1
Study selection and patient inclusion within selected studies. Abbreviations: AVID, Antiarrhythmics Versus Implantable Defibrillators; CABG-PATCH, Coronary Artery Bypass Graft Patch; CASH, Cardiac Arrest Study Hamburg; CHF, congestive heart failure; DEFINITE, Defibrillators in Non-ischemic Cardiomyopathy Treatment Evaluation; DINAMIT, Defibrillator in Acute Myocardial Infarction Trial; ICD, implantable cardioverter-defibrillator; LVEF, left ventricular ejection fraction; MADIT, Multicenter Automatic Defibrillator Implantation Trial; MUSTT, Multicenter Unsustained Tachycardia Trial; NYHA, New York Heart Association; RCT, randomized controlled trial; SCD-HeFT, Sudden Cardiac Death in Heart Failure Trial.
Figure 2
Kaplan-Meier survival curves in implantable cardioverter-defibrillator (ICD) recipients versus nonrecipients according to estimated glomerular filtration rate (eGFR). Unadjusted hazard ratios for the mortality benefit of ICDs are 0.92 and 0.53 (95% confidence intervals, 0.74-1.14 and 0.42-0.67) for eGFRs < 60 and ≥60 mL/min/1.73 m2.
Figure 3
Proportion (%) of study participants with adverse outcomes by estimated glomerular filtration rate (eGFR) group. Abbreviations: CKD, chronic kidney disease; Comp, complications; Cont, control arm; eGFR, estimated glomerular filtration rate; ICD, implantable cardioverter-defibrillator; Rehosp, rehospitalizations.
Figure 4
Bayesian Weibull covariate-adjusted hazard ratio for mortality benefit of an implantable cardioverter-defibrillator (ICD) as a function of baseline estimated glomerular filtration rate (eGFR). Shaded areas reflect 95% point-wise posterior credible intervals.
Figure 5
Forest plots of covariate-adjusted hazard rations (HRs) and 95% posterior credible intervals (PCIs) for (A) all-cause mortality and (B) rehospitalizations by clinical trial and estimated glomerular filtration rate (eGFR) group, with x-axis displayed in the log-scale. Abbreviations: ICD, implantable cardioverter-defibrillator; MADIT, Multicenter Automatic Defibrillator Implantation Trial; OR, odds ratio; SCD-HeFT, Sudden Cardiac Death in Heart Failure Trial.
Background
The benefit of a primary prevention implantable cardioverter-defibrillator (ICD) among patients with chronic kidney disease is uncertain.
Study Design
Meta-analysis of patient-level data from randomized controlled trials.
Setting & Population
Patients with symptomatic heart failure and left ventricular ejection fraction < 35%.
Selection Criteria for Studies
From 7 available randomized controlled studies with patient-level data, we selected studies with available data for important covariates. Studies without patient-level data for baseline estimated glomerular filtration rate (eGFR) were excluded.
Intervention
Primary prevention ICD versus usual care effect modification by eGFR.
Outcomes
Mortality, rehospitalizations, and effect modification by eGFR.
Results
We included data from the Multicenter Automatic Defibrillator Implantation Trial I (MADIT-I), MADIT-II, and the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). 2,867 patients were included; 36.3% had eGFR < 60 mL/min/1.73 m2. Kaplan-Meier estimate of the probability of death during follow-up was 43.3% for 1,334 patients receiving usual care and 35.8% for 1,533 ICD recipients. After adjustment for baseline differences, there was evidence that the survival benefit of ICDs in comparison to usual care depends on eGFR (posterior probability for null interaction P < 0.001). The ICD was associated with survival benefit for patients with eGFR≥60 mL/min/1.73 m2 (adjusted HR, 0.49; 95% posterior credible interval, 0.24-0.95), but not for patients with eGFR < 60 mL/min/1.73 m2 (adjusted HR, 0.80; 95% posterior credible interval, 0.40-1.53). eGFR did not modify the association between the ICD and rehospitalizations.
Limitations
Few patients with eGFR < 30 mL/min/1.73 m2 were available. Differences in trial-to-trial measurement techniques may lead to residual confounding.
Conclusions
Reductions in baseline eGFR decrease the survival benefit associated with the ICD. These findings should be confirmed by additional studies specifically targeting patients with varying eGFRs.
Index Words:
Implantable cardioverter-defibrillator (ICD), sudden cardiac death, chronic kidney disease (CKD), reduced ejection fraction, heart failure, meta-analysisTo access this article, please choose from the options below
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