Implantable cardioverter-defibrillators for primary prevention of sudden cardiac death in CKD: a meta-analysis of patient-level data from 3 randomized trials

Abstract

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/1.73m2. 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.

Keywords: Implantable cardioverter-defibrillator (ICD); chronic kidney disease (CKD); heart failure; meta-analysis; reduced ejection fraction; sudden cardiac death.