New York Heart Association class and the survival benefit from primary prevention implantable cardioverter defibrillators: A pooled analysis of 4 randomized controlled trials

Abstract

Background: Primary prevention implantable cardioverter defibrillator (ICD) reduce all-cause mortality by reducing sudden cardiac death. There are conflicting data regarding whether patients with more advanced heart failure derive ICD benefit owing to the competing risk of nonsudden death.

Methods: We performed a patient-level meta-analysis of New York Heart Association (NYHA) class II/III heart failure patients (left ventricular ejection fraction ≤35%) from 4 primary prevention ICD trials (MADIT-I, MADIT-II, DEFINITE, SCD-HeFT). Bayesian-Weibull survival regression models were used to assess the impact of NYHA class on the relationship between ICD use and mortality.

Results: Of the 2,763 patients who met study criteria, 68% (n=1,867) were NYHA II and 52% (n=1,435) were randomized to an ICD. In a multivariable model including all study patients, the ICD reduced mortality (hazard ratio [HR] 0.65, 95% posterior credibility interval [PCI]) 0.40-0.99). The interaction between NYHA class and the ICD on mortality was significant (posterior probability of no interaction=.036). In models including an interaction term for the NYHA class and ICD, the ICD reduced mortality among NYHA class II patients (HR 0.55, PCI 0.35-0.85), and the point estimate suggested reduced mortality in NYHA class III patients (HR 0.76, PCI 0.48-1.24), although this was not statistically significant.

Conclusions: Primary prevention ICDs reduce mortality in NYHA class II patients and trend toward reducing mortality in the heterogeneous group of NYHA class III patients. Improved risk stratification tools are required to guide patient selection and shared decision making among NYHA class III primary prevention ICD candidates.

Figure 1

Consort diagram depicting derivation of the study population.

Figure 2

Kaplan-Meier curves depicting differences in survival among patients randomized to ICD versus no ICD among (A) NYHA class II and (B) NYHA class III patients. The differences in the risk of death by treatment group were assessed using unadjusted Cox proportional hazards models.

Figure 3

Cumulative incidence functions depicting sudden versus nonsudden death among patients randomized to ICD versus no ICD when stratified by NYHA class. NYHA II patients are compared in the left pane; NYHA III patients are compared in the right pane.