Maximizing survival benefit with primary prevention implantable cardioverter-defibrillator therapy in a heart failure population

Abstract

Background: Although implantable cardioverter-defibrillator (ICD) therapy reduces mortality in moderately symptomatic heart failure patients with an ejection fraction <or=35%, many such patients do not require ICD shocks over long-term follow-up.

Methods and results: Using a modification of a previously validated risk prediction model based on routine clinical variables, we examined the relationship between baseline predicted mortality risk and the relative and absolute survival benefits of ICD treatment in the primary prevention Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT). In the placebo arm, predicted 4-year mortality grouped into 5 equal-sized risk groups varied from 12% to 50% (c statistic=0.71), whereas the proportion of SCD in those same risk groups decreased from 52% to 24% of all deaths. ICD treatment decreased relative risk of SCD by 88% in the lowest-risk group versus 24% in the highest-risk group (P=0.009 for interaction) and decreased relative risk of total mortality by 54% in the lowest-risk group versus no benefit (2%) in the highest-risk group (P=0.014 for interaction). Absolute 4-year mortality reductions were 6.6%, 8.8%, 10.6%, 14.0%, and -4.9% across risk quintiles. In highest-risk patients (predicted annual mortality >20%), no benefit of ICD treatment was seen. Projected over each patient's predicted lifespan, ICD treatment added 6.3, 4.1, 3.0, 1.9, and 0.2 additional years of life in the lowest- to highest-risk groups, respectively.

Conclusions: A clinical risk prediction model identified subsets of moderately symptomatic heart failure patients in SCD-HeFT in whom single-lead ICD therapy was of no benefit and other subsets in which benefit was substantial.

Trial registration: ClinicalTrials.gov NCT00000609.

Figure 1

SHFM-Predicted vs. Observed (Kaplan-Meier) Survival among Patients in the SCD-HeFT Placebo Arm The predicted survival by the Seattle Heart Failure Model and the observed (Kaplan-Meier) survival is shown for quintiles of the placebo group at 1- and 4-years. The predicted and observed mortality at 4 years was 71%. The diagonal line is the line of identity.

Figure 2

The ICD hazard ratio varied with the Seattle Heart Failure Model predicted mortality. The relative risk of all-cause mortality and sudden cardiac death due to ICD therapy varied according to SHFM-predicted risk. The estimated hazard ratios of ICD treatment across the SHFM predicted annual mortality generated from a Cox proportional hazards model including a SHFM*ICD multiplicative interaction term.are plotted for total mortality (blue) and sudden cardiac death (red) for quintiles of predicted risk. The points shown in the plot are the hazard ratios generated separately for each quintile of SHFM predicted risk.

Figure 3

Kaplan-Meier Survival curves for Quintiles of SHFM predicted survival. The Kaplan-Meier survival curves for SHFM predicted quintiles are shown for the placebo and the ICD groups. The hazard ratio and p values using a linear interaction model for SHFM*ICD is shown for each quintile.

Figure 3

Kaplan-Meier Survival curves for Quintiles of SHFM predicted survival. The Kaplan-Meier survival curves for SHFM predicted quintiles are shown for the placebo and the ICD groups. The hazard ratio and p values using a linear interaction model for SHFM*ICD is shown for each quintile.

Figure 3

Kaplan-Meier Survival curves for Quintiles of SHFM predicted survival. The Kaplan-Meier survival curves for SHFM predicted quintiles are shown for the placebo and the ICD groups. The hazard ratio and p values using a linear interaction model for SHFM*ICD is shown for each quintile.

Figure 4

Kaplan-Meier 4 year mortality for placebo and ICD groups. The observed (Kaplan-Meier) mortality at 4 years of the placebo and ICD groups are shown above for each SHFM estimated quintile of risk. The absolute reduction in mortality (shown above each quintile) ranged from ~7 to 14% in quintiles 1 to 4 with no benefit in quintile 5.

Figure 5

The projected lifespan for each quintile of the placebo and ICD group Figure 5a. The projected total lifespan estimate (Gompertz method) for each patient within each quintile was averaged for all placebo and ICD patients within the quintile according to SHFM-predicted risk. Figure 5b shows the difference in total lifespan between the placebo and ICD group averaged over a lifetime. In quintile 1, the average patient will live ~6 years longer but will require ~3 ICDs over the 22 year projected lifespan. Assuming a 7-year ICD battery life, 2.0 life-years were saved per ICD for patients with an average SHFM-predicted 2.5% annual mortality but decreased to 0.2 life-years for quintile 5.