Quarterly Focus Issue: Heart Failure
Clinical Research
Quantitative Evaluation of Drug or Device Effects on Ventricular Remodeling as Predictors of Therapeutic Effects on Mortality in Patients With Heart Failure and Reduced Ejection Fraction: A Meta-Analytic Approach

https://doi.org/10.1016/j.jacc.2010.05.011Get rights and content
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Objectives

The purpose of this study was to quantitatively assess the relationship between therapy-induced changes in left ventricular (LV) remodeling and longer-term outcomes in patients with left ventricular dysfunction (LVD).

Background

Whether therapy-induced changes in left ventricular ejection fraction (LVEF), end-diastolic volume (EDV), and end-systolic volume (ESV) are predictors of mortality in patients with LVD is not established.

Methods

Searches for randomized controlled trials (RCTs) were conducted to identify drug or device therapies for which an effect on mortality in patients with LVD was studied in at least 1 RCT of ≥500 patients (mortality trials). Then, all RCTs involving those therapies were identified in patients with LVD that described changes in LVEF and/or volumes over time (remodeling trials). We examined whether the magnitude of remodeling effects is associated with the odds ratios for death across all therapies or associated with whether the odds ratio for mortality was favorable, neutral, or adverse (i.e., statistically significantly decreased, nonsignificant, or statistically significantly increased odds for mortality, respectively).

Results

Included were 30 mortality trials of 25 drug/device therapies (n = 69,766 patients; median follow-up 17 months) and 88 remodeling trials of the same therapies (n = 19,921 patients; median follow-up 6 months). The odds ratio for death in the mortality trials was correlated with drug/device effects on LVEF (r = −0.51, p < 0.001), EDV (r = 0.44, p = 0.002), and ESV (r = 0.48, p = 0.002). In (ordinal) logistic regressions, the odds for neutral or favorable effects in the mortality RCTs increased with mean increases in LVEF and with mean decreases in EDV and ESV in the remodeling trials.

Conclusions

In patients with LVD, short-term trial-level therapeutic effects of a drug or device on LV remodeling are associated with longer-term trial-level effects on mortality.

Key Words

heart failure
remodeling
clinical trials

Abbreviations and Acronyms

AUC
area under the curve
CI
confidence interval
EDV
end-diastolic volume
ESV
end-systolic volume
HF
heart failure
IQR
interquartile range
LVD
left ventricular dysfunction
LVEF
left ventricular ejection fraction
NYHA
New York Heart Association
OR
odds ratio
RCT
randomized controlled trial
ROC
receiver-operating characteristic

Cited by (0)

This article was partially funded by the grant NIH/NCRR UL1RR025752, Tufts Clinical and Translational Science Institute. Dr. Konstam is a consultant for Boehringer-Ingelheim, Trevena, Johnson & Johnson, Cardioxyl, Merck, and Forest. Dr. Udelson is a consultant for Cytori, Angioblast, and Medtronic.