Worsening Renal Function and Outcome in Heart Failure Patients With Preserved Ejection Fraction and the Impact of Angiotensin Receptor Blocker Treatment

Study Questions:

What is the relationship between worsening renal failure (WRF) and outcomes in heart failure patients with preserved ejection fraction (HFpEF), and the interaction with renin-angiotensin-aldosterone system (RAAS) blockade?


The study cohort was comprised of 3,595 patients included in the I-PRESERVE (Irbesartan in Heart Failure with Preserved Ejection Fraction) trial. The study investigators evaluated change in estimated glomerular filtration rate (eGFR) and development of WRF after initiation of irbesartan or placebo. They also examined the association between WRF and the first occurrence of cardiovascular death or HF hospitalization (primary outcome in this analysis) and the interaction with randomized treatment.


The study investigators found that eGFR decreased early with irbesartan treatment and remained significantly lower than in the placebo group. WRF developed in 6.4% (229) of the patients and occurred more frequently with irbesartan treatment (8% vs. 4%). Overall, WRF was associated with an increased risk of the primary outcome (adjusted hazard ratio [HR], 1.43; 95% confidence interval [CI], 1.10-1.85; p = 0.008). Although, the risk related to WRF was greater in the irbesartan group (HR, 1.66; 95% CI, 1.21-2.28; p = 0.002) than with placebo (HR, 1.09; 95% CI, 0.66-1.79; p = 0.73), the interaction was significant in an adjusted analysis.


The authors concluded that the incidence of WRF in HFpEF is similar to that previously reported in HF with reduced EF (HFrEF), but more frequent with irbesartan than with placebo. WRF after initiation of irbesartan treatment in HFpEF was with RAAS blockade in HFrEF.


This is an important study, first, because it confirms what most astute clinicians have suspected (i.e., diastolic HF is often accompanied by significant underlying renal dysfunction). Second, it suggests that therapies being evaluated for diastolic HF must also target underlying renal dysfunction in order to improve outcomes. Third, this study now raises the question on what are the predictors of worsening renal function with RAAS blockade in HF.

Clinical Topics: Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: Angiotensin Receptor Antagonists, Biphenyl Compounds, Heart Failure, Glomerular Filtration Rate, Confidence Intervals, Tetrazoles

< Back to Listings