This article is more than 5 years old. Information may no longer be current.
Worsening renal function after irbesartan linked to poor outcomes in HFpEF
Click Here to Manage Email Alerts
The incidence of worsening renal function after treatment with the angiotensin receptor blocker irbesartan was associated with increased risk for poor clinical outcomes among patients with HF with preserved ejection fraction, researchers reported in the Journal of the American College of Cardiology.
This finding is in contrast to that observed in patients with HF with reduced ejection fraction, in whom there is a similar incidence of worsening renal function but fewer poor outcomes, according to the researchers.
Kevin Damman, MD, PhD, and colleagues evaluated changes in estimated glomerular filtration rate (eGFR) and the incidence of worsening renal function at 8 weeks among 3,595 patients enrolled in the I-PRESERVE study who received irbesartan or placebo. The patients were aged 60 years and older and had symptoms of HF and preserved ejection fraction (HFpEF).
The primary outcome of this analysis was the incidence of CV-related death or HF hospitalization. Secondary outcomes included all-cause mortality and HF hospitalization.
“Overall, the occurrence of [worsening renal function] was associated with worse clinical outcomes compared with no [worsening function],” the researchers wrote. “This association seemed to be stronger in patients receiving irbesartan compared with placebo, contrasting strikingly with studies of [renin-angiotensin-aldosterone system] inhibition in [HF with reduced ejection fraction].”
Damman and colleagues noted that results from this study differ from earlier observations because they investigated a previously unstudied patient population with chronic HFpEF.
Patients who received irbesartan experienced an early decrease in eGFR and maintained a significantly lower eGFR than patients who received placebo (mean decrease, –7.2 ± 23 mL/min/1.73 m2 vs. –3.4 ± 23 mL/min/1.73 m2; P<.001). After 8 weeks, 6.4% of patients overall developed worsening renal function, including 8.4% of irbesartan recipients and 4.3% of the placebo group (OR=2.07; 95% CI, 1.56-2.75).
During a mean follow-up of 46 months, the primary endpoint occurred in 895 patients overall, including 37% of patients with worsening renal function and 24% of those without worsening renal function. The development of worsening renal function was significantly associated with incidence of the primary outcome (adjusted HR=1.43; 95% CI, 1.1-1.85), and this risk was more pronounced among irbesartan recipients (HR=1.66; 95% CI, 1.21-2.28 vs. HR=1.09; 95% CI, 0.66-1.79). However, adjusted analysis did not yield a significant interaction between treatment and worsening renal function.
In a related editorial, Marco Metra, MD, and Carlo Lombardi, MD, of the Cardiology Institute at University and Civil Hospital of Brescia, Italy, commended the researchers for their study, “which adds another piece to the puzzle of the complex relationships among the renin-angiotensin system, renal function and cardiac function,” they wrote. “Although we are still lacking data showing efficacy of any treatment, at least we are now aware of a new potential danger associated with a treatment widely shown as life-saving in other conditions.”
For more information:
Damman K. J Am Coll Cardiol. 2014;doi:10.1016/j.jacc.2014.01.087.
Metra M. J Am Coll Cardiol. 2014;doi:10.1016/j.jacc.2014.04.080.
Disclosure: See the full study for a list of the researchers’ relevant financial disclosures. Metra reports receiving consulting fees from Bayer, Novartis and Servier. Lombardi reports no relevant financial disclosures.