New Inhibitor for Heart Failure Treatment Avoids Anemia

Anemia is a common complication associated with worse outcome in patients with heart failure with reduced ejection fraction. Renin-angiotensin system (RAS) blockers, such as angiotensin-converting enzyme inhibitors, lower hemoglobin and may induce anemia.

In the PARADIGM-HF trial, published in JACC Heart Failure, James Curtain and colleagues explored whether sacubitril/valsartan, the first approved angiotensin receptor neprilysin inhibitor (ARNI) therapy, could avoid this effect of renin-angiotensin system blockers and improve treatment outcomes in patients with heart failure with preserved ejection fraction, with or without existing anemia.

According to the study, sacubitril and valsartan improved mortality and hospitalization outcomes compared with enalapril in patients with heart failure with preserved ejection fraction, regardless of concurrent anemia. Sacubitril and valsartan also reportedly led to milder decreases in hemoglobin and fewer incidences of new anemia.

First ARNI Therapy Improves Anemia in Heart Failure

The primary end points were clinical outcomes per anemia status, changes in hemoglobin, and overall anemia incidence. Anemia was defined as hemoglobin <120 g/L in women and <130 g/L in men.

Researchers analyzed 8239 patients from the PARADIGM-HF trial, of whom 1677 (20.4%) had anemia. Authors noted patients with anemia had more severe heart failure, poorer kidney function, increased neurohormonal derangement, and worse clinical outcomes.

Compared with enalapril, investigators stated sacubitril/valsartan decreased the risk of cardiovascular mortality or hospitalization for heart failure in both patients with (hazard ratio [HR], 0.84; 95% CI, 0.71-1.00) or without anemia (HR, 0.78; 95% CI, 0.71-0.87; P=.478).

At month 12 compared with baseline, patients treated with sacubitril/valsartan had a mean hemoglobin decrease of 1.5 g/L (95% CI, 1.2-1.7) compared with 2.3 g/L (95% CI, 2.0-2.6) in patients treated with enalapril (mean difference 0.8 g/L; 95% CI, 0.5-1.2; P<.001). Likewise, the incidence of anemia at 12 months was 321 (11.4%) out of 2806 participants in the sacubitril/valsartan group versus 440 (25.6%) out of 2824 in the enalapril group (odds ratio, 0.70; 95% CI, 0.60-0.81; P<.001).

The investigators noted their results were similar to findings from the PARAGON-HF study on patients with heart failure with preserved ejection fraction treated with sacubitril/valsartan versus valsartan alone.

Further studies examining neprilysin inhibitors “would develop a greater understanding of the mechanisms by which sacubitril/valsartan decreases the development of anemia compared with RAS blockers,” Curtain and colleagues closed.

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