Heart failure (HF) is a growing problem. More than 20 million people worldwide are affected by HF, including more than 5 million in the United States alone.
HF affects 6 percent to 10 percent of people over the age of 65. Although the relative incidence is lower in women than in men, women constitute at least half of the cases of HF because of their longer life expectancy.
Hospitalization for acute decompensated heart failure (ADHF) is a powerful predictor of readmission and post-discharge death in patients with chronic HF, with mortality rates as high as 20 percent after discharge. The risk of adverse events after hospitalization may be increased for patients who do not have reductions in levels of brain natriuretic peptide (BNP) or N-terminal pro-BNP (NT-proBNP) between hospital admission and discharge.
TRUE-AHF was a Phase III, multicenter, randomized, double-blind, placebo-controlled clinical trial designed to evaluate the efficacy and safety of ularitide as an intravenous (IV) infusion in addition to conventional therapy in patients suffering from acute cardiac failure (ACF) — which is a sudden worsening of the signs and symptoms of HF. Symptoms include difficulty breathing, leg or feet swelling, and fatigue.
In this trial, 2,157 patients with ACF were assigned to receive a continuous IV infusion of either ularitide at a dose of 15 ng per kilogram of body weight per minute or matching placebo for 48 hours, in addition to accepted therapy. Death from cardiovascular causes occurred in 236 patients in the ularitide group and 225 patients in the placebo group (21.7 percent versus 21 percent).
The results showed that in patients with ACF, ularitide exerted favorable physiological effects (without affecting cardiac troponin levels), but short-term treatment did not affect a clinical composite endpoint or reduce long-term cardiovascular mortality.
Paul J. Hauptman, M.D., an SLUCare cardiologist specializing in HF and professor of internal medicine at Saint Louis University School of Medicine, has a background in clinical and outcomes research in HF, with more than 20 years as an investigator in multiple trials. He reviewed the two hypotheses of TRUE-AHF that a single infusion of ularitide would improve early clinical outcomes and that a rapid treatment approach to exacerbation of HF improves longer-term survival.
Hauptman concluded that ularitide has limited short-term effects that decrease after treatment is discontinued. According to Hauptman, it also appears that there is no mandate to establish rapid-response teams for patients who present with ADHF.
He suggests that the primary immediate objective of treatment should be the patient-centric goal of symptom relief so that mortality is once again relegated to a safety rather than an efficacy endpoint. Hauptman also asserts that exacerbations of chronic disease reflect the chronic disease, not the hospitalizations used to manage those exacerbations.
Researchers need a greater consensus on how to define the response to an intervention and to determine which patients are in greatest therapeutic need — for example, those with in-hospital worsening despite conventional therapy. Understanding the pathophysiology of HF and better treatments is an ongoing search.
