Tucson, AZ—Despite strong evidence for effectiveness and clear guidelines calling for their use for HFrEF patients, prescribing of ARNIs in the U.S. remains suboptimal, according to a new study.

"Factors responsible for under prescription are not completely understood," suggested University of Arizona Tucson—led researchers. "Economic limitations may play a disproportionate role in reduced access for some patients."

The study team conducted an analysis of the "Get With The Guidelines-Heart Failure" registry with supplemented data from the Distressed Community Index. The goal was to investigate clinical and socioeconomic factors associated with ARNI prescribing at hospital discharge. The results were published in Circulation Heart Failure.

The analysis included 136,144 patients, with 12.6% prescribed an ARNI at discharge. The researchers reported that the most important determinants of ARNI prescribing were ARNI use while inpatient (odds ratio [OR], 72 [95% CI, 58-89]; P < 001) and taking an ARNI before hospitalization (OR, 9 [95% CI, 7-13]; P <.001).

On the other hand, having an angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blocker (ARB)/ARNI contraindication was associated with lower likelihood of ARNI prescription at discharge (OR, 0.11 [95% CI, 0.10-0.12]; P <.001).

The study found that socioeconomic factors associated with lower likelihood of ARNI prescription included having no insurance (OR, 0.60 [95% CI, 0.50-0.72]; P <.001) and living in a ZIP Code identified as distressed (OR, 0.81 [95% CI, 0.70-0.93]; P = .010).

"The rate of ARNI prescription is increasing with time (OR, 2 [95% CI, 1.8-2.3]; P <.001 for patients discharged in 2020 as opposed to 2017), but the disparity in prescription rates between distressed and prosperous communities appears to be increasing," the authors wrote.

The researchers concluded, "Multiple medical and socioeconomic factors contribute to low rates of ARNI prescription at hospital discharge. Potential targets for improving ARNI prescription rates include initiating ARNIs during hospitalization and aggressively addressing patients' access barriers with the support of inpatient social services and pharmacists."

Background information in the article noted that more than 6 million people in the U.S. have a heart failure (HF) diagnosis, with approximately one-half of them having reduced ejection fraction, defined as a left ventricular ejection fraction <40%.

The authors advised that large, randomized clinical trials of patients with HFrEF have found a 20% reduction in cardiovascular death and hospitalizations with ARNIs compared with 10 mg twice daily of enalapril—an active ACE-inhibitor comparator. They noted that some models predicted more than 30,000 deaths per year could be prevented by switching patients from an ACE inhibitor or ARB to an ARNI. "Accordingly, HF guidelines now recommend ARNI as first line therapy for HF with reduced ejection fraction," they wrote.

All of that notwithstanding, prescription rates for ARNIs have lagged, ranging from 4% to 26% in studies performed in the past 5 years. One issue is that the therapy is not covered by all insurance vendors, and out-of-pocket costs to patients can exceed $680 per month without insurance, the study pointed out.

"Contraindications for ARNIs are similar to ACE inhibitors and ARBs, and studies have showed similar rates of side effects and complications, so it is unlikely the low prescription rates are due primarily to medical reasons," according to authors of the study, who emphasized the importance of understanding why the drugs are underprescribed and are developing strategies to remedy that.

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