OBJECTIVES: Patients with worsening heart failure (WHF) have increased risk of future WHF events and death. In clinical trials, guideline directed medical therapy (GDMT) reduces this risk, but few patients in the real-world receive optimal GDMT, rendering its effectiveness unclear.

METHODS: Using Optum’s de-identified Clinformatics® Data Mart Database, we identified insured patients with heart failure with reduced ejection fraction (HFrEF) who filled HF prescriptions for components of GDMT (“conventional GDMT:” i.e., ACEi or ARB, and beta-blocker) or first-line therapy from the most recent US guidelines (“2022 GDMT:” i.e., ARNi, MRA, beta-blocker, SGLT2i) between Jan2020 and Mar2022. We describe these cohorts and compare all-cause death or WHF events by history of WHF at GDMT initiation.

RESULTS: Overall, 26,517 and 2,775 patients were in the conventional and 2022 GDMT cohorts, respectively. The conventional GDMT cohort was older (73 vs. 66 years), and more were female (41% vs. 33%) and white (67% vs. 60%). They had more comorbidities, but lower percentages of patients receiving conventional GDMT had diabetes mellitus (53% vs. 67%) and PVD (37% vs. 58%). Roughly half of the sample had a WHF event (conventional GDMT: 51%, 2022 GDMT: 47%). In patients on conventional GDMT, those with WHF had 71 excess deaths, 210 more patients experienced 364 HF hospitalizations, and 77 additional patients received 197 IV diuretic administrations per 1000 patients per year compared with those without WHF. In patients on 2022 GDMT, those with WHF had 70 excess deaths, 216 more patients experienced 309 HF hospitalizations and 47 patients received 94 IV diuretic administrations per 1000 patients per year compared with those without WHF.

CONCLUSIONS: Risk of subsequent WHF events and death was higher in patients with existing WHF even when receiving the most recent GDMT. Observations underscore the need for additional therapies and optimized care in this high-risk population.