The impact of worsening heart failure (WHF) status on subsequent outcomes among patients with HFrEF: History of WHF events is associated with worse subsequent outcomes regardless of extent of GDMT
Authors: Coyle C , Ru B , Ambrosy A P , Mcmullen C J , Stevenson A S , Ai L , Bash L D , Gaggin H K 
Published: November 2023

Abstract

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

Methods
Using Optum’s de-identified Clinformatics® Data Mart Database, we identified 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. The ongoing risk of HF hospitalizations (HFH), receipt of IV diuretics, and all-cause death, was assessed by history of (HFH, receipt of IV diuresis in past 12 months) WHF. Event rates reflect counts of first events, whereas cumulative incidence is first and recurrent events. Both are presented per 1,000 person-years.

Results
Conventional GDMT Cohort: Overall, 26,517 were in the cohort and 51% had WHF. Patients with and without WHF were alike in age (72 vs. 73 years) and a similar proportion were female (43% vs. 40%), and white (67% vs. 67%) (Table). Per 1,000 person-years, the event rates for death, HFH, and IV diuresis were 109, 404, and 106 among patients with WHF and 38, 194, and 29 among patients without WHF, respectively. The cumulative incidence, per 1,000 person-years, for HFH and IV diuretics use among those with WHF were 622 and 241 compared to 258 and 44 among those without WHF (Table). The time to WHF event or death was shorter for patients with WHF (Figure) and HR for all-cause death or WHF was 1.91 for those with WHF compared to those without.
2022 GDMT Cohort: There were 2,775 patients receiving 2022 GDMT and just under half (47%) had WHF. Patients with and without WHF were both an average of 66 years of age, one-third were female, and 60% were white (Table). The event rates (per 1,000 person-years) for death, HFH, and IV diuretic use among those with WHF were 176, 395, and 87 compared to 106, 179, and 40, among those without WHF, respectively (Table). The cumulative incidence (per 1,000 person-years) for HFH and IV diuresis were 577 and 157 among patients with WHF and 268 and 63 among patients without WHF. The time to WHF event or death was also shorter for patients with WHF (Figure). The HR for all-cause death or WHF event comparing patients with and without WHF was 2.28.

Conclusion
Our study quantified the excess risk of HF morbidity and all-cause death associated with WHF, regardless of extent of GDMT. WHF resulted in higher hospitalizations, morbidity, and deaths and was the strongest predictor of subsequent WHF and all-cause death. This places patients with WHF in a high-risk group. Results can help clinicians better assess the clinical trajectory of their patients and underscore the need for additional therapies and optimized care.Table.Patient CharacteristicsFigure.Clinical Trajectory