Prescription of Guideline-Directed Medical Therapy in Heart Failure: Impact on Mortality and Readmission

AIMS: The 2021 European heart failure (HF) guidelines recommend the combination of four drugs as a standard therapy (angiotensin-converting enzyme inhibitor [ACEI]/angiotensin receptor blocker [ARB]/angiotensin receptor-neprilysin inhibitor [ARNI]; beta-blocker (BB); mineralocorticoid receptor antagonist [MRA]; sodium-glucose co-transporter 2 inhibitor [SGLT2i]) in patients with heart failure and reduced ejection fraction (HFrEF). We investigated if the use of this combined treatment (as opposed to the outdated two-drug ACEI/ARB and BB therapy) yields a favourable outcome regarding mortality and readmission and evaluated whether an increase in adoption of the newly endorsed therapy can already be observed in clinical routine. METHODS AND RESULTS: We included anonymous data from all patients who were insured at Germany's largest health insurer (Allgemeine Ortskrankenkasse [AOK]) and had a claims record for hospitalization (2019-2021) with the main diagnosis of HF. Mortality and readmission within 91-365 days following the index stay were analysed, and the impact of medication on outcome was compared. 315 342 cases of hospitalization due to HF were included (median 80 years [IQR 72-86], 53.7% female). HF drug prescription rates were as follows: ACEI 46.3%, ARB 31.8%, ARNI 12.1%, BB 80.9%, MRA 35.6%, SGLT2i 7.3%. Treatment combinations were prescribed in 35.9% (two-drug) and 3.7% (four-drug). Total mortality was 18.0%, all-cause readmission 32.0%, and HF readmission 16.0%. Mortality risk was significantly lower (adjusted HR = 0.92 [95% CI 0.86-0.97]) with the four- versus two-drug treatment. Kaplan-Meier survival was 88.2% for the four-drug therapy [95% CI: 87.6%-88.8%] and 83.1% for the two-drug therapy [95% CI: 82.9%-83.3%]). Similar benefits were visible for the readmission rates due to all causes (HR = 0.76 [0.73-0.80]) and readmission due to HF (HR = 0.90 [0.85-0.95]). CONCLUSIONS: Our study suggests that the newly recommended four-drug therapy may lead to lower mortality and readmission rates compared to the outdated two-drug therapy. However, the overall adoption of the four-drug therapy remains limited.