Real-world use of guideline-directed therapy for heart failure: Insights from the Danish Heart Failure Registry

Abstract

Aims: We aimed to assess real-world implementation of guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction (HFrEF) and its association with mortality and hospitalization.

Methods: We analysed 46 816 incident HFrEF patients from the Danish Heart Failure Registry (2008-2022). We examined the utilization of GDMT-renin-angiotensin system inhibitors (RASi), beta-blockers, mineralocorticoid receptor antagonists (MRAs) and sodium-glucose cotransporter-2 inhibitors (SGLT2i)-at 4, 8 and 12 weeks of follow-up according to the European Society of Cardiology guidelines within the intervals 2008-2011, 2012-2015, 2016-2020 and 2021-2022. Using Cox regression, we assessed the associations between GDMTs [none (reference), 1-2 GDMTs, and 3-4 GDMTs] initiated at 4, 8 and 12 weeks and 1 and 3 year mortality (all-cause and cardiovascular) and hospitalization (all-cause and HF).

Results: Between 2008-2011 and 2021-2022, RASi utilization at 4 weeks of follow-up was 93.2% and 93.7%, respectively, and at 12 weeks of follow-up, 97.2% and 97.8%, respectively. Beta-blocker use was 81.1% and 78.2% at 4 weeks and 89.6% and 90.4% at 12 weeks of follow-up while MRA utilization was 27.2% and 34.6% at 4 weeks and 32.6% and 52.2% at 12 weeks of follow-up. The SGLT2i use at 4 weeks increased from 0.0% to 21.3%, and at 12 weeks of follow-up from 3.2% to 35.8% between 2016-2020 and 2021-2022. The initiation of GDMTs at 4 weeks of follow-up was associated with lower adjusted hazard ratios (HRs) [95% confidence intervals (CI)] for 1 year all-cause mortality [1-2 GDMTs: 0.73 (95% CI: 0.61-0.86), 3-4 GDMTs: 0.65 (95% CI: 0.55-0.78)], 3 year all-cause mortality [1-2 GDMTs: 0.75 (95% CI: 0.66-0.86); 3-4 GDMTs: 0.67 (95% CI: 0.59-0.76)] and 3 year cardiovascular mortality [1-2 GDMTs: 0.74 (95% CI: 0.62-0.89); 3-4 GDMTs: 0.72 (95% CI: 0.59-0.87)]. Lower adjusted HRs were also observed for 1 year all-cause hospitalization [1-2 GDMTs: 0.80 (95% CI: 0.75-0.86); 3-4 GDMTs: 0.78 (95% CI: 0.73-0.84)] and 3 year all-cause hospitalization [1-2 GDMTs: 0.77 (95% CI: 0.72-0.83); 3-4 GDMTs: 0.77 (95% CI: 0.71-0.82)].

Conclusions: We demonstrated high use of RASi and beta-blockers and rising use of MRA and SGLT2i, reflecting rapid adaption to guidelines changes in incident HFrEF patients. Early GDMT initiation was associated with lower 1 and 3 year mortality and all-cause hospitalization. Upfront treatment with GDMT, according to the latest guidelines, is crucial.

Keywords: guidelines; guideline‐directed medical therapy; heart failure; implementation; outcomes; utilization.

Figure 1

Guideline‐directed medical therapy (GDMT) initiated within 4, 8 and 12 weeks after the diagnosis of heart failure with reduced ejection fraction patients, stratified by the guidelines index year. ACEi/ARB, angiotensin‐converting enzyme inhibitors/angiotensin‐receptor blockers; ARNi, angiotensin receptor‐neprilysin inhibitors; MRA, mineralocorticoid antagonists; RASi, renin–angiotensin system inhibitors; SGLT2i, sodium‐glucose cotransporter‐2 inhibitors.

Figure 2

The average number of guideline‐directed medical therapy (GDMT) initiated within 4, 8 and 12 weeks after the diagnosis of heart failure with reduced ejection fraction patients, stratified by guidelines index year. Adjusted for age at index, sex, frailty, inpatient or outpatient at index contact, New York Heart Association functional classification, left ventricular ejection fraction, myocardial infarction, hypertension, stroke, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, s‐creatinine level, smoking and alcohol habits, civil status, educational level, family income and index period. AV, average; GDMTs; guideline‐directed medical therapies.

Figure 3

Unadjusted hazard ratios for 1 and 3 year all‐cause and cardiovascular mortality based on the number of guideline‐directed medical therapies (GDMTs) initiated at 4, 8 and 12 weeks after diagnosing heart failure with reduced ejection fraction. CI, confidence interval; CV, cardiovascular; GDMTs; guideline‐directed medical therapies; HR, hazard ratio.

Figure 4

Adjusted hazard ratios for 1 and 3 year all‐cause and cardiovascular mortality based on the number of guideline‐directed medical therapies (GDMTs) initiated at 4, 8 and 12 weeks after diagnosing heart failure with reduced ejection fraction. Adjusted for age at index, sex, frailty, inpatient or outpatient at index contact, New York Heart Association functional classification, left ventricular ejection fraction, myocardial infarction, hypertension, stroke, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, s‐creatinine level, smoking and alcohol habits, civil status, educational level, family income and index period. CI, confidence interval; CV, cardiovascular; GDMTs; guideline‐directed medical therapies; HR, hazard ratio.

Figure 5

Unadjusted hazard ratios for 1 and 3 year all‐cause and HF hospitalization based on the number of guideline‐directed medical therapies (GDMTs) initiated at 4, 8 and 12 weeks after diagnosing heart failure with reduced ejection fraction. CI, confidence interval; Guideline‐directed medical therapies; HR, hazard ratio.

Figure 6

Adjusted hazard ratios for 1 and 3 year all‐cause and HF hospitalization based on the number of guideline‐directed medical therapies (GDMTs) initiated at 4, 8 and 12 weeks after diagnosing heart failure with reduced ejection fraction. Adjusted for age at index, sex, frailty, inpatient or outpatient at index contact, New York Heart Association functional classification, left ventricular ejection fraction, myocardial infarction, hypertension, stroke, atrial fibrillation, chronic obstructive pulmonary disease, diabetes, s‐creatinine level, smoking and alcohol habits, civil status, educational level, family income and index period. CI, confidence interval; guideline‐directed medical therapies; HR, hazard ratio.

Figure 7

Prevalence of device therapies at baseline and 12 months after the diagnosis of heart failure with reduced ejection fraction patients, stratified by the guidelines index year. CI, confidence interval; CRT‐D, cardiac resynchronization therapy with defibrillator; CRT‐P cardiac resynchronization therapy‐pacemaker; ICD, implantable cardioverter defibrillator.