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Patterns of Heart Failure Drug Treatment
Quick Takes
- Rates of ARNI and SGLT-2i initiation within 12 months of HF hospitalization were delayed in the United States, Japan, and Sweden compared with other components of GDMT.
- At 12 months of follow-up, rates of GDMT discontinuation were high with slow rates of up-titration in all three countries but these rates were highest in the United States.
- SGLT-2i had the highest rates of target dose achievement and were persistent upon follow-up.
Study Questions:
What are patterns of use of guideline-directed medical therapy (GDMT) after hospitalization for heart failure (HF) in the contemporary, real-world?
Methods:
The EVOLUTION HF study used a multinational, observational cohort enrolling patients from Japan, Sweden, and the United States using electronic health records or claims data. It included all adults with at least 12 months of continual data available who were newly initiated on any component of GDMT within 12 months of HF hospitalization. GDMT initiation, dose titration, and discontinuation analyses were performed.
Results:
Overall, 266,589 patients initiated on at least one component of GDMT within 12 months of HF hospitalization were included. Patients initiated on an angiotensin receptor-neprilysin inhibitor (ARNI) or sodium-glucose cotransporter-2 inhibitor (SGLT-2i) were younger in all three countries, less likely to be women, with a higher burden of comorbidities. Time to initiation after first HF diagnosis for ARNI and SGLT-2i was longer compared with other classes of medications. Use was delayed for patients with kidney disease and type 2 diabetes. The proportion of patients receiving ARNI or SGLT-2i after HF hospitalization was lower compared to other GDMT classes across all three countries. ARNI/SGLT-2i use was more likely in patients on other GDMT classes.
At 12-month follow-up, pooled rates of discontinuation were 23% for SGLT-2i, 26% for ARNI, 38% for angiotensin-converting enzyme inhibitor (ACEi), 33% for angiotensin receptor blocker (ARB), 25% for beta-blocker (BB), and 42% for mineralocorticoid receptor antagonist (MRA). Target dose was achieved in 76% for SGLT-2i, 28% for ARNI, 20% for ACEi, 7% for ARB, 7% for BB, and 5% for MRA. For all GDMT, discontinuation and slow up-titration was more common in the United States than in Sweden or Japan.
Conclusions:
In a multinational cohort, ARNI and SGLT-2i initiation was delayed after HF hospitalization. For all components of GDMT, high rates of discontinuation were noted across all three countries, but rates were highest in the United States compared to Sweden and Japan. Target dose was achieved frequently for SGLT-2i and was much lower for other classes of GDMT.
Perspective:
In the last decade, GDMT for HF has advanced leaps and bounds. Despite significant improvements in mortality and morbidity with appropriately dosed GDMT, several cohorts in the United States have persistently demonstrated lower rates of use of ARNI and SGLT-2i and slow up-titration of all GDMT components with poor persistence. In this large multinational cohort, these findings were corroborated for Japan and Sweden as well. ARNI and SGLT-2i initiation was delayed in all three countries, with high rates of discontinuation and slow rates of up-titration for all GDMT. As a class, SGLT-2i were associated with the highest rates of target dose achievement, as no dose titration is needed for this class, and with the highest persistence. Consistent with prior studies, women and patients with higher comorbidity burden such as kidney disease and diabetes, who are more likely to benefit from GDMT, were less likely to receive appropriate therapy for HF. Rates of discontinuation and slow up-titration were notably higher in the United States compared with Sweden and Japan. These findings continue to highlight large gaps that remain in real-world clinical practice in the treatment of HF.
Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Acute Heart Failure, Heart Failure and Cardiac Biomarkers
Keywords: Adrenergic beta-Antagonists, Angiotensin Receptor Antagonists, Angiotensin-Converting Enzyme Inhibitors, Antihypertensive Agents, Comorbidity, Diabetes Mellitus, Type 2, Heart Failure, Kidney Diseases, Mineralocorticoid Receptor Antagonists, Neprilysin, Primary Prevention, Secondary Prevention, Sodium-Glucose Transporter 2 Inhibitors, Treatment Outcome
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