Heart failure drug titration, discontinuation, mortality and heart failure hospitalization risk: a multinational observational study (US, UK and Sweden)

Abstract

Aims Use and dosing of guideline‐directed medical therapy (GDMT) in patients with heart failure (HF) have been shown to be suboptimal. Among new users of GDMT in HF, we followed the real‐life patterns of dose titration and discontinuation of angiotensin‐converting enzyme inhibitors (ACEi), angiotensin receptor blockers (ARB), beta‐blockers, mineralocorticoid receptor antagonists (MRA) and angiotensin receptor–neprilysin inhibitors (ARNI). Methods and results New users were identified in health care databases in Sweden, UK and US between 2016–2019. Inclusion criterion was a recent HF hospitalization (HHF) triggering the initiation of GDMT. Patients were grouped by GDMT, i.e. ACEi, ARB, beta‐blocker, MRA and ARNI, and stratified by initial dose. Follow‐up was 12 months, until death or study end. Outcomes were dose titration within each drug class, discontinuation and first HHF or death. Dose/discontinuation follow‐up was assessed daily based on the coverage length of a filled prescription and reported on day 365. New users of ACEi (n = 8426), ARB (n = 2303), beta‐blockers (n = 10 476), MRA (n = 17 421), and ARNI (n = 29 546) were identified. Over 12 months, target dose achievement was 15%, 10%, 12%, 30%, and discontinuation was 55%, 33%, 24% and 27% for ACEi, ARB, beta‐blockers and ARNI, respectively. MRA was rarely titrated and discontinuation rates were high (40%). Event rates for HHF or death ranged from 40.0–86.9 per 100 patient‐years across the treatment groups. Conclusion Despite high risk of clinical events following HHF, new initiation of GDMT was followed by consistent patterns of low up‐titration and early GDMT discontinuation in three countries with different health care and economies. Our data highlight the urgent need for moving away from long sequential approach when initiating HF treatment and for improving just‐in‐time decision support for patients and health care providers.

Advanced heart failure: guideline‐directed medical therapy, diuretics, inotropes, and palliative care

“…Neurohormonal antagonists, including angiotensin-converting enzyme inhibitors (ACEi), angiotensin receptor blockers, angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists, and sodiumglucose co-transporter 2 (SGLT2) inhibitors, are the mainstay of HFrEF treatment, improving the clinical course of HF. 7,[12][13][14][15][16] Adherence to GDMT is associated with improved outcome. [17][18][19][20][21][22] Data from population-based studies reported a decline in HF-related hospitalizations and mortality over the last two decades.…”

The Gap to Fill: Rationale for Rapid Initiation and Optimal Titration of Comprehensive Disease-modifying Medical Therapy for Heart Failure with Reduced Ejection Fraction

“…A recent multinational study analysing healthcare databases from the US, UK and Sweden cements the findings of suboptimal titration, as well as high rates of premature discontinuation. [ 23 ] In patients who have been hospitalised with a recent diagnosis of HF and subsequently initiated on GDMT, after a follow-up of 12 months, target dosage rates were 15% for ACEIs, 10% for ARBs, 12% for β-blockers and 30% for ARNIs. MRAs, in contrast, reached target dose at a rate of 60%.…”

“…Discontinuation rates were far higher than CHAMP-HF, reaching 55% for ACEIs, 33% for ARBs, 24% for β-blockers, 27% for ARNIs and 40% for MRAs. [ 19 , 23 ]…”

Evidence-based Therapy in Older Patients with Heart Failure with Reduced Ejection Fraction

“…Age is a recognised major determinant of low adherence to GDMT in HFrEF. [ 17 , 18 , 20 , 21 ] In the CHAMP-HF registry, older age was associated with the lower use of β-blockers, MRAs and angiotensin receptor–neprilysin inhibitor (ARNI), and, at the 12-month follow-up, dose maximisation was less likely with increasing age. [ 18 , 39 ] Similarly, in the US GWTG-HF registry, there was a decreasing gradient in the use of GDMT with increasing age, although the authors correctly highlighted that the prescription rate was high overall also in the oldest category (i.e.…”