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

Gianluigi Savarese, Johan Bodegard, Anna Norhammar, Peter Sartipy, Marcus Thuresson, Martin R. Cowie, Gregg C. Fonarow, Muthiah Vaduganathan, Andrew J.S. Coats

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1499-1511
Number of pages13
JournalEuropean Journal of Heart Failure
Issue number9
Publication statusPublished - Sep 2021
Externally publishedYes


  • Angiotensin receptor blocker
  • Angiotensin receptor–neprilysin inhibitor
  • Angiotensin-converting enzyme inhibitor
  • Beta-blocker
  • Guideline-directed medical therapy
  • Heart failure with reduced ejection fraction
  • Mineralocorticoid receptor antagonist

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine


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