Research Article|Articles in Press

Time to Triple Therapy in Patients With de Novo Heart Failure With Reduced Ejection Fraction: a Population-Based Study

Published:February 06, 2023DOI:


      • Despite long-standing guideline recommendations, triple therapy remains under-used in clinical practice, with only one-fifth of patients with heart failure (HF) and reduced ejection fraction (HFrEF) receiving all 3 classes within 1 year after the index HF diagnosis.
      • Younger patients with lower LVEF, higher natriuretic peptide levels and better renal function were more likely to be initiated on triple therapy, and even after adjustment for potential confounders, triple therapy was associated with better clinical outcomes.
      • Identifying barriers to the timely initiation of triple therapy could help clinicians and policymakers in devising implementation strategies to improve the initiation of quadruple therapy.



      Quadruple therapy is recommended for the management of patients with heart failure (HF) and reduced ejection fraction (HFrEF). In order to provide background and identify barriers to quadruple therapy, in this study, the aim was to explore the time to initiation of triple therapy in a population-based cohort of patients with de novo HF.


      Adult patients with de novo hospital or emergency department (ED) diagnosis of HF between April 1, 2008, and March 31, 2018, in Alberta, Canada, were included and were linked to echocardiography data to identify patients with HFrEF (EF ≤ 40%). Any treatment with angiotensin-converting enzyme inhibitors/ angiotensin receptor blockers/ angiotensin receptor neprilysin inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was captured if prescribed for ≥ 28 days and filled at least once during the 12 months after the index episode.


      Among 14,092 patients with de novo HF and available echocardiography data, 54.9% had HFrEF. By 1 year after diagnosis, of those in the HFrEF cohort, 9.5% had received no therapy, 27.5% monotherapy, 41.6% dual therapy, and 21.4% triple therapy. The median (interquartile range) of time to mono-, dual- and triple therapy in patients with HFrEF were 1 (0, 26), 8 (0, 44), and 14 (0, 52) days, respectively. Patients who received triple therapy were younger, more likely to be male and to have higher frequencies of coronary artery disease, higher glomerular filtration rates and lower left ventricular ejection fraction levels compared to their counterparts. Patients with triple therapy had lower rates of clinical outcomes compared to those on no, mono or dual therapy (adjusted hazard ratio 0.15, 95% confidence interval 0.13, 0.17 for the composite outcome of death, hospitalization due to HF, or ED visit due to HF).


      Despite guideline recommendations, triple therapy is underused and is slowly deployed in patients with HFrEF, even after hospitalization and ED presentation.

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      Linked Article

      • Time to Quadruple Guideline-Directed Medical Therapy as a Key Performance Measure for Heart Failure
        Journal of Cardiac Failure
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          The prevalence of heart failure (HF) continues to steadily rise and now more than 64 million people globally carry the diagnosis.1 Together with a 5-year survival rate of ∼50% and high rates of hospitalization, there are few other conditions across medicine that have such an unfortunate combination of being exceedingly common, morbid, and deadly.2 Fortunately, for patients with HF with reduced ejection (HFrEF), there are now multiple medications definitively proven to substantially increase survival, reduce hospitalizations, and improve patient quality of life.
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