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

Nariman Sepehrvand; Majid Nabipoor; Erik Youngson; Finlay A McAlister; Justin A Ezekowitz

doi:10.1016/j.cardfail.2023.01.005

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

J Card Fail. 2023 May;29(5):719-729. doi: 10.1016/j.cardfail.2023.01.005. Epub 2023 Feb 7.

Authors

Nariman Sepehrvand¹, Majid Nabipoor², Erik Youngson², Finlay A McAlister³, Justin A Ezekowitz⁴

Affiliations

¹ Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
² Patient Health Outcomes Research and Clinical Effectiveness Unit, University of Alberta, Edmonton, Alberta, Canada.
³ Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; Department of Medicine, University of Alberta, Edmonton, Alberta, Canada; Patient Health Outcomes Research and Clinical Effectiveness Unit, University of Alberta, Edmonton, Alberta, Canada.
⁴ Canadian VIGOUR Centre, University of Alberta, Edmonton, Alberta, Canada; Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada. Electronic address: jae2@ualberta.ca.

PMID: 36754252
DOI: 10.1016/j.cardfail.2023.01.005

Abstract

Background: 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.

Methods: 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.

Results: 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).

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

Keywords: Heart failure; guideline-directed medical therapy; heart failure with reduced ejection fraction; triple therapy.

MeSH terms

Adrenergic beta-Antagonists / therapeutic use
Adult
Alberta / epidemiology
Angiotensin Receptor Antagonists / therapeutic use
Angiotensin-Converting Enzyme Inhibitors / therapeutic use
Female
Heart Failure* / diagnosis
Heart Failure* / drug therapy
Heart Failure* / epidemiology
Humans
Male
Mineralocorticoid Receptor Antagonists / therapeutic use
Stroke Volume
Ventricular Function, Left

Substances

Angiotensin-Converting Enzyme Inhibitors
Adrenergic beta-Antagonists
Mineralocorticoid Receptor Antagonists
Angiotensin Receptor Antagonists