ArticleJournal of the American Heart Association2025
Comparison of Quadruple Therapy Sequencing Strategies for Heart Failure With Reduced Ejection Fraction.
Article in Journal of the American Heart Association, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
1 citing paper in PubMed.
- Vericiguat in the Post-Stabilization Phase of HFrEF: Targeting Residual Risk Across the Ischemia-Decompensation Continuum.International journal of molecular sciences · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGuidelines unanimously recommend quadruple therapy for patients with heart failure with reduced ejection fraction (HFrEF), yet direct comparative evidence is lacking to recommend a specific order of initiating and titrating these agents (or "sequencing strategy"). In the absence of randomized evidence, we aimed to compare the 1-year efficacy and harms of proposed HFrEF quadruple therapy sequencing strategies using a microsimulation model.
methodsWe conducted a microsimulation study to compare 6 different HFrEF medication sequencing strategies (emulating the range of conventional, 2-drug, and rapid or simultaneous strategies), each with 2 versions (twice-weekly/weekly medication adjustments), applied to treatment-naïve outpatients with HFrEF. We modeled death; total heart failure hospitalization (including recurrent events); the composite of death or first heart failure hospitalization; and adverse drug events (bradycardia, hyperkalemia, hypotension, and renal impairment) at 1 year.
resultsAt 1 year, an estimated 15.3 per 100 patients died without treatment compared with 6.9 per 100 patients with the conventional sequence adjusted biweekly, and 5.2 to 6.4 per 100 patients with other sequencing strategies. The incidence of heart failure hospitalization decreased from 31.5 per 100 patients without treatment to 11.4 per 100 patients with conventional sequencing adjusted biweekly, and 7.3 to 9.4 per 100 patients with other strategies. The cumulative incidence of total adverse drug events per 100 patients was 14.2 to 16.0 across sequencing strategies.
conclusionsFor treatment-naïve outpatients with HFrEF, sequencing strategies that started 2 to 4 medications on the first visit, followed by titration biweekly or weekly, were associated with lower risk of death and heart failure hospitalization, and similar risk of treatment-related adverse events, at 1 year compared with conventional sequencing.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.