Effectiveness of tirzepatide in patients with HFpEF using a target trial emulation retrospective cohort study
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Key result
Tirzepatide use was associated with a 48% lower risk of the composite of heart failure exacerbation and all-cause mortality (HR 0.52) compared to no use in patients with HFpEF.
Why the study?
Tirzepatide has shown promise in improving metabolic and cardiovascular profiles in obesity, but its potential benefits in patients with HFpEF remain unclear.
Does tirzepatide reduce the composite outcome of heart failure exacerbation and all-cause mortality in patients with HFpEF?
Population
14,154 patients with HFpEF after 1:1 propensity score matching
Comparison
Tirzepatide use vs propensity score-matched control
Design
Retrospective cohort study
Authors
Discussion
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Implication
May support tirzepatide in HFpEF; hypothesis-generating and requires randomized confirmation.
Study Design
Type
Cohort (n=14,154)
Multicenter
Yes
Structured PICO
Does tirzepatide reduce the composite outcome of heart failure exacerbation and all-cause mortality in patients with HFpEF?
P
Population
14,154 adult patients with heart failure with preserved ejection fraction (HFpEF), matched 1:1 for baseline characteristics, followed for up to 1 year.
E
Exposure
Tirzepatide
C
Comparator
Propensity score matched control cohort
O
Outcome
Composite outcome of heart failure exacerbation and all-cause mortalitycomposite
Main Result
Hazard Ratio: 0.52 (95% CI 0.42–0.63)
Absolute Event Rate: 3.09% vs 6.55%
p-value: p=< 0.001
In a real-world retrospective cohort, tirzepatide use in patients with HFpEF was associated with significantly lower risks of mortality, heart failure exacerbation, and major adverse cardiovascular and kidney events.
Limitations
- Registry-based data may have issues with misidentification and under-representation
- Reliance on diagnostic codes to identify variables and outcomes may lead to misclassification
- Treatment duration could not be determined from the database
- Unmeasured variables may have influenced the outcomes, introducing potential confounding
- Potential immortal time bias due to lack of a placebo group
- Loss to follow-up and right-censoring inherent to EHR-based data
- Unable to directly characterize the distribution of time to tirzepatide initiation
- Unable to define the causes of mortality
Cite This Study
Lin et al. (2025) conducted a cohort in Heart failure with preserved ejection fraction (HFpEF) (n=14,154). Tirzepatide vs. No tirzepatide use was evaluated on Composite of heart failure exacerbation and all-cause mortality (HR 0.52, 95% CI 0.42-0.63, p=< 0.001). Tirzepatide use was associated with a 48% lower risk of the composite of heart failure exacerbation and all-cause mortality (HR 0.52) compared to no use in patients with HFpEF.
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