May 14, 2025Nature Communications20 citationsOpen Access
Effectiveness of tirzepatide in patients with HFpEF using a target trial emulation retrospective cohort study
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.
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
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.
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
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
Abstract
Tirzepatide, a dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has shown promise in improving metabolic and cardiovascular profiles in patients with obesity. However, its potential benefits in patients with heart failure with preserved ejection fraction (HFpEF) remain unclear. We conducted a real-world, retrospective cohort study using the TriNetX global database. A total of 14,154 patients with HFpEF were included after 1:1 propensity score matching. Tirzepatide use was associated with significantly lower risks of the primary composite outcome of heart failure exacerbation and all-cause mortality (HR 0.52), as well as reductions in major adverse cardiovascular events (HR 0.64) and major adverse kidney events (HR 0.44). Subgroup analyses demonstrated consistent benefits across different strata. Sensitivity analyses using alternative exposure definitions confirmed the robustness of the findings. These results support the potential clinical utility of tirzepatide in HFpEF management and warrant further investigation in randomized controlled trials. Tirzepatide has shown promise for treatment of obesity but its effects in heart failure are unknown. Using real-world data from over 14,000 patients, the authors show that tirzepatide is associated with lower risks of death, heart failure worsening, cardiovascular events, and kidney complications in people with preserved ejection fraction heart failure.