Heart failure & cardiomyopathies
Interplay of Chronic Kidney Disease and the Effects of Tirzepatide in Patients With Heart Failure, Preserved Ejection Fraction, and Obesity: The SUMMIT Trial
Authors' conclusion
The triad of obesity, HFpEF, and CKD identifies patients with considerable functional impairment and an unfavorable prognosis, who nevertheless respond favorably to tirzepatide. Long-term tirzepatide improves renal function (both by cystatin C and creatinine), but the measurement of eGFR in patients with obesity receiving incretin-based drugs is likely to be skewed by the effects of fat and muscle mass (and by changes in body composition) on the synthesis of both cystatin C and creatinine.
Study context
- Population
- Patients with heart failure with a preserved ejection fraction (HFpEF) and BMI ≥30 kg/m², with or without chronic kidney disease (CKD)
- Participants
- 731 patients
- Comparison
- Tirzepatide vs placebo, by CKD status
- Primary endpoint
- Influence of CKD on clinical responses to tirzepatide (CV death or worsening HF events; KCCQ-CSS) and tirzepatide-related changes in eGFR (creatinine- and cystatin C-based)
- Follow-up
- Median 104 weeks; KCCQ-CSS and eGFR at 52 weeks
Methodological detailsenriched for participants with CKD, Patients received placebo or tirzepatide for a median of 104 weeks, estimated glomerular filtration rate (eGFR) assessed at randomization and after 12, 24 and 52 weeks by creatinine- and cystatin C-based formulae
- Enriched for participants with CKD
- Patients received placebo or tirzepatide for a median of 104 weeks
- eGFR assessed at randomization and after 12, 24 and 52 weeks by creatinine- and cystatin C-based formulae
Primary result
As reported in the abstract
- CKD did not influence the effect of tirzepatide to reduce the relative risk of major adverse HF events and to improve Kansas City Cardiomyopathy Questionnaire Clinical Summary Score (KCCQ-CSS), quality of life and functional capacity
- Absolute risk reduction in primary events numerically greater in patients with CKD
Further findings
HF severity in patients with CKD
- Increase in risk of worsening HF events
- 2-fold
- Worse functional class, KCCQ-CSS and 6-minute walk distance; higher NT-proBNP and cardiac troponin T
Baseline eGFR-cystatin C vs eGFR-creatinine
- eGFR-cystatin C consistently lower than eGFR-creatinine, with significant individual variance
- ≈9 mL/min/1.73 m²
eGFR with tirzepatide · 12 and 52 weeks
- Increase in eGFR at 52 weeks by both formulae, with considerable individual discordance
- Decline in eGFR at 12 weeks with eGFR-creatinine (not eGFR-cystatin C)
- Improvement at 52 weeks in all patients by cystatin C, but only in patients with CKD by eGFR-creatinine
Original publication
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