Effects of tirzepatide on circulatory overload and end-organ damage in heart failure with preserved ejection fraction and obesity: a secondary analysis of the SUMMIT trial
Abstract
Patients with obesity-related heart failure with preserved ejection fraction (HFpEF) display circulatory volume expansion and pressure overload contributing to cardiovascular–kidney end-organ damage. In the SUMMIT trial, patients with HFpEF and obesity were randomized to the long-acting glucose-dependent insulinotropic polypeptide receptor and glucagon-like peptide-1 receptor agonist tirzepatide (n = 364, 200 women) or placebo (n = 367, 193 women). As reported separately, tirzepatide decreased cardiovascular death or worsening heart failure. Here, in this mechanistic secondary analysis of the SUMMIT trial, tirzepatide treatment at 52 weeks, as compared with placebo, reduced systolic blood pressure (estimated treatment difference (ETD) −5 mmHg, 95% confidence interval (CI) −7 to −3; P < 0.001), decreased estimated blood volume (ETD −0.58 l, 95% CI −0.63 to −0.52; P < 0.001) and reduced C-reactive protein levels (ETD −37.2%, 95% CI −45.7 to −27.3; P < 0.001). These changes were coupled with an increase in estimated glomerular filtration rate (ETD 2.90 ml min−1 1.73 m−2 yr−1, 95% CI 0.94 to 4.86; P = 0.004), a decrease in urine albumin–creatinine ratio (ETD 24 weeks, −25.0%, 95% CI −36 to −13%; P < 0.001; 52 weeks, −15%, 95% CI −28 to 0.1; P = 0.051), a reduction in N-terminal prohormone B-type natriuretic peptide levels (ETD 52 weeks −10.5%, 95% CI −20.7 to 1.0%; P = 0.07) and a reduction in troponin T levels (ETD 52 weeks −10.4%, 95% CI −16.7 to −3.6; P = 0.003). In post hoc…
How strong is the evidence?
Evidence Hub reads this as a secondary / pooled analysis, done in people. Its evidence level is 3 of 5 (Moderate · trial / cohort / secondary analysis). Trials without a large randomized design, cohorts and secondary analyses give moderate evidence. Reported size: 367 participants or records.
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