Trial reportCirculation. Heart failure2026
Modest Contribution of Bradykinin to Blood Pressure Reduction by Sacubitril/Valsartan in Chronic Heart Failure.
Trial report in Circulation. Heart failure, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04113109 (Mechanisms Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 2), which is not on this map. Cited by 1 paper.
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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.
Mechanisms Underlying Hypotensive Response to ARB/NEP Inhibition - Aim 2
Who cites it
1 citing paper in PubMed.
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Authors and funding
9 authors.
Funding
Abstract
backgroundSymptomatic hypotension can limit sacubitril/valsartan therapy. Neprilysin inhibition may augment vasodilators, such as bradykinin. We hypothesized that bradykinin contributes to blood pressure (BP) lowering with sacubitril/valsartan in stable ambulatory patients with heart failure and reduced ejection fraction <50%.
methodsIn a randomized, double-blind crossover trial, participants received intravenous infusion of the bradykinin B2 receptor inhibitor icatibant and a matching placebo for 6 hours following sacubitril/valsartan dosing at acute initiation (n=36) and after 8 weeks of chronic therapy (n=30). The primary end point was maximal change in mean arterial pressure (MAP). Plasma natriuretic peptides, urine cyclic GMP, urine volume, sodium excretion, renal plasma flow, and renovascular resistance were measured.
resultsThe first dose of sacubitril/valsartan (50 mg) significantly lowered MAP by a mean maximum of ≈10 mm Hg, which was similar during icatibant and placebo. Within 6 hours after the first sacubitril/valsartan dose, plasma ANP (atrial natriuretic peptide [1-28]) and urine cGMP/creatinine increased significantly, whereas B-type NP (1-32) and NT-proBNP (N-terminal pro B-type natriuretic peptide) did not. Icatibant partially blunted the rise in urine cGMP/creatinine, but did not affect other parameters. After 8 weeks of sacubitril/valsartan titrated to maximally tolerated doses, baseline ANP (1-28) remained increased, and baseline MAP and NT-proBNP were decreased compared with before sacubitril/valsartan initiation. MAP decreased further after dose administration of sacubitril/valsartan, and the mean maximal reduction in MAP was significantly attenuated during icatibant compared with placebo (9 versus 12 mm Hg;
conclusionsBP lowering with sacubitril/valsartan occurs with both acute and chronic dosing. ANP (1-28) appears to mediate the initial BP reduction, whereas bradykinin contributes to BP lowering after dosing during chronic therapy. Clarifying these mechanisms may inform clinical management to optimize the benefit of this important heart failure and reduced ejection fraction therapy. REGISTRATION: URL: https://www.clinicaltrials.gov; Unique identifier: NCT04113109.
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