Heart failure & cardiomyopathiesRandomised controlled trial
Modest Contribution of Bradykinin to Blood Pressure Reduction by Sacubitril/Valsartan in Chronic Heart Failure
- randomized, double-blind crossover trial
Authors' conclusion
BP 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.
Study context
- Population
- Stable ambulatory patients with heart failure and reduced ejection fraction <50% receiving sacubitril/valsartann=36 at acute initiation, n=30 after 8 weeks of chronic therapy · acute initiation 36 · after 8 weeks of chronic therapy 30
- Comparison
- icatibant vs placebo
- Primary endpoint
- Maximal change in mean arterial pressure (MAP)
- Follow-up
- 6 hours after sacubitril/valsartan dosing; acute and after 8 weeks
Primary result
As reported in the abstract
P = 0.013
- First dose of sacubitril/valsartan (50 mg) lowered mean arterial pressure (MAP) by a mean maximum of, similar during icatibant and placebo
- ≈10 mm Hg
Further findings
Natriuretic peptides and urine cGMP after first dose · within 6 hours after the first dose
- Plasma ANP (1-28) and urine cGMP/creatinine increased significantly; B-type NP (1-32) and NT-proBNP did not
- Icatibant partially blunted the rise in urine cGMP/creatinine, but did not affect other parameters
Baseline parameters after chronic therapy · 8 weeks
- Baseline ANP (1-28) remained increased; baseline MAP and NT-proBNP decreased compared with before initiation
Renal hemodynamics after chronic dosing · 8 weeks
- Icatibant decreased renal plasma flow and increased renal vascular resistance, without affecting heart rate, urine volume, urine sodium, cGMP/creatinine, or natriuretic peptides
Original publication
Summarised from the published abstract; every number is checked against it