Funded in part by Fukuda Denshi
A randomised, factorial trial to reduce arterial stiffness independently of blood pressure: Proof of concept? The VaSera trial testing dietary nitrate and spironolactone
Mills CE, Govoni V, Faconti L, Casagrande ML, Morant SV, Crickmore H, Iqbal F, Maskell P, Masani A, Nanino E, Webb AJ, Cruickshank JK
British journal of clinical pharmacology · 26 citations
Review labels
Neutral facts our review recorded about how this study was done. They describe method, never whether we like the result.
How it was studied
- Design
- Randomized controlled trial (indexed by PubMed)
- Studied in
- People
- Main outcome
- Health markers and function
- Intake measured by
- Not stated
Who paid for it
- Funding
- Industry funded
- Government
- National Institute for Health and Care Research
- Nonprofit
- British Heart Foundation
- University or hospital
- King's College London
- Company
- Fukuda Denshi
Based on 4 listed funder(s).
Publication
- Published
- 2019-12-13 · Br J Clin Pharmacol · vol. 86 · issue 5 · pp. 891–902
- Publisher
- Wiley
- Cited
- 39 citations · more than 92% of similar papers · 2.7× the field average
- Impact
- Top 10% most cited in its field
- References
- 54 works
- Access
- Free to read
- Research areas
- Cardiovascular Health and Disease Prevention · Nitric Oxide and Endothelin Effects · Blood Pressure and Hypertension Studies
- Keywords
- Doxazosin, Blood pressure, Spironolactone, Arterial stiffness, Placebo, Cardiology, Internal medicine, Medicine, Heart failure
- MeSH
- humans, beta vulgaris, diabetes mellitus, type 2, nitrates, spironolactone, double-blind method, blood pressure, dietary supplements, adult, aged, middle aged, female, male, vascular stiffness, pulse wave analysis
12 authors
From GB, FR, BE
- Charlotte Elizabeth MillsSt Thomas' Hospital; King's College London; Guy's and St Thomas' NHS Foundation Trust; Unité de Nutrition Humaine; King's College School; Nutrition Sciences (Belgium); University of Reading
- V. GovoniSt Thomas' Hospital; King's College London; Guy's and St Thomas' NHS Foundation Trust; King's College School
- Luca FacontiSt Thomas' Hospital; King's College London; Guy's and St Thomas' NHS Foundation Trust; British Heart Foundation
- M. CasagrandeSt Thomas' Hospital; King's College London; Guy's and St Thomas' NHS Foundation Trust; King's College School
- S. V. MorantUniversity of Dundee
- Hannah CrickmoreKing's College London; King's College School
Abstract
Aims
To test if spironolactone or dietary nitrate from beetroot juice could reduce arterial stiffness as aortic pulse wave velocity (PWVart), a potential treatment target, independently of blood pressure.
Methods
Daily spironolactone (≤50 mg) vs doxazosin (control ≤16 mg) and 70 mL beetroot juice (Beet-It ≤11 mmol nitrate) vs nitrate-depleted juice (placebo; 0 mmol nitrate) were tested in people at risk or with type-2 diabetes using a double-blind, 6-month factorial trial. Vascular indices (baseline, 12, 24 weeks) were cardiac-ankle vascular index (CAVI), a nominally pressure-independent stiffness measure (primary outcome), PWVart secondary, central systolic pressure and augmentation. Analysis was intention-to-treat, adjusted for systolic pressure differences between trial arms.
Results
Spironolactone did not reduce stiffness, with evidence for reduced CAVI on doxazosin rather than spironolactone (mean difference [95% confidence interval]; 0.25 [-0.3, 0.5] units, P = .080), firmer for PWVart (0.37 [0.01, 0.7] m/s, P = .045). There was no difference in systolic pressure reduction between spironolactone and doxazosin (0.7 [-4.8, 3.3] mmHg, P = .7). Circulating nitrate and nitrite increased on active vs placebo juice, with central systolic pressure lowered -2.6 [-4.5, - 0.8] mmHg, P = .007 more on the active juice, but did not reduce CAVI, PWVart or peripheral pressure. Change in nitrate and nitrite concentrations were 1.5-fold [1.1-2.2] and 2.2-fold [1.3, 3.6] higher on spironolactone than on doxazosin respectively; both P < .05.
Conclusion
Contrary to our hypothesis, in at-risk/type 2 diabetes patients, spironolactone did not reduce arterial stiffness, rather PWVart was lower on doxazosin. Dietary nitrate elevated plasma nitrite, selectively lowering central systolic pressure, observed previously for nitrite.
Abstract via Europe PMC. Copyright remains with the authors or publisher.
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