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Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial
BACKGROUND: In this double‐blind randomized placebo‐controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. METHODS AND RESULTS: Seventy patients with stable angina, positive electroca...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634294/ https://www.ncbi.nlm.nih.gov/pubmed/28887315 http://dx.doi.org/10.1161/JAHA.117.006478 |
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author | Schwarz, Konstantin Singh, Satnam Parasuraman, Satish K. Rudd, Amelia Shepstone, Lee Feelisch, Martin Minnion, Magdalena Ahmad, Shakil Madhani, Melanie Horowitz, John Dawson, Dana K. Frenneaux, Michael P. |
author_facet | Schwarz, Konstantin Singh, Satnam Parasuraman, Satish K. Rudd, Amelia Shepstone, Lee Feelisch, Martin Minnion, Magdalena Ahmad, Shakil Madhani, Melanie Horowitz, John Dawson, Dana K. Frenneaux, Michael P. |
author_sort | Schwarz, Konstantin |
collection | PubMed |
description | BACKGROUND: In this double‐blind randomized placebo‐controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. METHODS AND RESULTS: Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2‐week washout period before crossing over to the other treatment (n=34 placebo‐nitrate, n=36 nitrate‐placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P=0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P=0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P<0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P=0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. CONCLUSIONS: Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012‐000196‐17. |
format | Online Article Text |
id | pubmed-5634294 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-56342942017-10-18 Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial Schwarz, Konstantin Singh, Satnam Parasuraman, Satish K. Rudd, Amelia Shepstone, Lee Feelisch, Martin Minnion, Magdalena Ahmad, Shakil Madhani, Melanie Horowitz, John Dawson, Dana K. Frenneaux, Michael P. J Am Heart Assoc Original Research BACKGROUND: In this double‐blind randomized placebo‐controlled crossover trial, we investigated whether oral sodium nitrate, when added to existing background medication, reduces exertional ischemia in patients with angina. METHODS AND RESULTS: Seventy patients with stable angina, positive electrocardiogram treadmill test, and either angiographic or functional test evidence of significant ischemic heart disease were randomized to receive oral treatment with either placebo or sodium nitrate (600 mg; 7 mmol) for 7 to 10 days, followed by a 2‐week washout period before crossing over to the other treatment (n=34 placebo‐nitrate, n=36 nitrate‐placebo). At baseline and at the end of each treatment, patients underwent modified Bruce electrocardiogram treadmill test, modified Seattle Questionnaire, and subgroups were investigated with dobutamine stress, echocardiogram, and blood tests. The primary outcome was time to 1 mm ST depression on electrocardiogram treadmill test. Compared with placebo, inorganic nitrate treatment tended to increase the primary outcome exercise time to 1 mm ST segment depression (645.6 [603.1, 688.0] seconds versus 661.2 [6183, 704.0] seconds, P=0.10) and significantly increased total exercise time (744.4 [702.4, 786.4] seconds versus 760.9 [719.5, 802.2] seconds, P=0.04; mean [95% confidence interval]). Nitrate treatment robustly increased plasma nitrate (18.3 [15.2, 21.5] versus 297.6 [218.4, 376.8] μmol/L, P<0.0001) and almost doubled circulating nitrite concentrations (346 [285, 405] versus 552 [398, 706] nmol/L, P=0.003; placebo versus nitrate treatment). Other secondary outcomes were not significantly altered by the intervention. Patients on antacid medication appeared to benefit less from nitrate supplementation. CONCLUSIONS: Sodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012‐000196‐17. John Wiley and Sons Inc. 2017-09-08 /pmc/articles/PMC5634294/ /pubmed/28887315 http://dx.doi.org/10.1161/JAHA.117.006478 Text en © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Original Research Schwarz, Konstantin Singh, Satnam Parasuraman, Satish K. Rudd, Amelia Shepstone, Lee Feelisch, Martin Minnion, Magdalena Ahmad, Shakil Madhani, Melanie Horowitz, John Dawson, Dana K. Frenneaux, Michael P. Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial |
title | Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial |
title_full | Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial |
title_fullStr | Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial |
title_full_unstemmed | Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial |
title_short | Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial |
title_sort | inorganic nitrate in angina study: a randomized double‐blind placebo‐controlled trial |
topic | Original Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5634294/ https://www.ncbi.nlm.nih.gov/pubmed/28887315 http://dx.doi.org/10.1161/JAHA.117.006478 |
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