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Inorganic nitrate in angina study: A randomized double-blind placebo-controlled trial

Inorganic nitrate in angina study: A randomized double-blind placebo-controlled trial
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 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.

angina • exercise • inorganic nitrate • ischemia • nitrite • randomized trial
Schwarz, Konstantin
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Singh, Satnam
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Parasuraman, Satish
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Rudd, Amelia
1c474b9f-b088-47bc-bc16-2ca7ab47ffd2
Shepstone, Lee
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Feelisch, Martin
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Minnion, Magdalena
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Ahmad, Shakil
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Madhani, Melanie
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Horowitz, John
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Dawson, Dana
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Frenneaux, Michael P.
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Schwarz, Konstantin
8d53a75f-f87d-48a2-a1a4-6f30389f3369
Singh, Satnam
917d5118-cd5e-46e9-baf1-4ae4bb475988
Parasuraman, Satish
c5169f2c-b05c-42dd-b7c8-6d41d2643a64
Rudd, Amelia
1c474b9f-b088-47bc-bc16-2ca7ab47ffd2
Shepstone, Lee
7ca551e6-b5ca-4984-a5c7-8d6983f23580
Feelisch, Martin
8c1b9965-8614-4e85-b2c6-458a2e17eafd
Minnion, Magdalena
ab23b32b-9f8e-4876-aaf5-99cb6a725a2f
Ahmad, Shakil
56205cc8-6dd9-4287-853b-f8bbe6b118fa
Madhani, Melanie
63a48cca-67b7-41ae-bc79-0f4a166f0750
Horowitz, John
75aea564-0d68-4885-80f7-f5a06f53ed3d
Dawson, Dana
5fe72d81-1839-4c4b-93c6-d59d496f327e
Frenneaux, Michael P.
82824b6d-51f1-4b31-9f7a-5b4746d59833

Schwarz, Konstantin, Singh, Satnam, Parasuraman, Satish, Rudd, Amelia, Shepstone, Lee, Feelisch, Martin, Minnion, Magdalena, Ahmad, Shakil, Madhani, Melanie, Horowitz, John, Dawson, Dana and Frenneaux, Michael P. (2017) Inorganic nitrate in angina study: A randomized double-blind placebo-controlled trial. Journal of the American Heart Association, 6 (9). (doi:10.1161/JAHA.117.006478).

Record type: Article

Abstract

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.

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Accepted/In Press date: 22 June 2017
e-pub ahead of print date: 8 September 2017
Keywords: angina • exercise • inorganic nitrate • ischemia • nitrite • randomized trial

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Local EPrints ID: 415002
URI: https://eprints.soton.ac.uk/id/eprint/415002
PURE UUID: 371fddc5-3a84-4484-8751-08d9d72f092f
ORCID for Martin Feelisch: ORCID iD orcid.org/0000-0003-2320-1158

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Date deposited: 20 Oct 2017 16:31
Last modified: 10 Dec 2019 01:37

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Contributors

Author: Konstantin Schwarz
Author: Satnam Singh
Author: Satish Parasuraman
Author: Amelia Rudd
Author: Lee Shepstone
Author: Martin Feelisch ORCID iD
Author: Magdalena Minnion
Author: Shakil Ahmad
Author: Melanie Madhani
Author: John Horowitz
Author: Dana Dawson
Author: Michael P. Frenneaux

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