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. 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),

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.

Publication DOI: https://doi.org/10.1161/JAHA.117.006478
Divisions: Aston Medical School
Life & Health Sciences > Biosciences
Life & Health Sciences
Additional Information: Copyright: 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 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. Funding: Medical Research Council, (UK) grant number G1001536.
Uncontrolled Keywords: Angina,Exercise,Inorganic nitrate,Ischemia,Nitrite,Randomized trial,Cardiology and Cardiovascular Medicine
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2017-09-08
Authors: Schwarz, Konstantin
Singh, Satnam
Parasuraman, Satish K.
Rudd, Amelia
Shepstone, Lee
Feelisch, Martin
Minnion, Magdalena
Ahmad, Shakil ( 0000-0002-9294-0475)
Madhani, Melanie
Horowitz, John
Dawson, Dana K.
Frenneaux, Michael P.

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