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). ISSN 2047-9980

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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.

Item Type:	Article
Uncontrolled Keywords:	inorganic nitrate,nitrite,randomized trial,angina,ischemia,exercise
Faculty \ School:	Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups:	Faculty of Medicine and Health Sciences > Research Groups > Epidemiology and Public Health Faculty of Medicine and Health Sciences > Research Groups > Norwich Clinical Trials Unit Faculty of Medicine and Health Sciences > Research Groups > Health Services and Primary Care Faculty of Medicine and Health Sciences > Research Groups > Public Health and Health Services Research (former - to 2023) Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health Faculty of Science > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Groups > Norwich Epidemiology Centre Faculty of Medicine and Health Sciences > Research Centres > Population Health
Depositing User:	Pure Connector
Date Deposited:	03 Aug 2017 08:17
Last Modified:	24 Oct 2023 00:56
URI:	https://ueaeprints.uea.ac.uk/id/eprint/64337
DOI:	10.1161/JAHA.117.006478

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