Inorganic Nitrate in Angina Study: A Randomized Double‐Blind Placebo‐Controlled Trial

Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease

Shakil Ahmad¹  Amelia Rudd¹  Martin Feelisch¹  Satnam Singh¹  Michael P. Frenneaux²  Melanie Madhani³  Satish K. Parasuraman⁴  Konstantin Schwarz⁴  Lee Shepstone⁴  Magdalena Minnion⁴  John Horowitz⁵  Dana K. Dawson⁵ 

[1] Dentistry, University of Aberdeen, Aberdeen, UK;Aston Medical Research Institute, Aston University, Birmingham, UK;Norwich Medical School, University of East Anglia, Norwich, UK;;School of Medicine &University of Southampton, Southampton, UK;

关键词: angina;    exercise;    inorganic nitrate;    ischemia;    nitrite;    randomized trial;   

DOI  :  10.1161/JAHA.117.006478

来源: DOAJ

【 摘 要 】

BackgroundIn 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 ResultsSeventy 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. ConclusionsSodium nitrate treatment may confer a modest exercise capacity benefit in patients with chronic angina who are taking other background medication. Clinical Trial RegistrationURL: https://www.clinicaltrials.gov/. Unique identifier: NCT02078921. EudraCT number: 2012‐000196‐17.

【 授权许可】

Unknown