Dietary nitrate may have a therapeutic role in reducing risks of restenosis following percutaneous coronary intervention (PCI) for stable angina, according to new data from the NITRATE-OCT trial. These findings were reported during a Late-Breaking Trial session Saturday at Cardiovascular Research Technologies (CRT) 2023 in Washington, D.C., by Krishnaraj Rathod, PhD, from St. Bartholomew's Hospital, London, on behalf of the NITRATE-OCT study investigators. Speaking at CRT, Rathod said stable angina remains an area of “significant morbidity,” affecting 1.3 million people in the U.K. and 14.1 million people in the U.S., noting that while PCI can be an effective treatment for stable angina, complications including restenosis and stent thrombosis remain relatively common. Indeed, he noted that studies have estimated the cost of complications after PCI to be around $15 billion in the U.S., leading many to look for options to reduce the risks of such adverse outcomes following PCI. Nitrate study In a previously published protocol for the NITRATE-OCT study, Rathod and colleagues noted that repeat events are thought to be due, in part, to continued enhanced platelet reactivity, endothelial dysfunction and, ultimately, restenosis of the stented artery. They added that in a healthy cardiovascular system, tonically generated nitric oxide (NO), produced via the conventional L-arginine/NO synthesis pathway, plays an essential role in maintaining homeostasis and in sustaining healthy cardiac function, perfusion and cardio-protection. However, in patients with coronary artery disease, generalized endothelial dysfunction is characterized by a deficiency in bioavailable NO, they said, noting that the replacement of this “lost” NO represents an approach that might offer therapeutic utility. “Recently, a simple and safe method has been identified for elevating circulating nitrite levels via inorganic nitrate supplementation through consumption of vegetables (eg, beetroot),” they said, noting that recent studies in healthy volunteers and patients with cardiovascular disease showed that dietary nitrate intake, in the form of beetroot juice, led to dose-dependent rises in circulating nitrite levels and was associated with improvement in endothelial dysfunction. “This is the first randomized-controlled trial assessing the use of dietary nitrate to reduce the rates of restenosis in patients undergoing percutaneous coronary intervention for stable angina,” said the authors, noting that the study will determine the potential of dietary nitrate as adjunctive therapy in patients with stable angina. Design and findings A total of 300 participants were randomized to receive either a nitrate-rich beetroot juice (n = 150) or a nitrate-depleted beetroot juice (n = 150), of whom 208 were followed up at 6 months, 194 were followed up at 1 year, and 190 were followed up at 2 years. At baseline, participants of both arms of the trial were predominantly white, male, and had an average age of 61.59 years. Participants also had similar body mass index scores (28.81 kg/m2 vs 28.95 kg/m2), and similar incidence of diabetes (both 22%), hypertension (73.3% vs 74%), and previous myocardial infarction (36.7% vs 37.3%). Reporting data from the NITRATE-OCT trial at CRT, Rathod noted that the primary endpoint for the study was the assessment of restenosis, made by measurement of in-stent late-loss assessed by quantitative coronary angiography (QCA) at 6 months ± 1 month. Secondary endpoints included assessments of major adverse cardiac events (MACE) at 3, 9, 12 and 24 months, and mechanistic information such as change in flow-mediated dilation, and measuring markers of platelet reactivity, inflammation, and NO pathways. “Once a day oral dietary nitrate for 6 months was well tolerated and safe in patients with stable angina undergoing elective PCI with stent implantation,” said Rathod. Furthermore, he revealed that dietary nitrate resulted in a significant reduction in late lumen loss (LLL) at 6 months, with approximately a 53% reduction in LLL versus the nitrate-depleted placebo arm (stent LLL: 0.117 mm vs 0.244 mm, p = 0.0165; segment LLL: 0.055 mm vs 0.269 mm, p=0.0011). Alongside a reduction in LLL, Rathod reported a trend toward a reduction in 2-year MACE (p = 0.0416). “These results suggest that dietary nitrate may have a therapeutic role in reducing restenosis following PCI for stable angina,” he said, adding that the findings from the study now warrant further investigation in larger clinical trials. Image Credit: Jason Wermers/CRTonline.org