Inorganic nitrate strongly reduces CIN in high-risk patients undergoing angiography

Dietary inorganic nitrate significantly reduced contrast-induced nephropathy (CIN) in patients at risk for renal injury undergoing coronary angiography for acute coronary syndrome (ACS). Moreover, long-term renal and cardiovascular outcomes in the NITRATE-CIN trial were in favour of patients treated with inorganic nitrate as compared with placebo.

“Older patients with heart failure, chronic kidney disease, or diabetes undergoing angiography for ACS have an increased risk for CIN, a condition that potentially has severe consequences,” said Dr Dan Jones (Queen Mary University of London, UK) [1]. “Although the pathophysiology of CIN is not perfectly understood, it is known that the loss of nitric oxide plays an important role. Replacing this lost nitric oxide may therefore reduce the risk for CIN in these patients.”

The current double-blind, single-centre, phase 2 NITRATE-CIN trial (NCT03627130) enrolled 640 patients undergoing invasive coronary angiography for non-ST elevated ACS who were at risk for CIN. The study population had a mean age of 71.0 years, 26% of the participants were women, 46% had diabetes, 56% had chronic kidney disease with an eGFR <60 mL/min, and the mean Mehran score was 10. They were randomised 1:1 to a 5-day intervention with potassium nitrate (12 mmol/744 mg nitrate) or a placebo. The primary endpoint was the incidence of CIN as defined by the KDIGO criteria [2].

After a median follow-up of 12 months, CIN was observed in 30.5% of the participants in the placebo arm and 9.1% in the inorganic nitrate arm (P<0.0001) [1]. These results were consistent across troponin levels, Mehran risk scores, and diabetic status. However, participants who received prior organic nitrate (n=72) appeared to benefit less from the intervention than those who had not received prior organic nitrate (n=484; OR 0.65 vs OR 0.17; P_interaction=0.04).

Procedural myocardial infarction, a secondary endpoint, occurred in 12.5% and 4.1% of the participants in the placebo arm and inorganic nitrate arm, respectively (P=0.003). Furthermore, Dr Jones mentioned that renal outcomes at 3 months, major adverse cardiovascular events (MACE) at 1 year, and major adverse kidney events (MAKE) at 1 year all favoured participants in the inorganic nitrate arm over those in the placebo arm.

“These results could have important implications for the reduction of the burden of CIN worldwide,” according to Dr Jones. “However, studies powered for MACE and MAKE outcomes should be conducted to confirm these findings.”

1. 
   
   1. Jones DA, et al. The effect of inorganic nitrate on contrast-induced nephropathy in patients undergoing coronary angiography/percutaneous coronary intervention for acute coronary syndrome (ACS). Hot Line Session 8, ESC Congress 2023, 25–28 August, Amsterdam, the Netherlands.
   2. Fliser D, et al. Nephrol Dial Transplant. 2012;27(12):4263–4273.

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Posted on 30 October 2023