Inorganic nitrate benefits contrast-induced nephropathy after coronary angiography for acute coronary syndromes: the NITRATE-CIN trial

Author:

Jones Daniel A123ORCID,Beirne Anne-Marie12,Kelham Matthew12,Wynne Lucinda2,Andiapen Mervyn2,Rathod Krishnaraj S12ORCID,Parakaw Tipparat1,Adams Jessica3,Learoyd Annastazia3,Khan Kamran3,Godec Thomas3,Wright Paul4,Antoniou Sotiris4,Wragg Andrew12,Yaqoob Muhammad15,Mathur Anthony12ORCID,Ahluwalia Amrita13ORCID

Affiliation:

1. William Harvey Research Institute, Barts & The London Faculty of Medicine & Dentistry, Queen Mary University of London , Charterhouse Square, London EC1 M 6BQ , UK

2. Barts Interventional Group, Barts Heart Centre, Barts Health NHS Trust , London , UK

3. Barts Cardiovascular Clinical Trials Unit, Queen Mary University of London , Charterhouse Square, London EC1M 6BQ , UK

4. Department of Pharmacy, Barts Heart Centre , Barts Health NHS Trust, London , UK

5. Department of Nephrology , Barts Health NHS Trust, London , UK

Abstract

Abstract Background and Aims Contrast-induced nephropathy (CIN), also known as contrast-associated acute kidney injury (CA-AKI) underlies a significant proportion of the morbidity and mortality following coronary angiographic procedures in high-risk patients and remains a significant unmet need. In pre-clinical studies inorganic nitrate, which is chemically reduced in vivo to nitric oxide, is renoprotective but this observation is yet to be translated clinically. In this study, the efficacy of inorganic nitrate in the prevention of CIN in high-risk patients presenting with acute coronary syndromes (ACS) is reported. Methods NITRATE-CIN is a double-blind, randomized, single-centre, placebo-controlled trial assessing efficacy of inorganic nitrate in CIN prevention in at-risk patients presenting with ACS. Patients were randomized 1:1 to once daily potassium nitrate (12 mmol) or placebo (potassium chloride) capsules for 5 days. The primary endpoint was CIN (KDIGO criteria). Secondary outcomes included kidney function [estimated glomerular filtration rate (eGFR)] at 3 months, rates of procedural myocardial infarction, and major adverse cardiac events (MACE) at 12 months. This study is registered with ClinicalTrials.gov: NCT03627130. Results Over 3 years, 640 patients were randomized with a median follow-up of 1.0 years, 319 received inorganic nitrate with 321 received placebo. The mean age of trial participants was 71.0 years, with 73.3% male and 75.2% Caucasian; 45.9% had diabetes, 56.0% had chronic kidney disease (eGFR <60 mL/min) and the mean Mehran score of the population was 10. Inorganic nitrate treatment significantly reduced CIN rates (9.1%) vs. placebo (30.5%, P < .001). This difference persisted after adjustment for baseline creatinine and diabetes status (odds ratio 0.21, 95% confidence interval 0.13–0.34). Secondary outcomes were improved with inorganic nitrate, with lower rates of procedural myocardial infarction (2.7% vs. 12.5%, P = .003), improved 3-month renal function (between-group change in eGFR 5.17, 95% CI 2.94–7.39) and reduced 1-year MACE (9.1% vs. 18.1%, P = .001) vs. placebo. Conclusions In patients at risk of renal injury undergoing coronary angiography for ACS, a short (5 day) course of once-daily inorganic nitrate reduced CIN, improved kidney outcomes at 3 months, and MACE events at 1 year compared to placebo.

Funder

Heart Research UK

Translational Research

The Barts Charity Cardiovascular Programme

NIHR

Thomas Godec and Kamran Khan

Barts Charity Cardiovascular Programme

Publisher

Oxford University Press (OUP)

Reference41 articles.

1. Contrast-Associated acute kidney injury;Mehran;N Engl J Med,2019

2. Contrast-induced nephropathy following angiography and cardiac interventions;Roger;Heart,2016

3. Contrast-Induced acute kidney injury;McCullough;J Am Coll Cardiol,2016

4. Contrast-Induced acute kidney injury-definitions, epidemiology, and implications;Azzalini;Interv Cardiol Clin,2020

5. Meta-analysis: serum creatinine changes following contrast enhanced CT imaging;Kooiman;Eur J Radiol,2012

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