A five-day course of once-daily inorganic nitrate reduces the risk of a serious complication following a coronary angiogram, in which the dye used causes damage to the kidneys. The treatment was also shown to improve renal outcomes at three months and major adverse cardiac events (MACE) at one year compared to placebo.
The clinical trial, led by Queen Mary University of London and funded by Heart Research UK and published today in European Heart Journal, examined whether ingesting inorganic nitrate (NO3-) which becomes nitrite (NO2-) and then NO in the body – could compensate for the loss of NO in the body and help prevent kidney injury in high-risk patients receiving contrast angiography.
Contrast-induced nephropathy (CIN), also known as contrast associated acute kidney injury (CA-AKI), is an uncommon but serious complication following coronary angiography - a commonly used procedure that allows healthcare professionals to examine the blood supply to the heart. The procedure uses a special dye, visible on x-rays, which is injected into the body. Approximately 250,000 coronary angiograms are carried out in the UK every year.
For older people and those with heart failure, chronic kidney disease (CKD), or diabetes with CKD, incidence of CIN can be as high as 55%. CIN is deemed responsible for a third of all hospital-acquired acute kidney injuries, and can lead to serious consequences including longer hospital stays, increased need for kidney transplants, and higher mortality.
640 patients undergoing angiography for non-ST-elevation Acute Coronary Syndrome (ACS) (NSTE-ACS) at Barts Health NHS Trust took part in the trial, with 319 receiving once daily inorganic nitrate capsules (potassium nitrate) and 321 receiving a placebo capsule (potassium chloride). The study showed that patients receiving inorganic nitrate treatment had significantly reduced CIN rates (9.1%) vs placebo (30.5%), lower rates of procedural myocardial infarction (2.7% vs 12.5%), improved three-month renal function and reduced one-year major adverse cardiac events (MACE) (9.1% vs 18.1%) compared to patients who had received the placebo treatment.
These findings together support the concept of NO replacement in the form of a short five –day simple inorganic nitrate capsule as a potential solution to prevent CIN and improve both cardiovascular and kidney outcomes after ACS.
Professor Amrita Ahluwalia, Director of the Barts Cardiovascular Clinical Trials Unit (CVCTU) in the William Harvey Research Institute, said: “The current gold-standard treatment for blocked coronary arteries is inserting a stent. To do this the cardiologist needs to be able to see where the artery is blocked and that is why it is necessary to use a dye to allow the artery to be clearly seen on the angiogram. This trial suggests that a simple 5-day regime of low-cost inorganic nitrate capsule eliminates the risk of what were, up till now, unavoidable damaging effects. We hope to confirm these findings in a large multi-centre trial in the near future, but the results of Nitrate-CIN give us hope.”
Kate Bratt-Farrar, Chief Executive at Heart Research UK, said: “We are pleased to fund this research led by Prof Ahluwalia, which hopes to make changes to coronary angiogram protocols and reduce the risk of serious complications for patients. This will allow healthcare professionals to conduct safer treatments and improve patient wellbeing for those at high-risk of developing complications.
“It is amazing to see the positive outcome of this breakthrough in cardiac research, which was funded by our Translational Research Programme of grants, aiming to bridge the gap between laboratory-based scientific research and patient care. This study has the potential to save countless lives across the UK.”
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