Data from PRESERVE (Prevention of serious adverse events following angiography) indicate that neither intravenous sodium bicarbonate nor acetylcysteine, compared with saline and placebo, reduce the risk of death, need for dialysis, or persistent decline in kidney function in patients at high risk of renal complications who are undergoing angiography. Both treatments are extensively used in clinical practice to reduce the risk of contrast-related kidney injury after angiography.
Writing in The New England Journal of Medicine, Steven Weisbord (Veterans Affairs Pittsburgh Healthcare System, Pittsburgh, USA) and others report: “On the basis of hypotheses that urinary alkalinisation and scavenging of reactive oxygen species mitigate renal tubular epithelial-cell injury from the use of iodinated contrast material, multiple studies have compared intravenous sodium bicarbonate with intravenous sodium chloride and have evaluated treatment with acetylcysteine for the prevention of contrast-associated acute kidney injury”. However, they note that the results from these studies have been “inconsistent” and “consequently equipoise exists regarding these interventions, despite their widespread use in clinical practice”. Therefore, given that most of the previous trials were underpowered, the aim of PRESERVE was to evaluate these treatments in a large population of high-risk patients undergoing coronary or non-coronary angiography.
In the randomised double-blind two by two factorial trial, 4,993 patients were randomised to receive intravenous sodium bicarbonate (2,511) or sodium chloride (2,482) and acetylcysteine (2,495) or placebo (2,498). At baseline, the medium serum creatinine level was 1.5mg per deciliter and the estimated glomerular filtration rate (eGFR) was 50.2ml per minute per 1.73m2. The primary endpoint was a composite of death, the need for dialysis, or a persistent increase of at least 50% from baseline in the serum creatinine level at 90 to 104 days after angiography and confirmed at subsequent testing within 14 days. Secondary endpoints included contrast-associated acute kidney injury.
Of those who underwent angiography (4,937), 90.5% underwent coronary angiography—with 28.5% also undergoing percutaneous coronary intervention—and 9.5% underwent non-coronary angioplasty.
There were no significant differences in the primary endpoint between patients in the sodium bicarbonate and those in the sodium chloride group: 4.4% vs. 4.7% (p=0.62). Nor were the any differences in the primary endpoint between the acetylcysteine group and the placebo group (4.6% vs. 4.5%; p=0.88). Additionally, there were no significant differences in contrast-associated acute kidney injury or the other secondary endpoints between groups in both comparisons.
Weisbord et al note that, unlike their study, previous studies used the endpoint of a small increase in the blood creatinine level occurring within days of contrast administration. They observe that such increases are associated with an increased risk of progressive kidney disease, cardiovascular complications, and death but add that previous studies have not found a decrease in mortality or decreased need for dialysis with reductions in contrast-associated acute kidney injury seen with the use of sodium bicarbonate or of acetylcysteine.
They conclude that “consequently” that their findings “support the strong likelihood” that neither sodium bicarbonate nor acetylcysteine is clinically effective at preventing acute kidney injury or longer term outcomes after angiography. Furthermore, they conclude that based on the findings of the PRESERVE trial, the standard of care for the prevention of contrast-associated acute kidney injury and associated serious adverse events in high-risk patients should be the administration of isotonic intravenous sodium chloride fluid.
Coinciding with its publication in The New England Journal of Medicine, Weisbord presented the results of PRESERVE at the 2017 American Heart Association scientific sessions (11–15 November, Anaheim, USA).