LAUSR

Question In patients at high risk for renal complications after angiography, what are the efficacies of IV sodium bicarbonate vs IV sodium chloride, and acetylcysteine vs placebo, for preventing major adverse outcomes and acute kidney injury (AKI)? Methods Design 2 x 2 factorial, randomized, placebo-controlled trial (Prevention of Serious Adverse Events Following Angiography [PRESERVE] trial). ClinicalTrials.gov NCT01467466. The trial was stopped early for futility. Allocation {Concealed}*. Blinding Blinded (patients, clinicians, and {data collectors}*). Follow-up period 104 days. Setting 53 medical centers in the USA (Veterans Affairs clinics), Australia, Malaysia, and New Zealand. Patients 5177 adults 18 years of age (mean age 70 y, 94% men, 81% had diabetes) who were scheduled for coronary or noncoronary angiography and had an estimated glomerular filtration rate (eGFR) 15 to 44.9 mL/min/1.73 m2 or, for patients with diabetes, eGFR 45 to 59.9 mL/min/1.73 m2. Exclusion criteria included emergency angiography, dialysis, or unstable baseline creatinine level. Interventions IV 1.26% sodium bicarbonate, 150 mmol/L (n =2511), or IV 0.9% sodium chloride, 154 mmol/L (n =2482), administered based on protocol-specific ranges; and oral acetylcysteine, 1200 mg (n =2495) or placebo (n =2498) given 1 hour before and 1 hour after angiography and continued twice daily for 4 days (total 10 doses). A median 85 mL of contrast material was administered. Outcomes Primary outcome was a composite of death, need for dialysis, or 50% persistent increase in serum creatinine level at 90 to 104 days after angiography. Secondary outcomes included contrast-induced AKI. 7860 patients were needed to detect a decrease in the primary outcome from 8.7% to 6.5% with 90% power ( =0.05), assuming 3% loss to follow-up and no interaction between interventions. Patient follow-up 96% (modified intention-to-treat analysis). Main results The main results are in the Table. There was no interaction between sodium bicarbonate and acetylcysteine (P =0.33). Conclusion In patients at high risk for renal complications after angiography, IV sodium bicarbonate did not differ from IV sodium chloride, and acetylcysteine did not differ from placebo for preventing adverse events or contrast-induced acute kidney injury. IV sodium bicarbonate vs IV sodium chloride, and acetylcysteine vs placebo, in high-risk patients having angiography Outcomes Event rates At 104 d Sodium bicarbonate Sodium chloride RRR (95% CI) Primary composite outcome 4.4% 4.7% 7% (21 to 27) RRI (CI) Contrast-induced AKI 9.5% 8.3% 14% (4 to 36) Acetylcysteine Placebo Primary composite outcome** 4.6% 4.5% 2% (21 to 31) Contrast-induced AKI 9.1% 8.7% 5% (12 to 25) AKI = acute kidney injury; other abbreviations defined in Glossary. RRR, RRI, and CI calculated from control event rates and odds ratios in article. Death (RRR 13%, CI 23 to 38), need for dialysis (RRI 9%, CI 35 to 79), or 50% persistent increase in serum creatinine level at 90 to 104 d after angiography (RRI 10%, CI 35 to 89). 25% or 0.5 mg/dL (44 mol/L) increase in serum creatinine level from baseline at 3 to 5 d after angiography. **Death (RRR 10%, CI 22 to 55), need for dialysis (RRR 3%, CI 59 to 42), or 50% persistent increase in serum creatinine level at 90 to 104 d after angiography (RRR 4%, CI 65 to 44). Commentary Contrast-induced AKI is a major contributor to morbidity and mortality, particularly in patients with compromised renal function. Meta-analyses of small trials testing the protective effect of IV sodium bicarbonate and/or oral acetylcysteine have shown heterogeneous results, with no overall clear benefit (1, 2). In the largest and most rigorous trial of these treatments to date, Weisbord and colleagues found no difference in the composite outcome or AKI between groups or prespecified subgroups. Study enrollment was stopped early due to futility (according to prespecified guidelines), which was not unreasonable. However, stopping early, combined with an event rate that was only about half of that anticipated (4.4% to 4.7% observed vs 8.7% expected), resulted in an imprecise treatment estimate for the primary outcome and a 95% CI including as much as a 25% relative risk reduction. (CIs around components of the outcome, such as need for dialysis, were even wider.) The low event rate may have been related to a low rate of hypovolemia and relatively low contrast volumes. The timing and rate of fluid administration were largely determined by individual clinicians. Despite these limitations, in the context of previous studies, this trial shows that acetylcysteine or sodium bicarbonate do not improve outcomes after angiography. Although guidelines recommend IV fluids for prevention of AKI, this is based on poor evidence and may provide no benefit for many high-risk patients receiving contrast (3). The best approach to prevent contrastinduced AKI is to avoid dehydration and renal toxic agents and to minimize contrast exposure.