From the Veterans Affairs (VA) Pittsburgh Healthcare System and University of Pittsburgh School of Medicine, Pittsburgh (S.D.W., P.M.P.); University of Sydney (M.G.) and the George Institute for Global Health, University of New South Wales (M.G., A.C.), Sydney, and the Menzies School of Health Research, Darwin, NT (A.C.) - all in Australia; Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston (H.J.); Minneapolis VA Health Care System and University of Minnesota, Minneapolis (S.G., E.O.M.); VA Cooperative Studies Program Coordinating Center (S.S.T., M.B., R.F., H.W., M.A., J.M., J.K.) and the Cardiology Section (D.L.B.), VA Boston Healthcare System, and Brigham and Women's Hospital Heart and Vascular Center, Harvard Medical School (D.L.B.) - all in Boston; VA Cooperative Studies Program Pharmacy Coordinating Center, Albuquerque, NM (T.A.C.); Stanford University Department of Medicine, Palo Alto (G.M.C.), and San Francisco VA Medical Center and University of California, San Francisco, San Francisco (K.S.) - all in California; and the VA Connecticut Healthcare System and Program of Applied Translational Research, Yale University, New Haven (C.R.P.).
N Engl J Med. 2018 Feb 15;378(7):603-614. doi: 10.1056/NEJMoa1710933. Epub 2017 Nov 12.
Intravenous sodium bicarbonate and oral acetylcysteine are widely used to prevent acute kidney injury and associated adverse outcomes after angiography without definitive evidence of their efficacy.
Using a 2-by-2 factorial design, we randomly assigned 5177 patients at high risk for renal complications who were scheduled for angiography to receive intravenous 1.26% sodium bicarbonate or intravenous 0.9% sodium chloride and 5 days of oral acetylcysteine or oral placebo; of these patients, 4993 were included in the modified intention-to-treat analysis. The primary end point 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 days. Contrast-associated acute kidney injury was a secondary end point.
The sponsor stopped the trial after a prespecified interim analysis. There was no interaction between sodium bicarbonate and acetylcysteine with respect to the primary end point (P=0.33). The primary end point occurred in 110 of 2511 patients (4.4%) in the sodium bicarbonate group as compared with 116 of 2482 (4.7%) in the sodium chloride group (odds ratio, 0.93; 95% confidence interval [CI], 0.72 to 1.22; P=0.62) and in 114 of 2495 patients (4.6%) in the acetylcysteine group as compared with 112 of 2498 (4.5%) in the placebo group (odds ratio, 1.02; 95% CI, 0.78 to 1.33; P=0.88). There were no significant between-group differences in the rates of contrast-associated acute kidney injury.
Among patients at high risk for renal complications who were undergoing angiography, there was no benefit of intravenous sodium bicarbonate over intravenous sodium chloride or of oral acetylcysteine over placebo for the prevention of death, need for dialysis, or persistent decline in kidney function at 90 days or for the prevention of contrast-associated acute kidney injury. (Funded by the U.S. Department of Veterans Affairs Office of Research and Development and the National Health and Medical Research Council of Australia; PRESERVE ClinicalTrials.gov number, NCT01467466 .).
静脉注射碳酸氢钠和口服乙酰半胱氨酸被广泛用于预防血管造影后急性肾损伤和相关不良结局，但没有明确证据表明它们有效。
我们采用 2×2 析因设计，将 5177 名有发生肾并发症风险的患者随机分配，接受静脉注射 1.26%碳酸氢钠或静脉注射 0.9%氯化钠和 5 天的口服乙酰半胱氨酸或口服安慰剂；其中 4993 名患者纳入改良意向治疗分析。主要终点是 90 天时死亡、需要透析或血清肌酐水平比基线至少升高 50%的复合终点。造影剂相关急性肾损伤是次要终点。
在预设的中期分析后，赞助商停止了试验。碳酸氢钠和乙酰半胱氨酸在主要终点方面没有相互作用（P=0.33）。碳酸氢钠组 2511 例患者中有 110 例（4.4%）发生主要终点，而氯化钠组 2482 例患者中有 116 例（4.7%）（比值比，0.93；95%置信区间[CI]，0.72 至 1.22；P=0.62）；乙酰半胱氨酸组 2495 例患者中有 114 例（4.6%）发生主要终点，而安慰剂组 2498 例患者中有 112 例（4.5%）（比值比，1.02；95%CI，0.78 至 1.33；P=0.88）。两组之间造影剂相关急性肾损伤的发生率无显著差异。
在接受血管造影的有发生肾并发症风险的患者中，与静脉注射氯化钠相比，静脉注射碳酸氢钠或与安慰剂相比，口服乙酰半胱氨酸对预防 90 天时的死亡、需要透析或肾功能持续下降没有益处，也不能预防造影剂相关急性肾损伤。（由美国退伍军人事务部研究与发展办公室和澳大利亚国家卫生与医学研究委员会资助；PRESERVE 临床试验。gov 编号，NCT01467466）。
