Mullens Wilfried, Dauw Jeroen, Martens Pieter, Verbrugge Frederik H, Nijst Petra, Meekers Evelyne, Tartaglia Katrien, Chenot Fabien, Moubayed Samer, Dierckx Riet, Blouard Philippe, Troisfontaines Pierre, Derthoo David, Smolders Walter, Bruckers Liesbeth, Droogne Walter, Ter Maaten Jozine M, Damman Kevin, Lassus Johan, Mebazaa Alexandre, Filippatos Gerasimos, Ruschitzka Frank, Dupont Matthias
From Ziekenhuis Oost-Limburg, Genk (W.M., J.D., P.M., P.N., E.M., K.T., M.D.), Hasselt University, Hasselt (W.M., J.D., E.M., L.B.), Universitair Ziekenhuis Brussel and Vrije Universiteit Brussel, Jette (F.H.V.), Grand Hôpital de Charleroi (F.C.) and Centre Hospitalier Universitaire Charleroi (S.M.), Charleroi, OLV Hospital, Aalst (R.D.), Clinique Saint-Luc, Bouge (P.B.), Centre Hospitalier Régional Citadelle Hospital, Liege (P.T.), AZ Groeninge, Kortrijk (D.D.), AZ Klina, Brasschaat (W.S.), and University Hospitals Leuven, Leuven (W.D.) - all in Belgium; the Department of Cardiology, University Medical Center Groningen, University of Groningen, Groningen, the Netherlands (J.M.T.M., K.D.); the Heart and Lung Center, Department of Cardiology, Helsinki University Hospital, and Helsinki University, Helsinki (J.L.); Université Paris Cité, INSERM MASCOT (Cardiovascular Markers in Stressed Conditions), Assistance Publique-Hôpitaux de Paris, Paris (A.M.); the National and Kapodistrian University of Athens and Athens University Hospital Attikon, Athens (G.F.); and Universitäts Spital Zürich, Zurich (F.R.).
N Engl J Med. 2022 Sep 29;387(13):1185-1195. doi: 10.1056/NEJMoa2203094. Epub 2022 Aug 27.
Whether acetazolamide, a carbonic anhydrase inhibitor that reduces proximal tubular sodium reabsorption, can improve the efficiency of loop diuretics, potentially leading to more and faster decongestion in patients with acute decompensated heart failure with volume overload, is unclear.
In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial, we assigned patients with acute decompensated heart failure, clinical signs of volume overload (i.e., edema, pleural effusion, or ascites), and an N-terminal pro-B-type natriuretic peptide level of more than 1000 pg per milliliter or a B-type natriuretic peptide level of more than 250 pg per milliliter to receive either intravenous acetazolamide (500 mg once daily) or placebo added to standardized intravenous loop diuretics (at a dose equivalent to twice the oral maintenance dose). Randomization was stratified according to the left ventricular ejection fraction (≤40% or >40%). The primary end point was successful decongestion, defined as the absence of signs of volume overload, within 3 days after randomization and without an indication for escalation of decongestive therapy. Secondary end points included a composite of death from any cause or rehospitalization for heart failure during 3 months of follow-up. Safety was also assessed.
A total of 519 patients underwent randomization. Successful decongestion occurred in 108 of 256 patients (42.2%) in the acetazolamide group and in 79 of 259 (30.5%) in the placebo group (risk ratio, 1.46; 95% confidence interval [CI], 1.17 to 1.82; P<0.001). Death from any cause or rehospitalization for heart failure occurred in 76 of 256 patients (29.7%) in the acetazolamide group and in 72 of 259 patients (27.8%) in the placebo group (hazard ratio, 1.07; 95% CI, 0.78 to 1.48). Acetazolamide treatment was associated with higher cumulative urine output and natriuresis, findings consistent with better diuretic efficiency. The incidence of worsening kidney function, hypokalemia, hypotension, and adverse events was similar in the two groups.
The addition of acetazolamide to loop diuretic therapy in patients with acute decompensated heart failure resulted in a greater incidence of successful decongestion. (Funded by the Belgian Health Care Knowledge Center; ADVOR ClinicalTrials.gov number, NCT03505788.).
乙酰唑胺是一种碳酸酐酶抑制剂，可减少近端肾小管钠重吸收，它能否提高袢利尿剂的疗效，从而可能使急性失代偿性心力衰竭伴容量超负荷患者实现更快、更多的充血缓解，目前尚不清楚。
在这项多中心、平行组、双盲、随机、安慰剂对照试验中，我们将急性失代偿性心力衰竭、有容量超负荷临床体征（即水肿、胸腔积液或腹水）且N末端B型利钠肽原水平超过1000 pg/ml或B型利钠肽水平超过250 pg/ml的患者随机分组，分别接受添加到标准化静脉袢利尿剂中的静脉注射乙酰唑胺（每日一次，500 mg）或安慰剂（剂量相当于口服维持剂量的两倍）。根据左心室射血分数（≤40%或>40%）进行分层随机分组。主要终点为随机分组后3天内成功实现充血缓解，定义为无容量超负荷体征且无需升级充血治疗。次要终点包括随访3个月内任何原因导致的死亡或因心力衰竭再次住院的复合终点。同时评估安全性。
共有519例患者接受随机分组。乙酰唑胺组256例患者中有108例（42.2%）成功实现充血缓解，安慰剂组259例患者中有79例（30.5%）成功实现充血缓解（风险比，1.46；95%置信区间[CI]，1.17至1.82；P<0.001）。乙酰唑胺组256例患者中有76例（29.7%）因任何原因死亡或因心力衰竭再次住院，安慰剂组259例患者中有72例（27.8%）（风险比，1.07；95%CI，0.78至1.48）。乙酰唑胺治疗使累积尿量和尿钠排泄增加，这一结果与更好的利尿效果一致。两组患者肾功能恶化、低钾血症、低血压及不良事件的发生率相似。
在急性失代偿性心力衰竭患者的袢利尿剂治疗中添加乙酰唑胺可使成功实现充血缓解的发生率更高。（由比利时医疗保健知识中心资助；ADVOR临床试验注册号，NCT03505788。）
