JAMA:低分子肝素联合胰岛素治疗高甘油三酯血症性急性胰腺炎：一项随机临床试验

Abstract

Importance: Although insulin is widely used for early lipid lowering in hypertriglyceridemic acute pancreatitis, the clinical benefit of heparin combined with insulin remains unclear.

重要性：尽管胰岛素被广泛用于高甘油三酯血症性急性胰腺炎的早期降脂治疗，但肝素联合胰岛素的临床益处仍不明确。

Objective: To examine whether low-molecular-weight heparin (LMWH) combined with insulin is superior to insulin alone in improving clinical outcomes in hypertriglyceridemic acute pancreatitis.

目的：探讨低分子肝素（LMWH）联合胰岛素在改善高甘油三酯血症性急性胰腺炎患者临床结局方面是否优于单用胰岛素。

Design, setting, and participants: This multicenter, open-label, parallel-group, superiority randomized clinical trial was conducted from September 21, 2019, to April 2, 2023, across 13 tertiary hospitals in China. The duration of follow-up was 30 days after randomization. Patients aged 18 to 85 years were eligible if they met the diagnostic criteria for acute pancreatitis, presented with baseline serum triglyceride levels between 1000 and 3550 mg/dL, and were admitted within 48 hours of symptom onset.

设计、场所与参与者：本项多中心、开放标签、平行组、优效性随机临床试验于2019年9月21日至2023年4月2日在中国13家三级医院开展，随访时间为随机分组后30天。纳入年龄18至85岁、符合急性胰腺炎诊断标准、基线血清甘油三酯水平在1000–3550 mg/dL之间且在症状出现48小时内入院的患者。

Interventions: Participants received either subcutaneous LMWH (4000 IU every 12 hours for 3 days) plus insulin (LMWH plus insulin group) or insulin alone (insulin group).

干预措施：受试者分别接受皮下注射低分子肝素（4000 IU，每12小时一次，连续3天）联合胰岛素（LMWH+胰岛素组），或仅接受胰岛素治疗（胰岛素组）。

Main outcomes and measures: The primary end point was a composite of new-onset organ failure (defined as organ failure occurring after randomization but absent during the 24-hour prerandomization period) and/or all-cause mortality within 30 days after randomization.

主要结局指标：主要终点为随机分组后30天内新发器官衰竭（定义为随机分组后出现但在随机分组前24小时未出现的器官衰竭）和/或全因死亡组成的复合事件。

Results: Among 533 randomized patients (median [IQR] age, 39 [33-46] years; 406 [76.2%] male), 264 were randomized to LMWH plus insulin and 269 to insulin alone. The primary end point occurred in 66 (25.0%) of the LMWH and insulin group vs 76 (28.3%) of the insulin group (relative risk [RR], 0.89; 95% CI, 0.67-1.17; P = .40). Both groups achieved the triglyceride target (<500 mg/dL) in a median (IQR) of 2 (1-3) days (P = .94). Safety outcomes were similar between groups, including new-onset bleeding events (RR, 0.61; 95% CI, 0.15-2.53; P = .73), triglyceride rebound (RR, 0.53; 95% CI, 0.28-1.01; P = .05), and drug-related adverse events (RR, 0.79; 95% CI, 0.30-2.10; P = .64).

结果：在533名随机分组患者中（中位[IQR]年龄39[33–46]岁；男性406人[76.2%]），264人进入LMWH+胰岛素组，269人进入胰岛素组。主要终点发生率在LMWH+胰岛素组为66例（25.0%），胰岛素组为76例（28.3%）（相对风险[RR] 0.89；95%置信区间[CI] 0.67–1.17；P=0.40）。两组达到甘油三酯目标值（<500 mg/dL）的中位时间均为2天（IQR 1–3天）（P=0.94）。安全性结局两组相似，包括新发出血事件（RR 0.61；95% CI 0.15–2.53；P=0.73）、甘油三酯反弹（RR 0.53；95% CI 0.28–1.01；P=0.05）以及药物相关不良事件（RR 0.79；95% CI 0.30–2.10；P=0.64）。

Conclusions and relevance: In this randomized clinical trial, the combination of LMWH and insulin failed to demonstrate superior efficacy vs insulin alone in patients with hypertriglyceridemic acute pancreatitis. LMWH might not be necessary for early lipid-lowering in hypertriglyceridemic acute pancreatitis.

结论与相关性：在这项随机临床试验中，低分子肝素联合胰岛素未能显示出比单用胰岛素更优的疗效。对于高甘油三酯血症性急性胰腺炎的早期降脂治疗，可能无需使用低分子肝素。