Division of Gastroenterology and Hepatology, University of Colorado Anschutz Medical Campus, Aurora.
Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania, Philadelphia.
JAMA Netw Open. 2021 Feb 1;4(2):e2036315. doi: 10.1001/jamanetworkopen.2020.36315.
Adhesion-related complications (ARCs), including small-bowel obstruction, are common complications of intra-abdominal surgery. Statins, which have antifibrotic pleiotropic effects, inhibit adhesion formation in murine models but have not been assessed in humans.
To assess whether statin use at the time of intra-abdominal surgery is associated with a reduction in ARCs.
DESIGN, SETTING, AND PARTICIPANTS: These 2 separate retrospective cohort studies (The Health Improvement Network [THIN] and Optum's Clinformatics Data Mart [Optum]) compared adults receiving statins with those not receiving statins at the time of intra-abdominal surgery. Individuals undergoing intra-abdominal surgery from January 1, 1996, to December 31, 2013, in the United Kingdom and from January 1, 2000, to December 31, 2016, in the US were included in the study. Those with obstructive events before surgery or a history of inflammatory bowel disease were excluded. Data analysis was performed from September 1, 2012, to November 24, 2020.
The primary exposure was statin use at the time of surgery.
The primary outcome was ARCs, defined as small-bowel obstruction or need for adhesiolysis, occurring after surgery. Sensitivity analyses included statin use preceding but not concurrent with surgery, fibrate use, and angiotensin-converting enzyme inhibitor use. All analyses were adjusted for age, sex, and conditions associated with microvascular disease, such as hypertension, hyperlipidemia, obesity, and tobacco use; surgical approach and site; and diagnosis of a malignant tumor.
A total of 148 601 individuals met the inclusion criteria for THIN (mean [SD] age, 49.6 [17.7] years; 70.1% female) and 1 188 217 for Optum (mean [SD] age, 48.2 [16.4] years; 72.6% female). A total of 2060 participants (1.4%) experienced an ARC in THIN and 54 136 (4.6%) in Optum. Statin use at the time of surgery was associated with decreased risk of ARCs (THIN: adjusted hazard ratio [HR], 0.81; 95% CI, 0.71-0.92; Optum: adjusted HR, 0.92; 95% CI, 0.90-0.95). Similar associations were appreciated between statins and small-bowel obstruction (THIN: adjusted HR, 0.80; 95% CI, 0.70-0.92; Optum: adjusted HR, 0.88; 95% CI, 0.85-0.91).
This study's findings suggest that, among individuals in 2 separate cohorts undergoing intra-abdominal surgery, statin use may be associated with a reduced risk of postoperative ARCs. Statins may represent an inexpensive, well-tolerated pharmacologic option for preventing ARCs.
粘连相关并发症（ARCs），包括小肠梗阻，是腹部手术的常见并发症。他汀类药物具有抗纤维化的多效作用，可抑制鼠类模型中的粘连形成，但尚未在人类中进行评估。
评估腹部手术时使用他汀类药物是否与 ARC 减少相关。
设计、设置和参与者：这两项独立的回顾性队列研究（健康改进网络[THIN]和 Optum 的 Clinformatics Data Mart [Optum]）比较了接受他汀类药物治疗和未接受他汀类药物治疗的腹部手术患者。研究纳入了 1996 年 1 月 1 日至 2013 年 12 月 31 日期间在英国和 2000 年 1 月 1 日至 2016 年 12 月 31 日期间在美国接受腹部手术的成年人。排除了手术前有阻塞性事件或炎症性肠病病史的患者。数据分析于 2012 年 9 月 1 日至 2020 年 11 月 24 日进行。
主要暴露是手术时使用他汀类药物。
主要结局是手术后发生的 ARC，定义为小肠梗阻或需要粘连松解。敏感性分析包括他汀类药物在手术前但不与手术同时使用、使用贝特类药物和使用血管紧张素转换酶抑制剂。所有分析均调整了年龄、性别和与微血管疾病相关的疾病，如高血压、高脂血症、肥胖和吸烟；手术方法和部位；以及恶性肿瘤的诊断。
THIN 共纳入 148601 名符合条件的患者（平均[SD]年龄，49.6[17.7]岁；70.1%为女性），Optum 共纳入 1188217 名患者（平均[SD]年龄，48.2[16.4]岁；72.6%为女性）。THIN 中有 2060 名患者（1.4%）发生 ARC，Optum 中有 54136 名患者（4.6%）发生 ARC。手术时使用他汀类药物与 ARC 风险降低相关（THIN：调整后的危险比[HR]，0.81；95%CI，0.71-0.92；Optum：调整后的 HR，0.92；95%CI，0.90-0.95）。他汀类药物与小肠梗阻之间也存在类似的关联（THIN：调整后的 HR，0.80；95%CI，0.70-0.92；Optum：调整后的 HR，0.88；95%CI，0.85-0.91）。
本研究结果表明，在 2 个独立队列中接受腹部手术的个体中，他汀类药物的使用可能与术后 ARC 风险降低相关。他汀类药物可能是一种廉价、耐受性良好的预防 ARC 的药物选择。
