Are Statins Associated With Reduced Risk of Adhesion-Related Complications After Abdominal Surgery?

Adhesions are the result of intra-abdominal scar tissue that can form after abdominal or pelvic surgery. Despite advances in surgical technique and extensive research devoted to their prevention, adhesions remain the most common cause of small bowel obstructions (SBOs), accounting for 56% of SBOs.1 It is estimated that more than 90% of patients who undergo abdominal or pelvic surgery will develop postoperative adhesions. Additionally, adhesions can cause chronic pain, infertility, and increased complexity of subsequent intra-abdominal operations. Considerable time and effort have been devoted to devising methods to prevent adhesions, from modifications in surgical technique to the development of mechanical barriers or chemical compounds. To date, none of these methods have been proven to eliminate the incidence of adhesion-related complications (ARCs). The development of adhesions after abdominal surgery is mediated by inflammatory pathways involving cyclooxygenase enzymes and other profibrotic cytokines. Although numerous barriers derived from various forms of polysaccharides have shown some success in lowering rates of ARCs, some may be associated with higher risk of surgical site infection.2 Thus, there has been an increased focus on the inflammatory pathway leading to adhesions as a potential target for adhesion prevention. Statins have been used for decades to lower low-density lipid cholesterol by inhibiting 3-hydroxy-3-methylglutaryl coenzyme reductase. Animal and cell studies have demonstrated statins also have anti-inflammatory effects by downregulating proinflammatory cytokines.3 However, the association of statin use with postoperative ARCs in humans has not been studied prior to the article by Scott and colleagues.4 Current innovations in adhesion prevention, ranging from laparoscopic and surgical techniques to adhesion barriers, have been shown to reduce ARCs.2,5 However, these methods may not be applicable to all operative settings, such as emergent surgery or a contaminated surgical field. Pharmacological treatments present another option to prevent adhesions. While new drugs require considerable resources, time, and cost to bring to market, Scott and colleagues4 present a valuable opportunity to consider currently used drugs, such as statins, that are known to target the pathways leading to adhesion formation. Statins have been in use for decades and are among the most prescribed medications in the United States, with 26% of adults older than 40 years old taking a statin to lower cholesterol. By using robust epidemiological methods and large populationrepresentative data sets from 2 countries, the authors4 found that concurrent statin use was associated with a decreased hazard of ARCs and SBOs in patients undergoing abdominal surgery in a dosedependent manner. The authors4 used 2 large population data sets, The Health Improvement Network (THIN) from the United Kingdom and Optum Clinformatics Data Mart (Optum) data set from the United States, to examine the association between preoperative statin use and postoperative ARCs. THIN derives its data from electronic medical records of more than 12 million patients in the United Kingdom from 1995 to 2003, while Optum is an administrative claims data set from among the largest private health insurers in the United States, with 77 million patients enrolled from 2000 to 2016. The authors4 performed a time-to-event analysis with a multivariable Cox regression to compare the time to ARC, as defined by SBO or lysis of adhesions, differentiated on statin use at time of surgery. Propensity score matching was used as a sensitivity analysis to ensure comparison of individuals with similar baseline characteristics. Secondary analyses examined the timing of statin use by categorizing it into + Related article