Original articlePrior statin therapy is associated with milder course and better outcome in acute pancreatitis – A cohort study
Introduction
Statins are widely used as cholesterol-lowering agents in primary and secondary prevention of atherosclerotic disease. By inhibiting 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the key enzyme in the synthesis of cholesterol, they decrease cholesterol synthesis; they also cause low-density lipoprotein receptor up-regulation which also lowers serum cholesterol. Statins have been proven to reduce morbidity and mortality in atherosclerotic disease [1].
Besides this main effect, statins have a number of pleiotropic effects, mainly involving inflammatory response. They decrease production of pro-inflammatory cytokines such as tumor necrosis factor alpha (TNF-α), interleukin 1 (IL-1) and interleukin 6 (IL-6) [2]; they increase the release of endothelial nitric oxide (NO) and inhibit inducible NO synthase which can reverse endothelial dysfunction in acute inflammatory response [3]. Statins also have antioxidant, anti-apoptotic and also anti-thrombotic properties [4].
These immunosuppressive and immunomodulatory effects were the reason for several studies that investigated the protective role of statins in severe infections and sepsis. A recent systematic review has included 20 such studies with more than 250,000 pooled patients in the meta-analysis and concluded that statins do demonstrate various protective effects regarding various outcomes, predominantly mortality in sepsis and other severe infections [5].
Acute pancreatitis (AP) is characterized by an inappropriate inflammatory response to the pancreatic tissue damage by activated pancreatic enzymes [6]. About 80% of cases are mild, without systemic consequences. In about 20% of cases the disease takes severe course characterized by pancreatic necrosis and systemic consequences. Cytokine release, reactive oxygen species (ROS), endothelial damage, microcellular thrombosis and other pathogenetic factors are present locally, causing pancreatic necrosis (PN), and systemically, causing systemic inflammatory response syndrome (SIRS) and organ failure, such as acute respiratory distress syndrome, acute renal failure and shock.
Modulation of the inflammatory response in AP should be beneficial, and since statins inhibit all of the above-mentioned mechanisms present in acute pancreatitis, we hypothesized that prior statin use may be associated with better course and outcome of the disease. This study was conducted to test that hypothesis.
Section snippets
Patients and methods
This was a cohort study that prospectively included patients with the primary diagnosis of acute pancreatitis admitted to the Department of Medicine of the University Hospital Centre Zagreb from Jan 2008 to Dec 2011. The aim was to include at least 1000 patients matching the following criteria for AP: clinical presentation consistent with acute pancreatitis (abdominal pain, nausea, vomiting, etc.); more than threefold elevation of serum amylase activity; more than fivefold elevation of urine
Results
During the study period, there were 1154 admissions with acute pancreatitis as the primary diagnosis. Revision of the diagnosis excluded 32 patients who did not fulfill the criteria and 64 patients were excluded due to advanced malignant or chronic disease.
In the remaining cohort of 1062 patients, there were 92 of those who were taking statins for more than two weeks at the time of admission: 13 (14.1%) were taking fluvastatin, 18 (19.6%) simvastatin, 54 (58.7%) atorvastatin and 7 (7.6%)
Discussion
The results of our study show that statin use prior to the occurrence of acute pancreatitis has protective effects. The most obvious illustration of this is the proportion of patients with severe disease in the statin group (8.7%), which is less than half the proportion of severe disease in the no-statin group (20.6%; P = 0.001). Other measures of severity also showed that statin users had less severe pancreatitis than no-statin patients. Statin users were older and had significantly higher
Conflict of interest statement
The authors declare that they have no conflict of interest.
Acknowledgments
We are very grateful to Kathy Rowan from the ICNARC, for the assistance with the matching methods.
Many thanks to Gabriel Borden for proof reading and English corrections in the manuscript.
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2020, PancreatologyCitation Excerpt :Population-based case-control studies have described, on the contrary, that statins are a risk factor for AP [23,24]. Reports addressing the effect of statins on disease severity are heterogeneous, with some studies showing no effect [25,26] and others describing better outcomes [27–29]. To sum-up [11], more robust studies (meta-analysis of randomized trials and population-based cohort studies) suggest a protective effect of statins against incident AP, but data regarding the role of statin use in ameliorating disease severity are conflicting.
Statins decrease the risk of acute pancreatitis after endoscopic ultrasound fine-needle aspiration of pancreatic cysts
2020, Hepatobiliary and Pancreatic Diseases InternationalCitation Excerpt :Furthermore, statin use impairs leukocytes recruitment in the sub-endothelial space through down-regulation of several chemokines such as MCP1, IL-8, and RANTES and inhibition of β2-integrins [9]. According to prospective cohort studies and several meta-analyses [10–14], statins seem to play a protective role against AP; moreover, patients undergoing chronic statin treatment seem to develop milder episodes of AP and even decreased mortality [14]. In a large retrospective cohort study based on data from an integrated health-care system, simvastatin consumption was independently associated with a lower probability of having an episode of AP and similar results were noted for atorvastatin, suggesting a class effect [11].
Chronic use of statins and risk of post-ERCP acute pancreatitis (STARK): Study protocol for an international multicenter prospective cohort study
2018, Digestive and Liver DiseaseCitation Excerpt :3-Hydroxy-3-methyl-glutaryl-coenzyme A (HMG co-A) reductase inhibitors (statins) are effective and commonly used worldwide as a treatment for dyslipidemia [5], and increasing evidence shows that statins also have anti-inflammatory effects [5,6]. Earlier reports suggested a potential association of statins to an increased risk of AP, however, several recent studies have demonstrated that the use of statins may actually be a protective factor against AP [7–11]. A meta-analysis of randomized controlled trials suggested that the use of statins is associated with a lower risk of pancreatitis [9].
Prior statin use and the outcomes in patients with first-attack acute pancreatitis: A retrospective cohort study
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2015, Side Effects of Drugs AnnualCitation Excerpt :Original observational studies and case reports previously provided evidence that statins may cause pancreatitis [29c,30c,31c]. Further studies have not established a causal relationship between statins and pancreatitis; with some evidence pointing towards protective effects and others suggesting causation of pancreatitis [32M,33c,34c]. The evidence remains controversial.