Elsevier

Pancreatology

Volume 13, Issue 3, May–June 2013, Pages 196-200
Pancreatology

Original article
Prior statin therapy is associated with milder course and better outcome in acute pancreatitis – A cohort study

https://doi.org/10.1016/j.pan.2013.03.008Get rights and content

Abstract

Background

Statin treatment was shown to be associated with improved outcomes in several inflammatory conditions. We wanted to evaluate the effects of statin therapy on the course and outcome of acute pancreatitis (AP).

Methods

A prospective cohort study included patients with acute pancreatitis divided into two groups according to statin use prior to hospitalization. Age, sex, etiology of AP, Ranson's score, APACHE II score and maximal CRP were recorded. Outcome measures were hospital length of stay and mortality. Matching of patients for matched analyses was done using individual matching and propensity score matching using variables a priori associated with course and outcome of acute pancreatitis.

Results

Inclusion criteria were met for 1062 patients of whom 92 were taking statins. Statin users were older and had higher body mass indexes. Severe disease was more common in the no-statin group than in statin group (20.6% vs. 8.7% respectively). All severity markers were also higher in the no-statin group. All cause mortality was not different, while cardiovascular mortality was higher in the statin group in the cohort analysis. After matching by either method, the severity of disease was greater for the patients without statins treatment. Pancreatitis related mortality was higher in the no-statin group after matching. Among patients who developed severe AP, statin users showed lower Ranson's and APACHE II scores and lower maximal CRP.

Conclusions

Prior statin treatment significantly reduces morbidity and mortality in acute pancreatitis. Further studies are needed to evaluate possible therapeutic use of statins in acute pancreatitis.

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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