Stark Project: Statins and Risk of Post-Endoscopic Retrograde Cholangiopancreatography Acute Pancreatitits.

Introduction:

Acute Pancreatitis (AP) is the most frequent complication after ERCP; its incidence is around 3.5-4.5%. Post-ERCP AP (PEAP) is defined as a clinical pancreatitis (new or worsened abdominal pain) with amylase/lipase at least three times the upper limit of normal at more than 24 hours after the procedure, requiring hospital admission or a prolongation of planned admission. It is resulting in increased morbidity of patients undergoing this technique, and an increased in health spending, due to prolonged hospital days and patient needs. In this context, different strategies have been investigated to prevent PEAP, for example rectal NSAIDs (indomethacin or diclofenac 100 mg just before or after procedure) and pancreatic stents.

On the other hand, statins are widely used drugs aimed to lower cholesterol blood levels (the frequency of statin use, may be as high as 50% of men and 36% of women between the ages of 65 years and 74 years in USA). The relationship between statins and AP has been controversial. In the past, it was believed that statins were associated to an increased risk of AP. In Data Sheet of different International Drug Agencies, we can find their mainly indications (hypercholesterolemia, mixed dyslipidaemias, hereditary hypercholesterolemia) and commons adverse effects with reference to acute pancreatitis (myopathy, rhabdomyolysis, hepatitis/jaundice, acute pancreatitis...). Besides, some studies, most of them case series or case reports, have associated the use of different statins with drugs induced AP.

However, recent evidence suggests the opposite: Statins could reduce the risk of AP. In a retrospective longitudinal cohort study on data from a big health database from California (USA), with a big population of three millions nine thousand people, the incidence of AP among subjects who used simvastatin was significantly lower than who didn´t use it (0,80 (0,80-0,81)/100.000 consumers/day versus 1,28 (1,27-1,28) /100.000 no consumers/day; crude incidence rate ratio for risk of AP with simvastatin use 0.626 (95% confidence interval (CI) 0.588-0.668, p<0.0001). In this study patients who received simvastatin were more likely to have gallstone-related disorders, alcohol dependence or hyper-triglyceridemia compared with the reference population; nevertheless, risk of AP was significantly reduced with simvastatin use. In multivariate analysis, simvastatin was independently associated with reduced risk of pancreatitis, adjusted RR 0.29 (95%CI 0.27-0.31) after adjusting for age, gender, race/ethnicity, gallstone disorders, alcohol dependence, smoking and hypertriglyceridemia. Similar results were noted with atorvastatin. In a Meta-analysis of 21 randomized controlled trials investigating effects of lipid-modifying therapies on cardiovascular events, was assessed the relationship between lipid modifying therapies and risk of AP. In this study it was concluded that the use of statin therapies was associated with a lower risk of AP, RR 0.79 (95%CI 0.65-0.95; p=0.01). In a case-control study from Denmark, it was examined if statins use is associated with increase risk of acute pancreatitis. 2576 first-time admitted cases of AP were controlled with 25 817 gender-matched controls from the general population. Prescriptions for statins prior to admission with acute pancreatitis or index date among controls were retrieved from prescription databases. Its findings speak against a strong causative effect of statins on the risk of acute pancreatitis, and speculated about it could indicate a mild protective effect.

Some studies even speculate about an improvement in the severity of AP among patients with prior use of statins. In a prospective cohort study from Croatia, which included patients with acute pancreatitis divided into two groups according to statin use prior to hospitalization, severe disease was more common in the no-statin group than in statin group (20.6% vs. 8.7% p=0.001), and severity markers were also higher in the no-statin group.