Lipid-modifying therapies and risk of pancreatitis: a meta-analysis.
BACKGROUND
Statin therapy has been associated with pancreatitis in observational studies. Although lipid guidelines recommend fibrate therapy to reduce pancreatitis risk in persons with hypertriglyceridemia, fibrates may lead to the development of gallstones, a risk factor for pancreatitis.


OBJECTIVE
To investigate associations between statin or fibrate therapy and incident pancreatitis in large randomized trials.


METHODS
Relevant trials were identified in literature searches of MEDLINE, EMBASE, and Web of Science (January 1, 1994, for statin trials and January 1, 1972, for fibrate trials, through June 9, 2012). Published pancreatitis data were tabulated where available (6 trials). Unpublished data were obtained from investigators (22 trials).


METHODS
We included randomized controlled cardiovascular end-point trials investigating effects of statin therapy or fibrate therapy. Studies with more than 1000 participants followed up for more than 1 year were included.


METHODS
Trial-specific data described numbers of participants developing pancreatitis and change in triglyceride levels at 1 year. Trial-specific risk ratios (RRs) were calculated and combined using random-effects model meta-analysis. Between-study heterogeneity was assessed using the I2 statistic.


RESULTS
In 16 placebo- and standard care-controlled statin trials with 113,800 participants conducted over a weighted mean follow-up of 4.1 (SD, 1.5) years, 309 participants developed pancreatitis (134 assigned to statin, 175 assigned to control) (RR, 0.77 [95% CI, 0.62-0.97; P = .03; I2 = 0%]). In 5 dose-comparison statin trials with 39,614 participants conducted over 4.8 (SD, 1.7) years, 156 participants developed pancreatitis (70 assigned to intensive dose, 86 assigned to moderate dose) (RR, 0.82 [95% CI, 0.59-1.12; P = .21; I2 = 0%]). Combined results for all 21 statin trials provided RR 0.79 (95% CI, 0.65-0.95; P = .01; I2 = 0%). In 7 fibrate trials with 40,162 participants conducted over 5.3 (SD, 0.5) years, 144 participants developed pancreatitis (84 assigned to fibrate therapy, 60 assigned to placebo) (RR, 1.39 [95% CI, 1.00-1.95; P = .053; I2 = 0%]).


CONCLUSIONS
In a pooled analysis of randomized trial data, use of statin therapy was associated with a lower risk of pancreatitis in patients with normal or mildly elevated triglyceride levels.
BHF Glasgow Cardiovascular Research Centre, University of Glasgow, 126 University Pl, Glasgow G12 8TA, United Kingdom. david.preiss@glasgow.ac.uk
David
D
Preiss
Matti J
MJ
Tikkanen
Paul
P
Welsh
Ian
I
Ford
Laura C
LC
Lovato
Marshall B
MB
Elam
John C
JC
LaRosa
David A
DA
DeMicco
Helen M
HM
Colhoun
Ilan
I
Goldenberg
Michael J
MJ
Murphy
Thomas M
TM
MacDonald
Terje R
TR
Pedersen
Anthony C
AC
Keech
Paul M
PM
Ridker
John
J
Kjekshus
Naveed
N
Sattar
John J V
JJ
McMurray
D058607:Fibric Acids / Q000009:adverse effects* / Q000627:therapeutic use; D042882:Gallstones / Q000139:chemically induced / Q000150:complications; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects* / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000188:drug therapy; D015228:Hypertriglyceridemia / Q000150:complications / Q000188:drug therapy; D015994:Incidence; D010195:Pancreatitis / Q000139:chemically induced* / Q000453:epidemiology / Q000517:prevention & control*; D016032:Randomized Controlled Trials as Topic; D012306:Risk; D014280:Triglycerides / Q000097:blood
D058607:Fibric Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D014280:Triglycerides