Previous studies on statins’ effect on survival of patients with pancreatic ductal adenocarcinoma (PDAC) report conflicting results.
To evaluate the association between statin use and PDAC patients’ survival.
A systematic review and meta-analysis was performed including case-control, cohort studies and randomized controlled trials assessing the association between statin use and survival in PDAC patients. Pooled HRs with 95%CIs were calculated using random effects model; publication bias was assessed through Begg and Mazumdar test and heterogeneity by I2 value.
14 studies with 33,137 PDAC patients, 40% under statins, were included. Statins use was associated to a reduced death risk (HR 0.871; 95%CI: 0.819; 0.927; p = 0.0001) suggesting a protective effect, homogeneous for different geographic areas. This effect was significant in surgically resected patients (HR 0.50; 95%CI: 0.32; 0.76; p = 0.001) but not in those with advanced disease (HR 0.78; 95%CI: 0.59; 1.02; p = 0.07). In studies providing information on statin type, only rosuvastatin resulted associated to a reduced risk of death (HR 0.88; 95%CI: 0.81; 0.96; p = 0.004).
Statins use is significantly associated with a reduced risk of death in resected PDAC patients. This finding has to be considered with caution due to publication bias and the availability of only few studies for sensitivity analyses.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Digestive and Liver Disease
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- Cancer statistics, 2013.CA Cancer J Clin. 2013; 63: 11-30
- Projecting cancer incidence and deaths to 2030: the unexpected burden of thyroid, liver, and pancreas cancers in the United States.Cancer Res. 2014; 74: 2913-2921
- Advances in the surgical management of pancreatic cancer.Cancer J. 2001; 7: 312-323
- State of the art and future directions of pancreatic ductal adenocarcinoma therapy.Pharmacol Ther. 2015; 155: 80-104
- Results of surveillance in individuals at high-risk of pancreatic cancer: a systematic review and meta-analysis.United Eur Gastroenterol J. 2018; 6: 489-499
- The association between use of statin or aspirin and pancreatic ductal adenocarcinoma: a nested case-control study in a Korean nationwide cohort.Cancer Med. 2019; 21
- Exclusive and combined use of statins and aspirin and the risk of pancreatic cancer: a case-control study.Sci Rep. 2017; 12: 13-24
- Approach to statin use in 2016: an update.Curr Atheroscler Rep. 2016; 18: 20
- Statin use and its impact on survival in pancreatic cancer patients.Medicine (Baltimore). 2016; 95: e3607
- Statin use is associated to a reduced risk of pancreatic cancer: a meta-analysis.Dig Liver Dis. 2019; 51: 28-37
- Statin use and reduced cancer-related mortality.N Engl J Med. 2012; 367: 1792-1802
- Beyond aspirin-cancer prevention with statins, metformin and bisphosphonates.Nat Rev Clin Oncol. 2013; 10: 625-642
- Impact of statin use on survival in patients undergoing resection for early-stage pancreatic cancer.Am J Gastroenterol. 2015; 110: 1233-1239
- The association of statin use after cancer diagnosis with survival in pancreatic cancer patients: a SEER-medicare analysis.PLoS One. 2015; 10e0121783
- Differential and joint effects of metformin and statins on overall survival of elderly patients with pancreatic adenocarcinoma: a large population-based study.Cancer Epidemiol Biomarkers Prev. 2017; 26: 1225-1232
- The Newcastle-Ottawa Scale (NOS) forassessing the quality of nonrandomised studies in meta-analyses.2014www.ohri.ca/programs/clinicalepidemiology/oxford.asp
- The Cochrane Collaboration’s toolfor assessing risk of bias in randomized trials.BMJ. 2011; 343: d5928
- Meta-analysis in clinical trials.Control Clin Trials. 1986; 7: 177-188
- Quantifying heterogeneity in a meta-analysis.StatMed. 2002; 21: 1539-1558
- Bias in meta-analysis detected bya simple, graphical test.BMJ. 1997; 315: 629-634
- Preferred reporting items for system-atic review and meta-analysis protocols (PRISMA-P) 2015: elaboration andexplanation.BMJ. 2015; 350: g7647
- Metaanalysis of observational studies inepidemiology: a proposal for reporting: metaanalysis of observational studiesin epidemiology (MOOSE) group.JAMA. 2000; 283: 2008-2012
- Statin use shows increased overall survival in patients diagnosed with pancreatic cancer: a meta-analysis.Pancreas. 2019; 48: e22-e23
- Effect of metformin and statin use on survival in pancreatic cancer patients: a systematic literature review and meta-analysis.Curr Med Chem. 2018; 25: 2595-2607
- Pre-diagnosis use of statins associates with increased survival times of patients with pancreatic cancer.Clin Gastroenterol Hepatol. 2018; 16 (1300–1306.e3)
- Statin treatment and outcomes of metastatic pancreatic cancer: a pooled analysis of two phase III studies.Clin Transl Oncol. 2019; 21: 810-816
- Targeting tumor metabolism with statins during treatment for advanced-stage pancreatic cancer.Am J Clin Oncol. 2018; ([Epub ahead of print])https://doi.org/10.1097/COC.0000000000000433
- Impact of concurrent medication use on pancreatic cancer survival-SEER-medicare analysis.Am J Clin Oncol. 2018; 41: 766-771
- Influence of statins and cholesterol on mortality among patients with pancreatic cancer.J Natl Cancer Inst. 2016; 31 (109(5))
- Concomitant statin use has a favorable effect on gemcitabine-erlotinib combination chemotherapy for advanced pancreatic cancer.Yonsei Med J. 2016; 57: 1124-1130
- Statin and metformin use prolongs survival in patients with resectable pancreatic cancer.Pancreas. 2016; 45: 64-70
- Randomized double-blinded, placebo-controlled phase II trial of simvastatin and gemcitabine in advanced pancreatic cancer patients.Cancer Chemother Pharmacol. 2014; 73: 125-130
- Clinical outcomes of chemotherapy for diabetic and nondiabetic patients with pancreatic cancer: better prognosis with statin use in diabetic patients.Pancreas. 2013; 42: 202-208
- Risk of cause-specific death in individuals with cancer-modifying role diabetes, statins and metformin.Int J Cancer. 2017; 15: 2437-2449
- Targeting the metabolic response to statin-mediated oxidative stress produces a synergistic anti-tumor response.Cancer Res. 2019; 27 (pii: canres.0644.2019)
- Evidence-based complementary treatment of pancreatic cancer: a review of adjunct therapies including paricalcitol, hydroxychloroquine, intravenous vitamin C, statins, metformin, curcumin, and aspirin.Cancer Manag Res. 2018; 13: 2003-2018
- Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe.Pancreatology. 2019; 19: 97-104
- Statin therapy in the treatment of active cancer: a systematic review and meta-analysis of randomized controlled trials.PLoS One. 2018; 20: 13
- Effect of statins as a secondary chemopreventive agent among individuals with non-muscle-invasive bladder cancer: a population-based analysis.Urol Oncol. 2017; 35: 342-348
- The relationship between pancreatic cancer and hypercoagulability: a comprehensive review on epidemiological and biological issues.Br J Cancer. 2019; 121: 359-371
- Pro-apoptotic effect of fluvastatin on humansmooth muscle cells.Eur J Pharmacol. 1999; 370: 201-3.47
- 3-Hydroxy-3-methylglutaryl coen-zyme a reductase and isoprenylation inhibitors induce apoptosis of vascular smooth muscle cells in culture.Circ Res. 1998; 83: 490-500
- Differences in antitumor effects of various statins on human pancreatic cancer.Int J Cancer. 2008; 122: 1214-1221
Published online: February 27, 2020
Accepted: January 23, 2020
Received: November 26, 2019
© 2020 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.