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      Statin use and prognosis of lung cancer: a systematic review and meta-analysis of observational studies and randomized controlled trials

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          Previous clinical studies reported inconsistent results on the associations of statins with the mortality and survival of lung cancer patients. This review and meta-analysis summarized the impact of statins on mortality and survival of lung cancer patients.

          Materials and methods

          Eligible papers of this meta-analysis were searched by using PubMed, EMBASE, and Cochrane until July 2017. Primary end points were the mortality (all-cause mortality and cancer-specific mortality) and survival (progression-free survival and overall survival) of patients with statin use. Secondary end points were overall response rate and safety. The random-effects model was used to calculate pooled HRs and 95% CIs.


          Seventeen studies involving 98,445 patients were included in the meta-analysis. In observational studies, the pooled HR indicated that statins potentially decreased the cancer-specific mortality and promoted the overall survival of lung cancer patients. Statins showed an association with decreased all-cause mortality in cohort studies (HR =0.77, 95% CI: 0.59–0.99), but not in case-control studies (HR =0.75, 95% CI: 0.50–1.10). However, statin use showed no impact on mortality and overall survival in randomized controlled trials. Meanwhile, this meta-analysis indicated that statin use did not affect the progression-free survival of lung cancer patients in observational studies and randomized controlled trials. In addition, statins potentially enhanced the effects of tyrosine kinase inhibitors (HR=0.86, 95% CI: 0.76–0.98) and chemotherapy (HR=0.86, 95% CI: 0.81–0.91) on the overall survival of patients with non-small-cell lung cancer, but did not increase overall response rate and toxicity.


          Statins were potentially associated with the decreasing risk of mortality and the improvement of overall survival in observational studies but not in randomized controlled trials.

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          Most cited references 22

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          Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients.

          This study aimed to evaluate the effectiveness of 3-hydroxy-3-methyl-glutaryl-CoA reductase inhibitors (statins) in primary prevention of cardiovascular events. The role of statins is well established for secondary prevention of cardiovascular disease (CVD) clinical events and mortality. Little is known of their role in primary cardiovascular event prevention. We conducted comprehensive searches of 10 electronic databases from inception to May 2008. We contacted study investigators and maintained a comprehensive bibliography of statin studies. We included randomized trials of at least 12-month duration in predominantly primary prevention populations. Two reviewers independently extracted data in duplicate. We performed random-effects meta-analysis and meta-regression, calculated optimal information size, and conducted a mixed-treatment comparison analysis. We included 20 randomized clinical trials. We pooled 19 trials (n = 63,899) for all-cause mortality and found a relative risk (RR) of 0.93 (95% confidence interval [CI]: 0.87 to 0.99, p = 0.03 [I(2) = 5%, 95% CI: 0% to 51%]). Eighteen trials (n = 59,469) assessed cardiovascular deaths (RR: 0.89, 95% CI: 0.81 to 0.98, p = 0.01 [I(2) = 0%, 95% CI: 0% to 41%]). Seventeen trials (n = 53,371) found an RR of 0.85 (95% CI: 0.77 to 0.95, p = 0.004 [I(2) = 61%, 95% CI: 38% to 77%]) for major cardiovascular events, and 17 trials (n = 52,976) assessed myocardial infarctions (RR: 0.77, 95% CI: 0.63 to 0.95, p = 0.01 [I(2) = 59%, 95% CI: 24% to 74%]). Incidence of cancer was not elevated in 10 trials (n = 45,469) (RR: 1.02, 95% CI: 0.94 to 1.11, p = 0.59 [I(2) = 0%, 95% CI: 0% to 46%]), nor was rhabdomyolysis (RR: 0.97, 95% CI: 0.25 to 3.83, p = 0.96 [I(2) = 0%, 95% CI: 0% to 40%]). Our analysis included a sufficient sample to reliably answer our primary outcome of CVD mortality. Statins have a clear role in primary prevention of CVD mortality and major events.
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            Impact of statin use on cancer recurrence and mortality in breast cancer: A systematic review and meta-analysis.

            Statins have shown antineoplastic properties in preclinical studies with breast cancer cells. They inhibit the enzyme "HMG CoA reductase" and the expression of this enzyme in cancer cells has been implicated as a favorable prognostic factor in patients with breast cancer. After a search of MEDLINE and Embase from inception through November 2015, 817 abstracts were reviewed to identify studies that described an association between statin use and outcomes in breast cancer. A total of 14 studies which included 75,684 women were identified. In a meta-analysis of 10 studies, statin use was associated with improved recurrence-free survival (RFS; HR 0.64; 95% CI 0.53-0.79, I(2)  = 44%). Furthermore, this RFS benefit appeared to be confined to use of lipophilic statins (HR 0.72; 95% CI 0.59-0.89) as hydrophilic statin use was not associated with improvement in RFS (HR 0.80; 95% CI 0.44-1.46). Statin users similarly showed improved overall survival in a meta-analysis with substantial heterogeneity (8 studies, HR 0.66; 95% CI 0.44-0.99, I(2)  = 89%). Statin users also had improved cancer-specific survival, although this relationship was measured with less precision (six studies, HR 0.70; 95% CI 0.46-1.06, I(2)  = 86%). In conclusion, breast cancer patients who use statins, or specifically, lipophilic statins show improved recurrence-free survival. Statin users also had improved overall survival and cancer-specific survival. These findings should be assessed in a prospective randomized cohort and the choice of statin, dose and biomarkers that may predict the efficacy of these drugs should be identified.
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              Statin improves survival in patients with EGFR-TKI lung cancer: A nationwide population-based study

              Long-term use of statins has been reported to reduce the risk of death in patients with lung cancer. This study investigated the effect of statin use among patients with lung cancer receiving epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKIs) therapy. A nationwide, population-based case-control study was conducted using the Taiwan National Health Insurance Research Database. From January 1, 1997 to December 31, 2012, a total of 1,707 statin and 6,828 non-statin matched lung cancer cohorts with EGFR-TKIs treatment were studied. Statin use was associated with a reduced risk of death (HR: 0.58, 95% CI: 0.54–0.62, p < 0.001). In addition, statin use was associated with a significantly longer median progression-free survival (8.3 months, 95% CI: 7.6–8.9 vs. 6.1 months, 95% CI: 6.0–6.4, p < 0.001) and median overall survival (35.5 months, 95% CI: 33.8–38.1 vs. 23.9 months, 95% CI: 23.4–24.7, p < 0.001). In conclusion, statins might potentially enhance the therapeutic effect and increase survival in patients with lung cancer receiving EGFR-TKI therapy.

                Author and article information

                Drug Des Devel Ther
                Drug Des Devel Ther
                Drug Design, Development and Therapy
                Drug Design, Development and Therapy
                Dove Medical Press
                23 January 2019
                : 13
                : 405-422
                [1 ]Department of Thoracic Surgery, Yichang Central People’s Hospital, Yichang, PR China
                [2 ]Department of Respiratory Medicine, Respiratory Disease Research Institute of China, Three Gorges University, Yichang, PR China, hxq910813@ 123456163.com
                [3 ]Department of Respiratory Medicine, Yichang Central People’s Hospital, Yichang, PR China, hxq910813@ 123456163.com
                [4 ]Department of Academic Management, Clinical Research Center, Three Gorges University, Yichang, PR China
                Author notes
                Correspondence: Zhi-Gang Hu, Department of Respiratory Medicine, Respiratory Disease Research Institute of China, Three Gorges University, No 183 Yiling Road, Yichang 443003, PR China, Email hxq910813@ 123456163.com

                These authors contributed equally to this work

                © 2019 Xia et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Original Research

                Pharmacology & Pharmaceutical medicine

                prognosis, lung cancer, mortality, survival, statins, statin


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