El-Refai Sherif M, Brown Joshua D, Arnold Susanne M, Black Esther P, Leggas Markos, Talbert Jeffery C
Sherif M. El-Refai, Susan M. Arnold, Esther P. Black, Markos Leggas, and Jeffery C. Talbert, University of Kentucky, Lexington, KY; and Joshua D. Brown, University of Florida, Gainesville, FL.
JCO Clin Cancer Inform. 2017 Nov;1:1-12. doi: 10.1200/CCI.17.00010.
Cohort studies report associations between statin use and improved survival in patients with cancer. We used pharmacoepidemiologic methods to evaluate the survival of patients with cancer who received statins alone or in ostensibly synergistic drug combinations.
Patients with cancer who were diagnosed from 2010 to 2013 were identified in a large health care claims database. The rate of all-cause death up to 1 year after diagnosis was compared by Cox proportional hazard regression. Sensitivity analyses included age stratification, statin type and intensity, and comparison with or without bisphosphonates and dipyridamole.
Among 312,907 identified patients with cancer, treatment groups included statin users (n = 65,440), nonstatin users who received medications that block cholesterol absorption (n = 9,289), and nonusers (n = 226,007). Statin use before diagnosis was associated with improved overall survival compared with no treatment (hazard ratio [HR], 0.85; 95% CI, 0.80 to 0.91) and specifically in patients with leukemia, lung, or renal cancers. Nonstatin users had increased overall survival compared with no treatment (HR, 0.73; 95% CI, 0.62 to 0.85); when stratified, this difference held true only for pancreatic cancer and leukemia. No differences were observed between statin and nonstatin groups. Bisphosphonate use alone had no effect (n = 4,528), but patients who used both statins and bisphosphonates (n = 4,090) had increased survival compared with no treatment (HR, 0.60; 95% CI, 0.45 to 0.81). The effect of the combination of dipyridamole and statin use (n = 651) was not significant compared with no treatment.
This study suggests that the combination of statins with drugs that affect isoprenylation, such as bisphosphonates, improves survival in patients with cancer. Consideration of pathway-specific pharmacology allows for hypotheses testing with the pharmacoepidemiologic approach. Prospective evaluation of these findings warrants clinical investigation and preclinical mechanistic studies.
队列研究报告了他汀类药物使用与癌症患者生存率提高之间的关联。我们采用药物流行病学方法评估单独使用他汀类药物或使用表面上具有协同作用的药物组合的癌症患者的生存率。
在一个大型医疗保健索赔数据库中识别出2010年至2013年诊断为癌症的患者。通过Cox比例风险回归比较诊断后1年内的全因死亡率。敏感性分析包括年龄分层、他汀类药物类型和强度，以及与使用或不使用双膦酸盐和双嘧达莫的比较。
在312,907名已识别的癌症患者中，治疗组包括他汀类药物使用者（n = 65,440）、接受阻断胆固醇吸收药物的非他汀类药物使用者（n = 9,289）和未使用者（n = 226,007）。与未治疗相比，诊断前使用他汀类药物与总体生存率提高相关（风险比[HR]，0.85；95%可信区间，0.80至0.91），特别是在白血病、肺癌或肾癌患者中。与未治疗相比，非他汀类药物使用者的总体生存率有所提高（HR，0.73；95%可信区间，0.62至0.85）；分层后，这种差异仅在胰腺癌和白血病中成立。他汀类药物组和非他汀类药物组之间未观察到差异。单独使用双膦酸盐没有效果（n = 4,528），但同时使用他汀类药物和双膦酸盐的患者（n = 4,090）与未治疗相比生存率有所提高（HR，0.60；95%可信区间，0.45至0.81）。与未治疗相比，双嘧达莫和他汀类药物联合使用（n = 651）的效果不显著。
本研究表明，他汀类药物与影响异戊二烯化的药物（如双膦酸盐）联合使用可提高癌症患者的生存率。考虑特定途径的药理学允许使用药物流行病学方法进行假设检验。对这些发现进行前瞻性评估值得进行临床研究和临床前机制研究。
