他汀类药物和胆固醇对胰腺癌患者死亡率的影响。

Influence of Statins and Cholesterol on Mortality Among Patients With Pancreatic Cancer.

机构信息

Affiliations of authors: Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena, CA (BZH, AHX); Department of Internal Medicine, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (JIC), and Division of Gastroenterology, Center for Pancreatic Care, Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA (BUW), Kaiser Permanente Los Angeles Medical Center, Los Angeles, CA; Department of Epidemiology, UCLA Fielding School of Public Health, Los Angeles, CA (BZH); David Geffen School of Medicine at UCLA, Los Angeles, CA (EL).

出版信息

J Natl Cancer Inst. 2016 Dec 31;109(5). doi: 10.1093/jnci/djw275. Print 2017 May.

DOI:10.1093/jnci/djw275

PMID:28040693

Abstract

BACKGROUND

Recent studies have suggested associations between statins and enhanced survival among patients with pancreatic ductal adenocarcinoma (PDAC). However, the relationship between statins, cholesterol, and survival remains unclear.

METHODS

We conducted a retrospective cohort study on 2142 PDAC patients in a regional integrated healthcare system from 2006 to 2014. Electronic pharmacy records were used to abstract information on the type, length, and dosage of statin exposures starting in the year prior to diagnosis. The cumulative and individual effects of simvastatin, lovastatin, atorvastatin, pravastatin, and rosuvastatin on mortality were assessed using Cox proportional hazards regression. Statins were evaluated as any use (pre- and postdiagnosis as a time-dependent variable) and baseline use (prediagnosis only). We also evaluated whether low-density lipoprotein (LDL) cholesterol, measured at various time windows prior to diagnosis, had an independent influence on survival. Additional analyses were performed to examine whether cholesterol mediated the relationship between statins and mortality. All models included age, race, stage, surgery, gemcitabine-based chemotherapy, and the Charlson comorbidity index as covariates.

RESULTS

Any (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.79 to 0.97) and baseline (HR = 0.88, 95% CI = 0.79 to 0.98) statin use were both associated with a decreased risk in mortality. When assessing individual statins, we found reduced mortality among simvastatin (HR = 0.87, 95% CI = 0.77 to 0.98) and atorvastatin (HR = 0.58, 95% CI = 0.46 to 0.72) users. Cholesterol was not associated with mortality and did not mediate any relationships between statins and survival.

CONCLUSIONS

Statin use rather than cholesterol level was associated with lower mortality risk in patients with pancreatic cancer. Statins appear to improve survival through a lipid-independent mechanism.

摘要

背景

最近的研究表明，他汀类药物与胰腺导管腺癌（PDAC）患者的生存改善有关。然而，他汀类药物、胆固醇与生存之间的关系仍不清楚。

方法

我们对 2006 年至 2014 年期间在一个区域综合医疗系统中的 2142 例 PDAC 患者进行了回顾性队列研究。电子病历记录用于提取他汀类药物暴露的类型、长度和剂量信息，起始时间为诊断前一年。使用 Cox 比例风险回归评估辛伐他汀、洛伐他汀、阿托伐他汀、普伐他汀和瑞舒伐他汀对死亡率的累积和个体影响。他汀类药物评估为任意使用（诊断前和诊断后作为时间依赖性变量）和基线使用（仅诊断前）。我们还评估了在诊断前的不同时间窗口测量的低密度脂蛋白（LDL）胆固醇是否对生存有独立影响。进行了额外的分析，以检查胆固醇是否介导了他汀类药物与死亡率之间的关系。所有模型均包含年龄、种族、分期、手术、吉西他滨为基础的化疗和 Charlson 合并症指数作为协变量。

结果

任意（风险比[HR] = 0.87，95%置信区间[CI] = 0.79 至 0.97）和基线（HR = 0.88，95% CI = 0.79 至 0.98）使用他汀类药物均与死亡率降低相关。在评估单个他汀类药物时，我们发现辛伐他汀（HR = 0.87，95% CI = 0.77 至 0.98）和阿托伐他汀（HR = 0.58，95% CI = 0.46 至 0.72）使用者的死亡率降低。胆固醇与死亡率无关，也不能介导他汀类药物与生存之间的任何关系。