Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.
Institute of Health and Society, University of Oslo, Oslo, Norway.
JAMA Oncol. 2018 Jan 1;4(1):63-70. doi: 10.1001/jamaoncol.2017.2752.
Patients with cancer who use statins appear to have a substantially better survival than nonusers in observational studies. However, this inverse association between statin use and mortality may be due to selection bias and immortal-time bias.
To emulate a randomized trial of statin therapy initiation that is free of selection bias and immortal-time bias.
DESIGN, SETTING, AND PARTICIPANTS: We used observational data on 17 372 patients with cancer from the Surveillance, Epidemiology, and End Results (SEER)-Medicare database (2007-2009) with complete follow-up until 2011. The SEER-Medicare database links 17 US cancer registries and claims files from Medicare and Medicaid in 12 US states. We included individuals with a new diagnosis of colorectal, breast, prostate, or bladder cancer who had not been prescribed statins for at least 6 months before the cancer diagnosis. Individuals were duplicated, and each replicate was assigned to either the strategy "statin therapy initiation within 6 months after diagnosis" or "no statin therapy initiation." Replicates were censored when they stopped following their assigned strategy, and the potential selection bias was adjusted for via inverse-probability weighting. Hazard ratios (HRs), cumulative incidences, and risk differences were calculated for all-cause mortality and cancer-specific mortality. We then compared our estimates with those obtained using the same analytic approaches used in previous observational studies.
Statin therapy initiation within 6 months after cancer diagnosis.
Cancer-specific and all-cause mortality using SEER-Medicare data and data from previous studies.
Of the 17 372 patients whose data were analyzed, 8440 (49%) were men, and 8932 (51%) were women (mean [SD] age, 76.4 [7.4] years; range, 66-115 years). The adjusted HR (95% CI) comparing statin therapy initiation vs no initiation was 1.00 (0.88-1.15) for cancer-specific mortality and 1.07 (0.93-1.21) for overall mortality. Cumulative incidence curves for both groups were almost overlapping (the risk difference never exceeded 0.8%). In contrast, the methods used by prior studies resulted in an inverse association between statin use and mortality (pooled hazard ratio 0.69).
After using methods that are not susceptible to selection bias from prevalent users and to immortal time bias, we found that initiation of therapy with statins within 6 months after cancer diagnosis did not appear to improve 3-year cancer-specific or overall survival.
观察性研究表明，使用他汀类药物的癌症患者的生存情况明显优于未使用者。然而，他汀类药物使用与死亡率之间的这种负相关关系可能归因于选择偏差和无寿命偏差。
模拟他汀类药物治疗起始的随机试验，该试验不受选择偏差和无寿命偏差的影响。
设计、设置和参与者：我们使用来自监测、流行病学和最终结果（SEER）-医疗保险数据库（2007-2009 年）的 17372 名癌症患者的观察性数据，这些患者在癌症诊断前至少 6 个月未接受他汀类药物治疗，并进行了完整的随访，直到 2011 年。SEER-医疗保险数据库链接了美国 17 个癌症登记处和医疗保险和医疗补助在 12 个美国州的索赔文件。我们纳入了新诊断为结直肠癌、乳腺癌、前列腺癌或膀胱癌且在癌症诊断前至少 6 个月未接受他汀类药物治疗的患者。每个个体都被重复，每个副本都被分配到策略“诊断后 6 个月内开始他汀类药物治疗”或“不开始他汀类药物治疗”。当它们停止遵循其指定策略时，副本会被删除，潜在的选择偏差会通过逆概率加权进行调整。使用所有原因死亡率和癌症特异性死亡率计算危险比（HR）、累积发生率和风险差异。然后，我们将我们的估计值与之前观察性研究中使用的相同分析方法的估计值进行了比较。
癌症诊断后 6 个月内开始他汀类药物治疗。
使用 SEER-医疗保险数据和之前研究的数据评估癌症特异性和全因死亡率。
在分析的 17372 名患者中，8440 名（49%）为男性，8932 名（51%）为女性（平均[SD]年龄，76.4[7.4]岁；范围，66-115 岁）。与未开始他汀类药物治疗相比，开始他汀类药物治疗的癌症特异性死亡率调整 HR（95%CI）为 1.00（0.88-1.15），全因死亡率为 1.07（0.93-1.21）。两组的累积发病率曲线几乎重叠（风险差异从未超过 0.8%）。相比之下，之前研究中使用的方法导致他汀类药物使用与死亡率之间呈负相关（汇总危险比 0.69）。
在使用不受现有使用者选择偏差和无寿命偏差影响的方法后，我们发现癌症诊断后 6 个月内开始他汀类药物治疗似乎并不能提高 3 年癌症特异性或总体生存率。
