The Association Between Statin Use After Diagnosis and Mortality Risk in Patients With Esophageal Cancer: A Retrospective Cohort Study of United States Veterans

Objective: Statins may reduce mortality from esophageal cancer by both reducing incidence but also improving prognosis. However, prior studies of statin use and mortality have reported conflicting results. Methods: We identified 7882 patients with esophageal adenocarcinoma (EAC) and 3868 with esophageal squamous cell carcinoma (ESCC) from the VA Central Cancer Registry diagnosed between 2002 and 2016. We identified prescriptions for statins that were filled before and after cancer diagnosis. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% CIs for mortality risk. We used a time-varying exposure to avoid immortal-time bias and a 3 month lag (following patients from 3 months after cancer diagnosis) to reduce reverse causation. A sensitivity analysis was conducted varying the lag duration between date of cancer diagnosis and start of follow-up. Results: Statin use after diagnosis was recorded in 27.4% of EAC and 17.1% of ESCC patients. In EAC patients, statin use after diagnosis was associated with a decreased risk of cancer specific (HR, 0.79; 95% CI 0.70–0.88) and all-cause mortality (HR, 0.80; 95% CI 0.74–0.86). Similarly, statin use after diagnosis of ESCC was associated with a decreased risk of cancer specific (HR, 0.77; 95% CI 0.63–0.92) and all-cause mortality (HR, 0.83; 95% CI 0.74–0.95). The inverse associations were attenuated towards the null with a 6-month lag. Conclusions: Post-diagnosis statin use was associated with reduced mortality in esophageal cancer patients; however, the effect may be partially due to reverse causality as patients with poor prognosis are unlikely to initiate statin therapy.