Association Between Statin Use After Diagnosis of Esophageal Cancer and Survival: A Population-Based Cohort Study

• Published in: Gastroenterology (New York, N.Y. 1943) Vol. 150; no. 4; pp. 854 - 865.e1
• Main Authors: Alexandre, Leo, Clark, Allan B, Bhutta, Hina Y, Chan, Simon S.M, Lewis, Michael P.N, Hart, Andrew R
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.04.2016
• Subjects: Adenocarcinoma - diagnosis; Adenocarcinoma - drug therapy; Adenocarcinoma - mortality; Aged; Aged, 80 and over; Chi-Square Distribution; CPRD; Dose-Response Relationship, Drug; Esophageal Neoplasms - diagnosis; Esophageal Neoplasms - drug therapy; Esophageal Neoplasms - mortality; Esophagus; Female; Gastroenterology and Hepatology; HMG-CoA; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Linear Models; Male; Middle Aged; Multivariate Analysis; Pleiotropy; Proportional Hazards Models; Protective Factors; Registries; Risk Assessment; Risk Factors; Time Factors; Treatment Outcome; United Kingdom - epidemiology; CPRD; general practitioner; esophageal cancer; Office of National Statistics; DDD; esophagogastic junctional adenocarcinoma; HR; interquartile range; ONS; EC; National Cancer Registry; BMI; General Practice Research Database; esophageal squamous cell carcinoma; body mass index; CI; EAC; HMG-CoA; GP; IQR; ESCC; Esophagus; Pleiotropy; defined-daily dose; esophageal adenocarcinoma; hazard ratio; EGJA; confidence interval; GPRD; NCR
• ISSN: 0016-5085; 1528-0012
• DOI: 10.1053/j.gastro.2015.12.039

Background & Aims Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors), commonly prescribed to prevent cardiovascular disease, promote apoptosis and limit proliferation of esophageal cancer cell lines. We investigated whether statin use after a diagnosis of esophageal cancer is associated with reduced esophageal cancer–specific and all-cause mortality. Methods We identified a cohort of 4445 men and women in the United Kingdom diagnosed with esophageal cancer from January 2000 through November 2009 using the General Practice Research Database. The National Cancer Registry and Office of National Statistics data sets established the histologic subtype and cancer-specific mortality, respectively. Cox proportional hazard regression analysis with time-dependent exposures estimated the association between statin use after diagnosis and esophageal cancer–specific and all-cause mortality. Results The median survival time of the entire cohort was 9.2 months (interquartile range [IQR], 3.7–23.2 mo). Among subjects who used statins after a diagnosis of esophageal cancer, the median survival time was 14.9 months (IQR, 7.1–52.3 mo) compared with 8.1 months for nonusers (IQR, 3.3–20 mo). In the entire cohort, statin use after diagnosis was associated with a decreased risk of esophageal cancer–specific mortality (adjusted hazard ratio [HR], 0.62; 95% confidence interval [CI], 0.44–0.86) and all-cause mortality (HR, 0.67; 95% CI, 0.58–0.77). In patients with esophageal adenocarcinoma, statin use after diagnosis was associated with a decreased risk of esophageal cancer–specific mortality (HR, 0.61; 95% CI 0.38–0.96) and all-cause mortality (HR, 0.63; 95% 0.43–0.92). This effect was not observed in patients with esophageal squamous cell carcinoma. There was no evidence for effect modification of these associations with statin use before the cancer diagnosis. Conclusions In a large population-based cohort, statin use after a diagnosis of esophageal adenocarcinoma, but not esophageal squamous cell carcinoma, was associated with reduced esophageal cancer–specific and all-cause mortality.