Long-term statin use and risk of cancers: a target trial emulation study

• Published in: Journal of clinical epidemiology 2024-08, Vol.172, p.111425, Article 111425
• Main Authors: Xu, Wanchun, Chan, Linda, Danaei, Goodarz, Lu, Yuan, Wan, Eric Yuk Fai
• Format: Article
• Language: English
• Subjects: Bias; Cancer; Cancer therapies; Cardiovascular disease; Cholesterol; Clinical trials; Colorectal cancer; Colorectal carcinoma; Comorbidity; Diabetes; Disease prevention; Drug safety; Electronic health records; Electronic medical records; Health risks; Hyperlipidemia; Initiators; Lipids; Lung cancer; Lung carcinoma; Observational studies; Pancreatic cancer; Pancreatic carcinoma; Patients; Prostate cancer; Prostate carcinoma; Real-world evidence; Sex; Statin; Statins; Statistical analysis; Subgroups; Target trial emulation; Urothelial cancer; Urothelial carcinoma
• ISSN: 0895-4356; 1878-5921; 1878-5921
• DOI: 10.1016/j.jclinepi.2024.111425

Controversy exists regarding potential cancer risks associated with long-term statin use. This study aimed to use real-world data to investigate the association between cancer incidence and sustained statin use over a 10-year period. Using territory-wide public electronic medical records in Hong Kong, we emulated a sequence of nested target trials on patients who met indications for statin initiation in each calendar month from January 2009 to December 2011. Statin initiators and noninitiators were matched in a 1:1 ratio to mimic the randomization of eligible person-trials at baseline. Pooled logistic regression was applied to obtain the hazard ratios for the cancer incidence of statin initiation in intention-to-treat analysis, with the adjustment of baseline confounders and the inverse probability weighting accounting for the postbaseline confounders in per-protocol analysis. Among 8,560,051 eligible person-trials, 119,715 noninitiators were matched to 119,715 initiators for analysis. Over the 10-year study period, the estimated hazard ratio of overall cancer incidence was 0.96 (0.87, 1.05), and the standardized 10-year risk difference was −0.4% (−1.3%, 0.4%) in the per-protocol analysis. For the cancer subtypes of interest (ie, breast cancer, colorectal cancer, hematological cancer, pancreatic cancer, prostate cancer, urothelial carcinoma, and lung cancer), the 10-year risk differences ranged from −0.3% to 0.2% in the per-protocol analysis. No observable risk change for cancer was found in all patient subgroups with regards to their sex, age (4), and statin indication. Statin use has no impact on cancer incidence over a 10-year follow-up period, including all cancer subtypes of interest and patient subgroups with regards to sex, age, comorbidities, and statin indications.