Association of atorvastatin with the risk of hepatotoxicity: a pilot prescription sequence symmetry analysis

PURPOSE: This study aimed to evaluate Atorvastatin (ATO)-associated hepatotoxicity using prescription sequence symmetry analysis (PSSA), based on a health insurance database of a Chinese population living in Jiangsu Province, China. METHODS: Patients prescribed ATO and hepatoprotective drugs in 2017 were identified, and the run-in period was determined based on the “waiting-time” distribution. Adjusted sequence ratio (ASR) and 95% confidence interval (95% CI) were calculated to estimate the risk of ATO-associated hepatotoxicity under different time intervals or based on gender and age stratification. RESULTS: A total of 2,549 patients, with 1,518 filling the ATO prescription first and 1,031 filling the ATO prescription second, were analyzed. After setting the run-in period as 30 days and the time interval as 15, 30, 60, 90, 120, and 180 days, the ASRs were 1.492 (95% CI: 1.367–1.652), 1.399 (95% CI: 1.308–1.508), 1.280 (95% CI: 1.213–1.357), 1.292 (95% CI: 1.234–1.356), 1.278 (95% CI: 1.226–1.336), and 1.274 (95% CI: 1.229–1.323), respectively. No significant difference was observed between different genders and ages (χ(2)=0.161, P=0.688; χ(2)=1.565, P=0.211, respectively). CONCLUSION: This is the first study conducted in a real-world setting to evaluate the relationship between ATO and hepatotoxicity using the PSSA in a Chinese population. We found a 1.3- to 1.5-fold increase in risk of hepatotoxicity following ATO, with the greater risk occurring within the first 30 days of treatment.