<p>Association of atorvastatin with the risk of hepatotoxicity: a pilot prescription sequence symmetry analysis</p>

Abstract

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.

Risk of Liver Injury Associated with Intravenous Lipid Emulsions: A Prescription Sequence Symmetry Analysis

“…Drug-induced liver injury accounts for approximately 20% of inpatients with acute liver injury in China, owing to a wide use of traditional Chinese medicine and anti-tuberculosis drugs ( Li et al, 2007 ; Yu et al, 2017 ; Fang et al, 2016 ; Zhang et al, 2019 ). The marker drugs used in both studies, and also in our study, were recommended by the Chinese Medical Association guidelines for the treatment of DILI ( Yu et al, 2017 ), and they were widely used to treat liver injury in clinical practice ( Fang et al, 2016 ; Zhang et al, 2019 ). However, as a signal detection method, PSSA is vulnerable to bias and confounding existing in real-world data ( Davies et al, 2019 ).…”

“…The index drugs in our study are LEs, consisting of S-LEs, alternative-Les, and FO-LEs ( Table 1 ). The marker drugs are a group of hepatic protectors widely used in China with high specificity as the surrogate of liver injury, chosen by literature search, guideline recommendation, and clinical experience (expert consultation) ( Fang et al, 2016 ; Yu et al, 2017 ; Zhang et al, 2019 ), including anti-inflammatory agents, antioxidant agents, antidote agent, choleretics, cell membrane repair agents, and others ( Table 1 ).…”

“…Prescription sequence symmetry analysis (PSSA) is a valid method used for rapid signal detection of adverse drug events (ADE) by calculating the sequence ratio between exposure and outcomes ( Hallas, 1996 ; Tsiropoulos et al, 2009 ), which inherently controls time-constant confounders. For now, only two Chinese studies reported drug-related liver injury using PSSA ( Fang et al, 2016 ; Zhang et al, 2019 ). Moreover, the health insurance data is an important source used for safety evaluation ( Tyree et al, 2006 ).…”

High‐throughput screening for prescribing cascades among real world statin initiators

“…Cardiovascular‐related prescribing cascades are considered high priority targets for deprescribing 9 . To date, seven statin‐related prescribing cascades have been described (Table S1 in the supplement) 10–17 . However, many of these cascades reflect known adverse events observed in large clinical trials or from spontaneous adverse event reporting and thus may have been expected.…”

Cholangiolytic Changes in Statin-Induced Liver Injury

“…Common side effects associated with statin therapy include arthralgia, myalgia, dyspepsia, weakness, and headache. In early clinical trials, elevations of liver enzymes were observed in up to 2% of patients; however, clinically apparent liver injury was rarely observed [1][2][3][4][5][6][7]. In the majority of cases, these mild elevations in liver enzymes were not clinically significant and rarely required discontinuation of therapy [8,9].…”