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

Figures & data

Table 1 Hepatoprotective drugs included in the atorvastatin analyses

Therapeutic class	Hepatoprotective drugs
Anti-inflammatory agents	Magnesium Isoglycyrrhizinate, Diammonium glycyrrhizinate
Antioxidant agents	Bicyclol, Bifendate
Antidote agents	Reduced glutathione sodium for injection
Choleretic agents	Ademetionine 1,4-Buta nedisulfonate, Ursodeoxycholic acid
Cell membrane repair agent	Polyene phosphatidylcholine

Figure 1 Waiting-time distributions for patients of atorvastatin and hepatoprotective drugs during the period January 2017 to December 2017.

Figure 2 A flow chart of patients’ inclusion and exclusion.

Figure 3 Frequency distribution of patients by days before or after atorvastatin initiation within 180 days.

Table 2 Results from the atorvastatin analysis, by different characteristics

Characteristics	Study population (N)	“Causal” group (n)	“Noncausal” group (n)	CSR	NESR	ASR (95%CI)
Time interval (days)
≤15	277	166	111	1.495	1.002	1.492 (1.367–1.652)
≤30	527	309	218	1.417	1.013	1.399 (1.308–1.508)
≤60	931	528	403	1.310	1.023	1.280 (1.213–1.357)
≤90	1276	731	545	1.341	1.038	1.292 (1.234–1.356)
≤120	1541	888	653	1.360	1.064	1.278 (1.226–1.336)
≤180	1972	1159	813	1.426	1.119	1.274 (1.229–1.323)
Gender*,^†
Male	477	276	201	1.373	1.040	1.320 (1.228–1.430)
Female	454	252	202	1.248	1.003	1.243 (1.150–1.354)
Age (years)*,^‡
<60	430	249	181	1.376	0.979	1.405 (1.303–1.529)
≥60	501	279	222	1.257	1.058	1.188 (1.104–1.289)

Notes: *Setting the time interval as ≤60 days. ^†Comparison between groups, χ²=0.161, P=0.688. ^‡Comparison between groups, χ²=1.565, P=0.211.

Abbreviations: CSR, crude sequence ratio; NESR, null effect sequence ratio; ASR, adjusted sequence ratio; 95% CI, 95% confidence interval.