Statin Use and Severe Acute Liver Injury Among Patients with Elevated Alanine Aminotransferase

Abstract

Introduction

While serious liver injury among statin users is extremely rare, baseline liver enzyme testing is still recommended prior to initiating therapy. The benefit of such screening should be reevaluated based on empirical evidence. This study compared the risk of severe acute liver injury (SALI) between statin initiators with an elevated ALT (>35U/L) matched to statin initiators with a normal ALT level (≤35U/L). Statin initiators with an elevated ALT were additionally compared against matched non-users.

Methods

The study created cohorts from Optum and MarketScan claims data. Exposed and comparison cohorts were propensity score (PS) matched in each dataset and findings were pooled using meta-analysis. Proportional hazards regression was used to estimate hazard ratios (HRs), and a prespecified non-inferiority margin for SALI was set at a HR of 1.8.

Results

232,889 patients with elevated ALT were PS-matched to 232,889 with normal ALT level. The overall incidence rate of SALI was about 19/100,000 person-years among statin initiators. Statin initiators with elevated ALT had no meaningfully increased risk of SALI compared to those with normal ALT (HR=1.15; 95% CI 0.75 to 1.75). Comparing statin initiators with non-initiators with elevated ALT values equally yielded no increased risk (HR=0.76; 95% CI 0.52 to 1.11).

Conclusion

In this large population-based study, SALI in statin users was rare. Importantly, the results showed no evidence that baseline ALT status is a reliable indicator for an increased risk of severe liver injury among statin initiators.

Keywords:

• statins
• liver injury
• liver failure
• alanine aminotransferase

Disclosure

Santosh K Verma is an employee of and own stock options or equity in Aetion, a software-enabled healthcare analytics company. Joanna Huang is an employee of AstraZeneca, the manufacture of rosuvastatin (a type of studied statins). Howard G. Hutchinson is an employee of AstraZeneca, the manufacture of rosuvastatin (a type of studied statins). Irisdaly Estevez is an employee of Aetion, a software-enabled healthcare analytics company, rapid analytics software used to conduct submitted work. Kammy Kuang worked on the study as an employee of Aetion, a software-enabled healthcare analytics company. Shannon L. Reynolds is an employee of and own stock options or equity in Aetion, a software-enabled healthcare analytics company. Sebastian Schneeweiss is participating in investigator-initiated grants to the Brigham and Women’s Hospital from UCB and Boehringer Ingelheim unrelated to the topic of this study. He is a consultant to Aetion Inc., a software manufacturer of which he owns equity. His interests were declared, reviewed, and approved by the Brigham and Women’s Hospital in accordance with their institutional compliance policies. The authors report no other conflicts of interest in this work.

Additional information

Funding

This work was funded by AstraZeneca.