Statin use and the risk of Clostridium difficile infection: a systematic review with meta-analysis

Abstract

Purpose: Statins have pleiotropic effects beyond cholesterol lowering by immune modulation. The association of statins with primary Clostridium difficile infection (CDI) is unclear as studies have reported conflicting findings. We performed a systematic review and meta-analysis to evaluate the association between statin use and CDI.

Patients and methods: We searched MEDLINE, Embase, and Web of Science from January 1978 to December 2016 for studies assessing the association between statin use and CDI. The Newcastle-Ottawa Scale was used to assess the methodologic quality of included studies. Weighted summary estimates were calculated using generalized inverse variance with random-effects model.

Results: Eight studies (6 case-control and 2 cohort) were included in the meta-analysis, which comprised 156,722 patients exposed to statins and 356,185 controls, with 34,849 total cases of CDI available in 7 studies. The rate of CDI in patients with statin use was 4.3%, compared with 7.8% in patients without statin use. An overall meta-analysis of 8 studies using the random-effects model demonstrated that statins may be associated with a decreased risk of CDI (maximally adjusted odds ratio [OR], 0.80; 95% CI, 0.66-0.97; P=0.02). There was significant heterogeneity among the studies, with an I² of 79%. No publication bias was seen. Meta-analysis of studies that adjusted for confounders revealed no protective effect of statins (adjusted OR, 0.84; 95% CI, 0.70-1.01; P=0.06, I²=75%). However, a meta-analysis of only full-text studies using the random-effects model demonstrated a decreased risk of CDI with the use of statins (OR 0.77; 95% CI, 0.61-0.99; P=0.04, I²=85%).

Conclusion: Meta-analyses of existing studies suggest that patients prescribed a statin may be at decreased risk for CDI. The results must be interpreted with caution given the significant heterogeneity and lack of benefit on analysis of studies that adjusted for confounders.

Keywords: Clostridium difficile infection; incidence; meta-analysis; statins.

Figure 1

Flow diagram of study selection process. Abbreviation: CDI, Clostridium difficile infection.

Figure 2

Analysis of all 8 included studies. (A) Forest plot demonstrating decreased odds of Clostridium difficile infection with statin medications by the random-effects model. (B) Funnel plot demonstrating no evidence of publication bias. Abbreviations: OR, odds ratio; SE, standard error.

Figure 3

Analysis of studies that adjusted for potential confounders. Forest plot demonstrating no protective effect of statins on the risk of CDI. Abbreviation: CDI, Clostridium difficile infection; SE, standard error.

Figure 4

Analysis of full-text studies only. Forest plot demonstrating decreased risk of CDI with use of statins. Abbreviation: CDI, Clostridium difficile infection; SE, standard error.

Figure 5

Analysis of moderate- to high-quality studies. Forest plot demonstrating a decreased risk of CDI with use of statins. Abbreviation: CDI, Clostridium difficile infection; SE, standard error.

Figure 6

Analysis of studies with inpatients only. Forest plot demonstrating a decreased risk of statins on the risk of CDI. Abbreviation: CDI, Clostridium difficile infection; SE, standard error.

Figure 7

Other analyses. (A) Forest plot of 2 studies demonstrating no effect of statins on the recurrence of CDI. (B) Forest plot of 2 studies demonstrating no effect of statins on 30-day CDI mortality. Abbreviation: CDI, Clostridium difficile infection M-H, Mantel-Haenszel; SE, standard error.