Optimal statin use for prevention of sepsis in type 2 diabetes mellitus

Abstract

Purpose

To investigate the dose-dependent protective effects of statins, specific classes of statins, and different intensities of statin use on sepsis risk in patients with type 2 diabetes mellitus (T2DM).

Methods

We included patients with T2DM aged  ≥ 40 years. Statin use was defined as the use of statin on most days for  > 1 months with a mean statin dose of  ≥ 28 cumulative defined daily doses (cDDDs) per year (cDDD-year). An inverse probability of treatment-weighted Cox hazard model was used to investigate the effects of statin use on sepsis and septic shock while considering statin use status as a time-dependent variable.

Results

From 2008 to 2020, a total of 812 420 patients were diagnosed as having T2DM. Among these patients, 118,765 (27.79%) statin nonusers and 50 804 (12.03%) statin users developed sepsis. Septic shock occurred in 42,755 (10.39%) individuals who did not use statins and 16,765 (4.18%) individuals who used statins. Overall, statin users had a lower prevalence of sepsis than did nonusers. The adjusted hazard ratio (aHR) of statin use was 0.37 (95% CI 0.35, 0.38) for sepsis compared with no statin use. Compared with the patients not using statins, those using different classes of statins exhibited a more significant reduction in sepsis, with aHRs (95% CIs) of sepsis being 0.09 (0.05, 0.14), 0.32 (0.31, 0.34), 0.34 (0.32, 0.36), 0.35 (0.32, 0.37), 0.37 (0.34, 0.39), 0.42 (0.38, 0.44), and 0.54 (0.51, 0.56) for pitavastatin, pravastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin use, respectively. In the patients with different cDDD-years of statins, multivariate analysis indicated a significant reduction in sepsis, with aHRs of 0.53 (0.52, 0.57), 0.40 (0.39, 0.43), 0.29 (0.27, 0.30), and 0.17 (0.15, 0.19) for Q1, Q2, Q3, and Q4 cDDD-years ( P for trend < 0.0001). The optimal daily statin dose of 0.84 DDD was associated with the lowest aHR. Similar trends of higher cDDD-year and specific statin types use were associated with a decrease in septic shock when compared to statin non-users.

Conclusion

Our real-world evidence demonstrated that the persistent use of statins reduced sepsis and septic shock risk in patients with T2DM and a higher cDDD-year of statin use was associated with an increased reduction of sepsis and septic shock risk in these patients.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13098-023-01041-w.

Keypoints

Question : Is any real-world evidence of the dose-dependent protective effects of the use of specific classes and intensities of statins on sepsis in type 2 diabetes mellitus (T2DM) available?

Findings: Our study demonstrated that the persistent use of statins (≥28 cumulative defined daily doses per year [cDDD-year]) reduced sepsis risk in T2DM. A higher cDDD-year of statins was associated with greater reduction of sepsis risk in patients with T2DM. Pitavastatin exerted the strongest protective effect on mortality, followed by pravastatin, rosuvastatin, atorvastatin, simvastatin, fluvastatin, and lovastatin. The optimal daily statin dose of 0.84 DDD was associated with the lowest sepsis risk.

Meaning: This is the first study to demonstrate the dose- and intensity-dependent protective effects of different classes of statins on sepsis risk in patients with T2DM.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13098-023-01041-w.