Association between statins and infections among patients with diabetes: a cohort and prescription sequence symmetry analysis

Abstract

PurposeA previous meta‐analysis of randomized trials did not confirm findings from observational studies that suggested that statins reduce the risk of infection. However, animal experiments indicate that statins may be more effective in reducing the risk and/or the severity of infection among patients with diabetes. Hence, we evaluated the effect of statins on antibiotic prescriptions (a proxy for infections) among patients with drug‐treated type 2 diabetes using two confounding‐reducing observational designs.MethodsWe conducted a prescription sequence symmetry analysis and a cohort study using the IADB.nl pharmacy prescription database. For the prescription sequence symmetry analysis, a sequence ratio was calculated. The matched cohort study, comparing the time to first antibiotic prescription between periods that statins are initiated and non‐use periods, was analyzed using stratified Cox regression.ResultsPrescription sequence symmetry analysis of 4684 patients with drug‐treated type 2 diabetes resulted in an adjusted sequence ratio of 0.86 (95% confidence interval [CI]: 0.81 to 0.91). Corresponding figures for the cohort analysis comparing 9852 statin‐initiation with 4928 non‐use periods showed similar results (adjusted hazard ratio: 0.88, 95%CI: 0.83 to 0.95).ConclusionsThese findings suggest that statins are associated with a reduced risk of infections among patients with drug‐treated type 2 diabetes. © 2016 The Authors. Pharmacoepidemiology and Drug Safety Published by John Wiley & Sons Ltd.

A sequence symmetry analysis of the interrelationships between statins, diabetes and skin infections

“…The findings of this study were in contrast to those reported by Pouwels et al ., who reported a reduction in antibiotic use in drug‐treated type 2 diabetic statin users compared to nonusers. Although their research design also utilised SSA, they did not examine the effects of narrow spectrum antibiotics (such as dicloxacillin and flucloxacillin), which target mainly staphylococci, a major bacterial causative agent for SSTIs .…”

“…Marker drugs used were antidiabetic medication (insulins, insulin analogues and oral blood glucose lowering drugs) SSTIs (Figure 5), alluding to statin use as an important contributor to SSTI risk. Viewed collectively, it may be posited that statins are associated with an increased SSTI risk, whether via direct nondiabetogenic mechanisms (Figure 1: direction [i]), or via indirect diabetogenic mechanisms (Figure 1: directions [ii] and [iii]).The findings of this study were in contrast to those reported by Pouwels et al,18 who reported a reduction in antibiotic use in drugtreated type 2 diabetic statin users compared to nonusers. Although their research design also utilised SSA, they did not examine the effects of narrow spectrum antibiotics (such as dicloxacillin and flucloxacillin), which target mainly staphylococci, a major bacterial causative agent for SSTIs 1.…”

“…Although their research design also utilised SSA, they did not examine the effects of narrow spectrum antibiotics (such as dicloxacillin and flucloxacillin), which target mainly staphylococci, a major bacterial causative agent for SSTIs . By studying all β‐lactam penicillins as a group, the effects of broad‐spectrum β‐lactam antibiotics on a variety of both Gram‐positive and Gram‐negative bacteria may mask or confound the results specific to Gram‐positive staphylococci. Hence, it is possible that our results differed despite using the same methodology.…”

“…Although their research design also utilised SSA, they did not examine the effects of narrow spectrum antibiotics (such as dicloxacillin and flucloxacillin), which target mainly staphylococci, a major bacterial causative agent for SSTIs 1. By studying all β-lactam penicillins as a group,18,19 the effects of broad-spectrum β-lactam antibiotics on a variety of both Gram-positive and Gram-negative bacteria may mask or confound the results specific to Gram-positive staphylococci. Hence, it is possible that our results differed despite using the same methodology.Interestingly, although the study by Liappis et al concluded that statins may have a potentially therapeutic role in bacteraemic infections, they noted a statistically significant increase in SSTIs among patients with bacteraemia who were receiving statins, compared to those who were not using statins 20.…”

Is Heterogeneity in the Effects of Statins on Infection Outcomes across Clinical Studies Due to Bias?

“…The results of animal and in vitro studies suggest that statins may be more effective against infections among diabetic patients than among patients without diabetes, by reducing Rac1 activation and/or inhibiting biofilm formation (5-9). Moreover, among patients without diabetes, the potentially smaller benefits may be outweighed by the increased risk of incident diabetes among statin users (5,10).…”