Background: Trial evidence supports statin use after ischemic stroke and recent American, European and British guidelines recommend high-intensity statins for this indication. Limited data are available describing current statin use among these patients in unselected settings. We conducted a cohort study to examine secular trends and factors associated with statin use and dose following ischemic stroke. Methods: A retrospective cohort study of patients with first ischemic stroke between 2000 and 2014 was conducted using the Clinical Practice Research Datalink (CPRD). Proportions of statin users and high-intensity statin users within 2 years after stroke were estimated for each calendar year. We used Cox regression models to explore potential factors associated with statin use and Poisson regression models to calculate risk ratios for the use of a high-intensity statin. Results: A total of 80,442 patients with first stroke were analyzed. The proportion using statins within 2 years after stroke increased from 25% in 2000 to 70% in 2006 and remained at about 75% through 2014. Among post-stroke statin users, high-intensity use accounted for approximately 15% between 2004 and 2011 and then increased to almost 35% in 2014. Older patients (aged ≥75 years), younger patients (<45 years), patients with no prior statin treatment, dementia, underweight, or absence of cardiovascular factors (coronary heart disease, smoking, obesity, diabetes, hypertension, or transient ischemic attack) were less likely to use statins and less likely to receive a high-intensity statin. Conclusion: There has been an increase over time in both statin use and dose, but many patients with ischemic stroke continue to be under-treated. Clinical trials and policy interventions to improve appropriate post-stroke statin use should focus on younger and older patients, patients with no pre-stroke statin treatment, and patients without additional cardiovascular risk factors.

Current evidence is inconclusive on cognitive benefits or harms of statins among stroke patients, who have high risk of dementia. This observational cohort study investigated the association between statin use and post-stroke dementia using data from the Clinical Practice Research Datalink. Patients without prior dementia who had an incident stroke but received no statins in the preceding year were followed for up to 10 years. We used inverse probability weighted marginal structural models to estimate observational analogues of intention-to-treat (ITT, statin initiation vs. no initiation) and per-protocol (PP, sustained statin use vs. no use) effects on the risk of dementia. To explore potential impact of unmeasured confounding, we examined the risks of coronary heart disease (CHD, positive control outcome), fracture and peptic ulcer (negative control outcomes). In 18,577 statin initiators and 14,613 non-initiators (mean follow-up of 4.2 years), the adjusted hazard ratio (aHR) for dementia was 0.70 (95% confidence interval [CI] 0.64–0.75) in ITT analysis and 0.55 (95% CI 0.50–0.62) in PP analysis. The corresponding aHR_ITT and aHR_PP were 0.87 (95% CI 0.79–0.95) and 0.70 (95% CI 0.62–0.80) for CHD, 1.03 (95% CI 0.82–1.29) and 1.09 (95% CI 0.77–1.54) for peptic ulcer, and 0.88 (95% CI 0.80–0.96) and 0.86 (95% CI 0.75–0.98) for fracture. Statin initiation after stroke was associated with lower risk of dementia, with a potentially greater benefit in patients who persisted with statins over time. The observed association of statin use with post-stroke dementia may in part be overestimated due to unmeasured confounding shared with the association between statin use and fracture.

Background: The objective was to evaluate the efficacy of the combination of Glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs), dipeptidyl peptidase‐4 inhibitors (DPP‐4i), and sodium‐glucose cotransporter 2 inhibitor (SGLT‐2i) in the treatment of Type 2 diabetes with poor efficacy of basic insulin and metformin/sulfonylurea by umbrella review.Materials and Methods: Forming the data of publication of each database through 13 September 2022, PubMed, EMBASE, and Cochrane Library were surveyed.Results: A total of seven meta‐analyses were included in the umbrella review. The combination of GLP‐1 RA (WMD −3.41 [−5.61, −1.21], p = 0.002), SGLT‐2i (WMD −5.34 [−9.56, −1.13], p = 0.013), and DPP‐4i (WMD −5.56 [−7.39, −3.73], p ≤ 0.001) can significantly reduce HbA1c levels, respectively. The combination of GLP‐1 RA (WMD −1.55 [−2.92, −0.18], p = 0.027), SGLT‐2i (WMD −2.96 [−6.68, 0.77], p = 0.12), and DPP‐4i (WMD −2.05 [−2.82, −1.28], p ≤ 0.001) can significantly reduce fasting plasma glucose (FPG) levels, respectively. The combination of GLP‐1 RA (WMD −3.24 [−5.14, −1.34], p < 0.001) can significantly reduce body weight of Type 2 diabetes mellitus (T2DM). The dose of basic insulin in diabetes patients after combined use of GLP‐1 RA (WMD −2.74 [−4.26, −1.22], p ≤ 0.001) was significantly reduced. The combination use of GLP‐1 RAs (OR 1.28 [1.05, 1.56], p = 0.017) increases the risk of hypoglycemia.Conclusions: The combination of GLP‐1 RAs, DPP‐4i, and SGLT‐2i can effectively lower HbA1c and FPG in T2DM patients who have poor therapeutic effects on basic insulin combined with metformin/sulfonylureas, respectively. Compared to placebo, GLP‐1 RAs can significantly reduce body weight and basic insulin dosage, while DPP‐4i and SGLT‐2i have a lower risk of hypoglycemia.Trial Registration:CRD42023410345.

Evidence indicates that the polymorphisms in bile salt export pump (BSEP, encoded by ABCB11) may play an important role in the development of anti-tuberculosis drug-induced liver injury (ATDILI) and we aim to investigate the association between genetic variants of ABCB11 and the risk of ATDILI in a Chinese cohort. A total of 89 tuberculosis patients with ATDILI and 356 matched ATDILI -free patients constituted cases and controls. Genetic polymorphisms of ABCB11 were determined by TaqMan single-nucleotide polymorphism (SNP) genotyping assay. Odds ratio (OR) with 95% confidence intervals (CIs) was estimated by conditional logistic regression model. There were no significant differences in genotype frequencies of ABCB11 between cases and controls. In the subgroup analysis, polymorphisms of rs2287616 were found to be associated with cholestatic/mixed pattern of liver injury under dominant and addictive model (OR = 3.84, 95% CI:1.16–12.75, P = 0.028 and OR = 2.51, 95% CI:1.12–5.62, P = 0.025, respectively), however the significance disappeared after Bonferroni correction. This study suggested that genetic variants of ABCB11 gene might contribute to anti-tuberculosis drug-induced cholestatic liver injury in Chinese patients. Studies in larger, varied populations are required to confirm these findings.