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Introduction: Graves' ophthalmopathy (GO) is an autoimmune inflammatory disorder observed in a substantial proportion of patients with Graves' disease (GD), with debilitating symptoms of disfiguring, periorbital pain, dry eyes, diplopia, and even visual disturbances. Previous studies involving Western populations have noted discrepancies in risk factors for GO. Therefore, this study aimed to determine the risk factors for GO development and the protective effect of statins in newly diagnosed patients with GD in Taiwan. Methods: This retrospective case–control study was based on a tertiary center cohort involving patients with GD diagnosed between 2010 and 2019 at the National Taiwan University Hospital (n = 11,035). Patients who were diagnosed or treated elsewhere, had been followed up for less than 6 months or were with a diagnosis of orbital tumor were excluded. Overall, 3578 patients with GD met the inclusion criteria. Univariate and multivariate logistic regression analyses were used to ascertain the odds ratio (OR) of developing GO, with adjustment for sociodemographic factors, interventions for managing GD and thyroid hormone levels, to determine protective and risk factors for GO. Results: In our multivariate model, the use of statins reduced the risk of GO development (OR 0.2; 95% confidence interval [CI] 0.08–0.50; p < 0.001). Thyroid dysfunction including hyperthyroidism (OR 4.2; 95% CI 2.97–5.88; p < 0.001) and hypothyroidism (OR 4.7; 95% CI 3.02–7.19; p < 0.001) was associated with an increased risk of developing GO. Smoking status and lipid profile were not risk factors in our cohort. Conclusion: In newly diagnosed patients with GD, the use of statins decreased the risk of developing GO by 80%, whereas serum lipid levels were not considered risk factors. Further nationwide population-based studies may help clarify the differences in risk factors between various ethnic groups. Trail Registration: This trial was approved by the Research Ethics Committee of National Taiwan University Hospital (202202066RINC), retrospectively registered from January 1, 2010 to December 31, 2019. [ABSTRACT FROM AUTHOR]

Background and Objectives: Although statins are recommended for secondary prevention of acute ischemic stroke, some population-based studies and clinical evidence suggest that they might be used with an increased risk of intracranial hemorrhage. In this nested case–control study, we used Taiwan's nationwide universal health insurance database to investigate the possible association between statin therapy prescribed to acute ischemic stroke patients and their risk of subsequent intracerebral hemorrhage and all-cause mortality in Taiwan. Materials and Methods: All data were retrospectively obtained from Taiwan's National Health Insurance Research Database. Acute ischemic stroke patients were divided into a cohort receiving statin pharmacotherapy and a control cohort not receiving statin pharmacotherapy. A 1:1 matching for age, gender, and index day, and propensity score matching was conducted, producing 39,366 cases and 39,366 controls. The primary outcomes were long-term subsequent intracerebral hemorrhage and all-cause mortality. The competing risk between subsequent intracerebral hemorrhage and all-cause mortality was estimated using the Fine and Gray regression hazards model. Results: Patients receiving statin pharmacotherapy after an acute ischemic stroke had a significantly lower risk of subsequent intracerebral hemorrhage (p < 0.0001) and lower all-cause mortality rates (p < 0.0001). Low, moderate, and high dosages of statin were associated with significantly decreased risks for subsequent intracerebral hemorrhage (adjusted sHRs 0.82, 0.74, 0.53) and all-cause mortality (adjusted sHRs 0.75, 0.74, 0.74), respectively. Conclusions: Statin pharmacotherapy was found to safely and effectively reduce the risk of subsequent intracerebral hemorrhage and all-cause mortality in acute ischemic stroke patients in Taiwan. [ABSTRACT FROM AUTHOR]

Population aging is a global trend, and the elderly have a higher risk of atherosclerotic cardiovascular disease (ASCVD) and related mortality. Statins have been observed to reduce cardiovascular events in patients with ASCVD. However, compared with secondary prevention, the benefits of statins for primary prevention are undetermined among the elderly. This study aimed to evaluate the effectiveness of statins in an elderly population without a history of cardiovascular disease (CVD). The study was carried out using the National Taiwan University Hospital Integrated Medical Database and the National Health Insurance Research Database in Taiwan. Patients aged 65 years and older without a history of CVD were identified between 1 February 2008 and 31 December 2015. New statin users were 1:4 matched to nonusers based on certain variables. The risks of major adverse cardiovascular events (MACEs) and all-cause mortality were estimated using Cox proportional hazards models. Further, we applied marginal structural models to account for time-varying low-density lipoprotein cholesterol (LDL-C) levels. A total of 2761 new statin users and 9503 nonusers were selected after matching; the mean age was 71.8 years, and 63% were women. At a median follow-up of 4.8 years, statin use was associated with reduced risk of MACEs (hazard ratio [HR]: 0.75; 95% confidence interval [CI], 0.52–0.98) and mortality (HR: 0.72, 95% CI: 0.55–0.93) when accounting for time-varying LDL-C. No significant differences in effect were detected between subgroups. Statin use could be beneficial for the primary prevention of CVD in elderly Asians. • Statin therapy could be beneficial for primary prevention of cardiovascular disease in elderly Asians. • Compared with statin non-users, statin users had significantly lower risks of MACE and all-cause mortality. • The assessment was confirmed by marginal structural models to adjust for confounding effect of time-varying LDL-C levels. [ABSTRACT FROM AUTHOR]

Background: To evaluate the effect of oral statins on the rate of Humphrey visual field progression in patients with open angle glaucoma (OAG). Methods: Patients with primary open angle glaucoma and normal tension glaucoma who had been regularly followed-up in our glaucoma clinic were reviewed for demographic records, statin use history, comorbid medical conditions, and visual field tests. The rate of visual field progression was compared between statin users and nonusers using pointwise liner regression. To further analyze visual field change, we divided Humphrey visual field into twelve subfields and compared the rate of progression accordingly. Results: Sixty-one OAG statin-users and 65 age matched nonusers were enrolled in the study. The mean follow-up period was 9.0 years. The average rate of global visual field progression between the two groups was similar (-0.28 dB/year in statin group and -0.29 dB/year in non-statin group, p = 0.856). However, in subfield analysis, statin users had slower rate of progression in the superior-nasal area (zone 3) than in nonusers (-0.07 dB/year vs. -0.28 dB/year, p = 0.019). Conclusion: The global rate of visual field progression was similar in statin users and nonusers. However, subfield analysis showed that the superior-nasal visual field declined slower in glaucoma patients who received oral statins. [ABSTRACT FROM AUTHOR]

Simple Summary: The incidence of uterine cancer is increasing worldwide in recent decades, especially in the young age population. In parallel, a trend of early onset of diabetes mellitus (DM) and obesity was also observed in the young population. Since DM and obesity are known risk factors of uterine cancer, we proposed to investigate the age-specific risks of uterine cancer in subjects with DM and related metabolic comorbidities. In this nationwide population-based study, we found the risk of uterine cancer in DM subjects was significantly higher in the younger age groups, especially in the age group 30–39 years. Obesity, polycystic ovarian syndrome, hyperlipidemia, statin use, and hormone replacement therapy were also significantly associated with uterine cancer in subjects younger than 50 years of age. Therefore, subjects with DM, especially younger women with respective comorbidities, should be recommended to have appropriate uterine cancer screenings for early detection. Introduction: The global incidence of uterine cancer has increased substantially in recent decades. We evaluated if the trend of increasing prevalence of diabetes mellitus (DM) and obesity are attributed to the development of uterine cancer. Methods: Using data derived from the National Health Insurance database and Taiwan Cancer Registry, multivariate Cox proportional hazards regression models were adapted to analyze the risk factors of uterine cancer with potential confounding variables. Results: There were a total of 5,104,242 women aged 30–70 years enrolled in the study and 147,772 of them were diagnosed with DM during 2005–2007. In a total of 11 years of follow-up, 14,398 subjects were diagnosed with uterine cancer. An elevated risk of uterine cancer was observed in women with DM of all ages (HR 1.66, 95% CI 1.53–1.81, p < 0.0001). The effect of DM was highest at age 30–39 years (RR 3.05, 95% CI 2.35–3.96, p < 0.0001). In the group of <50 years old, DM patients had at least a twofold higher risk of developing uterine cancer (HR 2.39, 95% CI 2.09–2.74, p < 0.0001). Subjects among all ages diagnosed with polycystic ovary syndrome (PCOS) (HR 2.91, 95% CI 2.47–3.42, p < 0.0001), obesity (HR 2.13, 95% CI 1.88–2.41, p < 0.0001), and those undergoing hormone replacement therapy (HRT) (HR 1.60, 95% CI 1.33–1.93, p < 0.0001) were also positively associated with uterine cancer. Positive associations of hyperlipidemia (HR 1.33, 95% CI 1.22–1.46, p < 0.0001) and statin use (HR 1.27, 95% CI 1.12–1.44, p = 0.0002) on uterine cancer were only observed in subjects <50 years. On the contrary, hyperlipidemia was negatively associated with uterine cancer in subjects ≥50 years (HR 0.91, 95% CI: 0.84–0.98, p = 0.0122). Conclusions: DM is in general the most important risk factor for uterine cancer, especially in premenopausal women. Obesity, PCOS, HPL, statin use, and HRT were also associated with uterine cancer in subjects younger than 50 years. Premenopausal women with DM and respective comorbidities should be aware of the development of uterine cancer. [ABSTRACT FROM AUTHOR]

Background/aims: Chronic hepatitis C (CHC) patients who failed antiviral therapy are at increased risk for hepatocellular carcinoma (HCC). This study assessed the potential role of metformin and statins, medications for diabetes mellitus (DM) and hyperlipidemia (HLP), in reducing HCC risk among these patients., Methods: We included CHC patients from the T-COACH study who failed antiviral therapy. We tracked the onset of HCC 1.5 years post-therapy by linking to Taiwan's cancer registry data from 2003 to 2019. We accounted for death and liver transplantation as competing risks and employed Gray's cumulative incidence and Cox subdistribution hazards models to analyze HCC development., Results: Out of 2,779 patients, 480 (17.3%) developed HCC post-therapy. DM patients not using metformin had a 51% increased risk of HCC compared to non-DM patients, while HLP patients on statins had a 50% reduced risk compared to those without HLP. The 5-year HCC incidence was significantly higher for metformin non-users (16.5%) versus non-DM patients (11.3%; adjusted sub-distribution hazard ratio [aSHR]=1.51; P=0.007) and metformin users (3.1%; aSHR=1.59; P=0.022). Statin use in HLP patients correlated with a lower HCC risk (3.8%) compared to non-HLP patients (12.5%; aSHR=0.50; P<0.001). Notably, the increased HCC risk associated with non-use of metformin was primarily seen in non-cirrhotic patients, whereas statins decreased HCC risk in both cirrhotic and non-cirrhotic patients., Conclusion: Metformin and statins may have a chemopreventive effect against HCC in CHC patients who failed antiviral therapy. These results support the need for personalized preventive strategies in managing HCC risk.

Background: For non-dialysis patients with hyperlipidemia, statins may provide clinical benefits in reducing mortality risk; however, the optimal treatment for dialysis patients with hyperlipidemia remains debatable. We evaluated the mortality risks for hyperlipidemic patients with renal disorders associated with statin therapy (ST), using the insurance claims data of Taiwan. Methods: From hyperlipidemic patients diagnosed in 2000–2011, we identified 555,153 patients receiving statin treatment for at least 90 days continuously and 1,141,901 non-statin users, and then randomly selected, from both groups, the propensity score-matched subcohorts of statin users and nonusers in a 1:1 pair by renal function: 415,453 pairs with normal renal function , 43,632 pairs with chronic kidney disease (CKD), and 3,624 pairs with end-stage renal disease (ESRD). We compared the mortalities, by the end of 2016, from all causes, cancer, heart disease, and septicemia between statin users and non-users and between hydrophilic-statin users and lipophilic-statin users. The Cox method estimated ST users to non-user hazard ratios. The time-dependent model was also conducted as sensitivity analysis. Results: The mean ages were 58.7 ± 10.7, 64.2 ± 10.7, and 62.2 ± 10.8 years in normal renal function, CKD, and ESRD groups, respectively. Compared with non-users, statin users had reduced mortality risks from all causes for 32%–38%, from cancer for 37%–46%, from heart disease for 6%–24%, and from septicemia for 17%–21% in all three renal groups. The hydrophilic statin therapy was superior than the lipophilic statin therapy, particularly for reducing deaths from all-causes and cancer. The results under the time-dependent model were similar. Conclusion: Statin therapy is associated with reduced all-causes and non-cardiovascular mortality in ESRD patients. [ABSTRACT FROM AUTHOR]

Background: The long-term effects of statin use on rehospitalization due to ischemic stroke (reHospIS) in hyperlipidemic patients are still unknown. Therefore, we aimed to assess the long-term risks of reHospIS for hyperlipidemic patients who were taking statins and nonstatin lipid-lowering medicines on a regular basis. Methods and Materials: The National Health Insurance Research Database in Taiwan was used to conduct a 6-year cohort study of patients >45 years old (n = 9,098) who were newly diagnosed with hyperlipidemia and hospitalized for the first or second time due to ischemic stroke (IS). The risk of reHospIS was assessed using Cox proportional hazards regression model. Results: Nonstatin lipid-lowering medicines regular users were associated with a higher risk of reHospIS compared to stains users (hazard ratio, HR = 1.29–1.39, p < 0.05). Rosuvastatin was the most preferred lipid-lowering medicine with lower HRs of reHospIS in hyperlipidemic patients whether they developed diabetes or not. Bezafibrate regular users of hyperlipidemic patients developing diabetes (HR = 2.15, p < 0.01) had nearly 50% lower reHospIS risks than those without diabetes (HR = 4.27, p < 0.05). Age, gender, drug dosage, comorbidities of diabetes and heart failure (HF), and characteristics of the first hospitalization due to IS were all adjusted in models. Moreover, increasing trends of HRs of reHospIS were observed from Rosuvastatin, nonstatin lipid-lowering medicines, Lovastatin, and Gemfibrozil to Bezafibrate users. Conclusion: Statins were associated with long-term secondary prevention of reHospIS for hyperlipidemic patients. Rosuvastatin seemed to have the best protective effects. On the other hand, Bezafibrate appears to be beneficial for hyperlipidemic patients developing diabetes. Further research into the combination treatment of statin and nonstatin lipid-lowering medicines in hyperlipidemic patients developing diabetes is warranted. [ABSTRACT FROM AUTHOR]

High-intensity statin (HIS) is recommended for high-risk patients in current guidelines. However, the risk of hemorrhagic stroke (HS) with HIS is a concern for Asians. Pitavastatin carries pharmacological differences compared with other statins. We compared the risk of HS in patients treated with pitavastatin-ezetimibe vs. HIS. We conducted a population-based, propensity score-matched cohort study using data from the Taiwan National Health Insurance Research Database. From January 2013 to December 2018, adults (≥ 18 years) who received pitavastatin 2-4 mg/day plus ezetimibe 10 mg/day (combination group, N = 3,767) and those who received atorvastatin 40 mg/day or rosuvastatin 20 mg/day (HIS group, N = 37,670) were enrolled. The primary endpoint was HS. We also assessed the difference of a composite safety endpoint of hepatitis or myopathy requiring hospitalization and new-onset diabetes mellitus. Multivariable Cox proportional hazards model was used to evaluate the relationship between study endpoints and different treatment. After a mean follow-up of 3.05 ± 1.66 years, less HS occurred in combination group (0.74%) than in HIS group (1.35%) [adjusted hazard ratio (aHR) 0.65, 95% confidence interval (CI) 0.44-0.95]. In subgroup analysis, the lower risk of HS in combination group was consistent among all pre-specified subgroups. There was no significant difference of the composite safety endpoint between the 2 groups (aHR 0.91, 95% CI 0.81-1.02). In conclusion, pitavastatin-ezetimibe combination treatment had less HS compared with high-intensity atorvastatin and rosuvastatin. Pitavastatin-ezetimibe may be a favorable choice for Asians who need strict lipid control but with concern of HS.

Limited information is available regarding the association between statins and pressure ulcers. The purpose of this study is to evaluate the beneficial effects of statins on pressure ulcers in stroke patients. Using the claims data of Taiwan's National Health Insurance, we conducted a retrospective cohort study and identified new-onset stroke patients in 2000–2004. The propensity-score matching procedure was used to select eligible stroke patients with (n = 49,919) and without (n = 49,919) the use of statins. These two groups were followed until the end of 2009 to track the occurrence of pressure ulcers. Multivariate Cox proportional hazard models were conducted to calculate adjusted hazard rations (HRs) and 95% confidence intervals (CIs) of pressure ulcer associated with the use of statins. Stroke patients who used statins had a reduced risk of pressure ulcers during the follow-up period (HR 0.74, 95% CI 0.71–0.78). The association between statin use and a reduced risk of poststroke pressure ulcers was significant in men (HR 0.73, 95% CI 0.68–0.78), women (HR 0.75, 95% CI 0.71–0.80), and people aged more than 50 years. Use of lovastatin, pravastatin, rosuvastatin, atrovastatin, fluvastatin, and simvastatin was associated with reduced poststroke pressure ulcers. There was a dose-dependent decrease in the frequency of pressure ulcers with increasing quantities of statins used, from 1 prescription to ≥3 prescriptions. We raised the possibility that use of statins was associated with reduced risk of pressure ulcers in stroke patients. However, the potential beneficial effect associated with statins requires further validation using randomized clinical trials. Image 1 • Stroke patients using statins had reduced risk of pressure ulcers. • Each subtype of statins was associated with reduced post-stroke pressure ulcers. • A dose-response association existed in statin and reduced post-stroke pressure ulcers. [ABSTRACT FROM AUTHOR]

Background Acute stroke is the third leading cause of death in Taiwan. Although statin therapy is widely recommended for stroke prevention, little is known about the epidemiology of statin therapy after acute ischemic stroke (AIS) in Taiwan. To investigate the effects of statin therapy on recurrent stroke, intracranial hemorrhage (ICH), coronary artery disease (CAD), cost of hospitalization and mortality, we conducted a nationwide population-based epidemiologic study. Methods Cases of AIS were identified from the annual hospitalization discharge diagnoses of the National Health Insurance Research Database with the corresponding International Classification of Diseases, ninth revision codes from January 2001 to December 2010. We divided the AIS patients into three groups: non-statin, pre-stroke statin and post-stroke statin. Results A total of 422 671 patients with AIS (including 365 419 cases in the non-statin group, 22 716 cases in the pre-stroke statin group and 34 536 cases in the post-stroke statin group) were identified. When compared to the non-statin group, both statin groups had a lower recurrent stroke risk [pre-stroke statin: odds ratio (OR) = 0.84; 95% confidence interval (CI) = 0.82–0.87; P  <   0.0001; post-stroke statin: OR = 0.89; 95% CI = 0.86–0.91; P  <   0.0001], lower ICH risk (pre-statin: OR = 0.75; 95% CI = 0.69–0.82; P  <   0.0001; post-stroke statin: OR = 0.75; 95% CI = 0.71–0.81; P  <   0.0001), and a lower mortality rate (pre-stroke statin: OR = 0.56; 95% CI = 0.53–0.59; P  <   0.0001; post-stroke statin: OR = 0.51; 95% CI = 0.48–0.53; P  <   0.0001). In terms of CAD, only the post-statin group had a lower risk (OR = 0.81; 95% CI = 0.79–0.84; P  <   0.0001) than the non-statin group. The post-statin group had the lowest 1-year medical costs after index discharge among the three groups. Conclusions Statin therapy reduced the risks of recurrent stroke, CAD, ICH and the first year mortality in patients after AIS. Treatment with statin therapy after AIS is a cost-effective strategy in Taiwan. [ABSTRACT FROM AUTHOR]

Background: Secondary prevention therapy for patients with coronary artery disease using an antiplatelet agent, β-blocker, renin-angiotensin system blocker (RASB), or statin plays an important role in the reduction of coronary events after coronary artery bypass grafting (CABG) surgery or percutaneous coronary intervention (PCI). We analyzed the status and effects of secondary prevention after coronary revascularization in Taiwan. Methods: This national population-based cohort study was conducted by analyzing the Longitudinal Health Insurance Database 2000 from the National Health Insurance Research Database of Taiwan. Patients who underwent CABG or PCI from 2004 to 2009 were included in the analysis. The baseline characteristics of the patients and ACC/AHA class I medication use at 12 months were analyzed. The primary endpoints were a composite of major adverse cardiac and cerebrovascular events. Results: A total of 5544 patients comprising 895 CABG and 4649 PCI patients were evaluated. CABG patients had more comorbidities and a higher rate of major adverse event during the follow-up period. However, use of antiplatelet agents and RASB at 12 months was significantly lower in CABG patients than in PCI patients (44.2% vs. 50.9% and 38.6% vs. 48.9%, both p < 0.01). Age, diabetes, and chronic kidney disease were independent risk factors while statin use was a protective factor for the primary endpoints in both PCI and CABG groups. Conclusion: There is still much room to improve class I medication use in secondary prevention for patients after revascularization in Taiwan. Statin could be an effective treatment to improve the outcomes. [ABSTRACT FROM AUTHOR]

Background/objective:Potential association between prior statin use and chronic osteomyelitis is examined. Methods:A nationwide case–control study was conducted based on data taken from the Taiwan National Health Insurance program. The case group includes 2338 subjects aged 20–84 years newly diagnosed for chronic osteomyelitis from 2000 to 2013; the control group included 2338 randomly selected subjects without chronic osteomyelitis matched for sex, age, and index year. Statin use was respectively defined as “current”, “recent” or “past” if the most recent statin prescription was filled <3 months, 3–6 months or ≥6 months prior to the chronic osteomyelitis diagnosis. Relative risk of chronic osteomyelitis associated with statin use was measured by the odds ratio (OR) with 95% confidence interval (CI) using the conditional logistic regression model. Results:After controlling for potential confounders, the adjusted ORs of chronic osteomyelitis were 0.57 for subjects with current statin use (95% CI 0.45, 0.72), 0.80 for subjects with recent statin use (95% CI 0.48, 1.33), and 1.00 for subjects with past statin use (95% CI 0.83, 1.20), compared patients with no prior statin use. In further analysis, the adjusted ORs of chronic osteomyelitis were 0.70 for subjects with cumulative statin use <12 months (95% CI 0.47, 1.07), and 0.56 for subjects with cumulative statins use ≥12 months (95% CI 0.41, 0.77), compared with those with no prior statin use. Conclusions:Current statin use is associated with reduced concurrent diagnosis of chronic osteomyelitis, particularly for a cumulative statin use ≥12 months. [ABSTRACT FROM PUBLISHER]

The relationship between cholesterol level and hemorrhagic stroke is inconclusive. We hypothesized that low cholesterol levels may have association with intracerebral hemorrhage (ICH) severity at admission and 3-month outcomes. This study used data obtained from a multi-center stroke registry program in Taiwan. We categorized acute spontaneous ICH patients, based on their baseline levels of total cholesterol (TC) measured at admission, into 3 groups with <160, 160–200 and >200 mg/dL of TC. We evaluated risk of having initial stroke severity, with National Institutes of Health Stroke Scale (NIHSS) >15 and unfavorable outcomes (modified Rankin Scale [mRS] score >2, 3-month mortality) after ICH by the TC group. A total of 2444 ICH patients (mean age 62.5±14.2 years; 64.2% men) were included in this study and 854 (34.9%) of them had baseline TC <160 mg/dL. Patients with TC <160 mg/dL presented more often severe neurological deficit (NIHSS >15), with an adjusted odds ratio [aOR] of 1.80; 95% confidence interval [CI], 1.41–2.30), and 3-month mRS >2 (aOR, 1.41; 95% CI, 1.11–1.78) using patients with TC >200 mg/dL as reference. Those with TC >160 mg/dL and body mass index (BMI) <22 kg/m2 had higher risk of 3-month mortality (aOR 3.94, 95% CI 1.76–8.80). Prior use of lipid-lowering drugs (2.8% of the ICH population) was not associated with initial severity and 3-month outcomes. A total cholesterol level lower than 160 mg/dL was common in patients with acute ICH and was associated with greater neurological severity on presentation and poor 3-month outcomes, especially with lower BMI. [ABSTRACT FROM AUTHOR]

To investigate the relationship between chronic liver disease and tendon disorder, a retrospective cohort study was conducted using the Kaohsiung Veterans General Hospital database. Patients >18 years with newly diagnosed liver disease and with at least a two-year follow-up in the hospital were included. An equal number of 20,479 cases were enrolled in both the liver-disease and non-liver-disease groups using a propensity score matching method. Disease was defined using ICD-9 or ICD-10 codes. The primary outcome was the development of tendon disorder. Demographic characteristics, comorbidities, use of tendon-toxic drugs, and status of HBV/HCV infection were included for analysis. The results showed 348 (1.7%) and 219 (1.1%) individuals developed tendon disorder in the chronic liver disease group and non-liver-disease group. Concomitant use of glucocorticoids and statins may have further raised the risk of tendon disorder in the liver disease group. The co-existence of HBV/HCV infection did not increase the risk of tendon disorder in the patients with liver disease. Considering these findings, physicians should be more aware of tendon issues in advance, and a prophylactic strategy should be adopted in patients with chronic liver disease.

Background: Statins have been reported to prevent adverse cardiovascular events in patients with myocardial infarction (MI). However, the association of statin use and the risk of pneumonia requiring hospitalization in MI patients remains unclear.Methods: A nested case-control study was conducted by using data from the National Health Insurance Research Database of Taiwan. Among 24,975 patients with MI, 2686 case patients with pneumonia requiring hospitalization were age- and sex-matched with 10,726 control patients using the incidence density sampling approach. Duration and dosage of statin use were obtained from pharmaceutical claims. Conditional logistic regression analyses were used to estimate the risk of hospitalization for pneumonia associated with statin use adjusted for patient's demographics, medical conditions and prescribed medications.Results: Statin use was associated with a 15% reduced risk of pneumonia requiring hospitalization among MI patients (adjusted odds ratio [aOR] = 0.85, 95% confidence interval [CI] = 0.77-0.95, P = 0.004). The association was more significant for MI patients unexposed to statin pretreatment (aOR = 0.76, 95% CI = 0.64-0.90, P = 0.001). Statins also exhibited favorable benefits in a time- and dose-dependent manner. The results were consistent in various subgroup analysis of the patients who were female, age ≥ 65 years, a low CHADS2 (i.e. congestive heart failure, hypertension, diabetes mellitus, previous stroke and age > 75 years old) score, and fewer comorbidities. Atorvastatin, fluvastatin and simvastatin were the most common prescribed statins and had similar effects.Conclusions: Statins might be considered as an adjunctive therapy to reduce the risk of hospitalization for pneumonia for MI patients under thorough evaluation of individual comorbidities, previous statin use and optimal dosage. [ABSTRACT FROM AUTHOR]

Background and purpose Statin therapy is beneficial for primary and secondary prevention of ischaemic stroke, but its influence in patients with intracerebral hemorrhage ( ICH) is unclear. An assessment was made of the effect of early statin therapy on patients with acute ICH. Methods Taiwan's National Health Insurance Research Database was screened for patients without prior statin therapy admitted from January to December 2008 for newly diagnosed ICH. Patients taking statins during hospitalization or within 3 months post-discharge were the early statin group ( n = 749); patients who were not were the control group ( n = 7583). The study end-points were recurrent ICH and all-cause mortality during follow-up. Results All eligible patients were followed up until 31 December 2010. During the follow-up, 69 (9.2%) patients in the early statin group and 677 (8.9%) control group patients had recurrent ICH. Cox proportional hazards analyses showed that early statin use did not increase the risk of recurrent ICH (adjusted hazard ratio 1.044; 95% confidence interval 0.812-1.341). During the same period, 90 (12.0%) of the early statin group and 1519 (20.0%) control group patients died. All-cause mortality was lower in the early statin group (adjusted hazard ratio 0.742; 95% confidence interval 0.598-0.919) than in the control group. Matched propensity score analyses were consistent with findings in Cox proportional hazards analyses. Conclusions Early statin group patients with acute ICH did not have a higher recurrent risk of ICH and might have lower all-cause mortality during follow-up. It is concluded that statin therapy might be beneficial for patients with ICH. [ABSTRACT FROM AUTHOR]

Objective Depression is a highly prevalent disorder that is associated with disability. The aim of this study was to determine the relationship between depression and hyperlipidemia and whether the onset of depression is associated with administering statins to patients with hyperlipidemia. Material and Methods The data analyzed in this study were retrieved from the National Health Insurance Research Database in Taiwan. We identified newly diagnosed hyperlipidemia in 26,852 patients without a history of depression as the exposure group in the period of 2000-2002, and a comparison group comprised 107,408 patients. The differences between the exposure group and the comparison group were examined using a chi-square test to calculate categorical variables. The hazard ratio and the 95% confidence interval for depression were used in the logistic regression. Results The hyperlipidemia patients demonstrated a high risk for depression and comorbidities, such as hypertension, diabetes and sleep disorder, which indicated synergistic effects related to a high risk of depression in hyperlipidemia patients. Hyperlipidemia patients who had received statins exhibited a lower risk of depression than did those who had not received statins. Conclusion Our results suggested that hyperlipidemia increases the risk of depression and that using statins is associated with a decreased risk of depression in patients with hyperlipidemia. [ABSTRACT FROM AUTHOR]

It was suggested that statin may improve the outcomes of pneumonia patients. However, there are sparse data regarding this topic in ethnic Chinese populations. In the present study, we investigated associations between previous statin use and pneumonia outcomes in Taiwan with a large-scale matched cohort study. A total of 11 576 patients with pneumonia were selected, comprising 2894 patients with previous statin use and 8682 matched patients. We used a separate conditional logistic regression to explore relationships between statin use and each clinical outcome, including 'intensive care unit admission,' 'use of mechanical ventilation,' 'acute respiratory failure' and 'in-hospital death'. We found that patients who were statin users were 0.81 (95% CI 0.74-0.89), 0.80 (95% CI 0.71-0.89), 0.84 (95% CI 0.75-0.94) and 0.69 times (95% CI 0.57-0.85) less likely to be admitted to the intensive care unit, to have acute respiratory failure, to need mechanical ventilation, and to die in the hospital, respectively, than patients who were not statin users. In addition, it consistently revealed that compared with patients who were not statin users, regular statin users had lower ORs of intensive care unit admission, acute respiratory failure, the use of mechanical ventilation and in-hospital death. However, there were no significant differences in the above adverse outcomes between irregular users of statin and non-statin users. We concluded that patients with regular previous statin use were significantly associated with favourable outcomes during admission for pneumonia in Taiwan. [ABSTRACT FROM AUTHOR]

Abstract: Background: To contain cost, Taiwan's previous National Health Insurance Reimbursement Policy requested that physicians discontinue their patients' statin therapy once the serum cholesterol had reached appropriate levels. This allowed us to evaluate the association between statin continuation and the occurrence of atrial fibrillation/flutter and whether it was modified by chronic kidney disease (CKD) status. Methods: Patients who initiated statin therapy between January 1, 2001 and December 31, 2009 were identified from a random sample of one million subjects in the Taiwan National Health Insurance Research Database. The outcome was atrial fibrillation/flutter. A proportional hazard regression model with time-varying statin use was applied to estimate the hazard ratios (HR) and 95% confidence intervals (CIs) for atrial fibrillation/flutter according to current statin use versus treatment discontinuation, adjusted for baseline disease risk scores and time-varying covariates. Results: A total of 6767 CKD and 63,678 non-CKD patients initiating statin therapy were included and followed for an average of 4.0 years. A total of 1118 participants experienced new-onset atrial fibrillation/flutter. The incidence of atrial fibrillation/flutter was approximately 2 fold higher in the CKD patients. Continuation of statin therapy was associated with a 22% (adjusted hazard ratio 0.78; 95% CI: 0.65–0.93) and 57% (adjusted HR 0.43; 95% CI: 0.27–0.68) decrease in atrial fibrillation/flutter hazard as compared with discontinuation in non-CKD and CKD patients, respectively. Conclusions: Continuation of statin therapy was associated with a decreased risk of atrial fibrillation/flutter among CKD and non-CKD patients. However, further randomized studies are still needed to assess the association. [Copyright &y& Elsevier]

Osteoporosis is a common disease in the elderly population. The progress of this disease results in the reduction of bone mass and can increase the incidence of fractures. Drugs presently used clinically can block the aggravation of this disease. However, these drugs cannot increase the bone mass and may result in certain side effects. Statins, also known as HMG-CoA (3-hydroxy-3-methylglutaryl-CoA) reductase inhibitors, have been widely prescribed for CVD (cardiovascular disease) for decades. Nonetheless, several studies have demonstrated that statins exert bone anabolic effect and may be helpful for the treatment of osteoporosis. Several experiments have analysed the mechanisms of bone anabolism regulated by statins. In the present paper, we review the mechanisms of promoting osteogenesis, suppressing osteoblast apoptosis and inhibiting osteoclastogenesis. [ABSTRACT FROM AUTHOR]

Abstract: Background: The proper use of statins and aspirin decrease the risk of coronary heart disease (CHD) among patients with diabetes (DM) and hyperlipidemia. The purpose of this study was to analyze the time trends and determinants of prescribing statins and aspirin among patients with DM and hyperlipidemia in medical practice in Taiwan. Methods: A cohort of 21,667 patients with DM and hyperlipidemia during the period from 1998 to 2006 was identified by using data of ambulatory care claims from Taiwan''s National Health Insurance Database. The dataset was categorized into two equal calendar periods: Period 1 (September 1998–June 2002) and Period 2 (July 2002–April 2006). Multivariate logistic regression analyses were used to determine the independent determinants associated with receipt of lipid-lowering agents and aspirin among these patients. Results: There were significant increases in the prescribing of statins (OR 1.78; 95% CI 1.66−1.91) and aspirin (OR 1.47, 95% CI 1.50−1.59) in Period 2 as compared with Period 1. Nevertheless, 30% of patients with coexisting CHD neither received statins nor aspirin. Only 15% to 25% of DM patients with hyperlipidemia and CHD received the combined treatment with aspirin and statin. In multivariate logistic regression, we found that women received aspirin less frequently than men. Old patients (>45 years) with concomitant CHD were more likely to receive statins and aspirin. Conclusion: Despite the increasing trend in the use of statins and aspirin in DM patients with hyperlipidemia in Taiwan, the improvements were at best modest, particularly for secondary prevention. Our data indicate the need for continued efforts to improve the utilization of these drugs in daily practice. [Copyright &y& Elsevier]

Abstract: Background: Statins have been linked to new-onset diabetes (NOD); however, the effect of statins on the development of NOD in patients with hypertension and dyslipidemia has not been well studied. Objective: The goal of this study was to investigate the association between statins and NOD. Methods: This was a retrospective cohort study performed by using data from claim forms provided to the central regional branch of the Bureau of National Health Insurance in Taiwan from July 2006 to December 2009. Prescriptions for statins before the index date were retrieved from a prescription database. We estimated the hazards ratios (HRs) of NOD associated with statin use. Nondiabetic subjects served as the reference group. Results: A total of 1360 (8.5%) NOD cases were identified among 16,027 patients with hypertension and dyslipidemia during the study period. The risk of NOD after adjusting for sex and age was higher among users of pravastatin (HR, 1.34 [95% CI, 1.15–1.55]) and atorvastatin (HR, 1.29 [95% CI, 1.16–1.44]) than among nonusers. Patients who took fluvastatin (HR, 0.45 [95% CI, 0.34–0.60]), lovastatin (HR, 0.71 [95% CI, 0.61–0.84]), and rosuvastatin (HR, 0.54 [95% CI, 0.39–0.77]) were at lower risk of developing NOD than nonusers. Simvastatin was not associated with risk of NOD. Furthermore, the risk of NOD after adjusting for concomitant medication usage and mean dose of statins was neutral among users of atorvastatin. Pravastatin, fluvastatin, lovastatin, simvastatin, and rosuvastatin produced similar results as adjusting for sex and age. Conclusions: These outpatients with hypertension and dyslipidemia who took fluvastatin, lovastatin, and rosuvastatin were at lower risk of NOD, whereas patients who took pravastatin were at greater risk. Simvastatin and atorvastatin seemed to have a neutral effect. Our study also demonstrated that atorvastatin has a dose-response effect on NOD risk. Because this was a descriptive study, temporality and subsequent causality of all statins and NOD could not be shown. Further study and independent confirmation of the causality between statin use and NOD in larger clinical trials are warranted. [Copyright &y& Elsevier]

Abstract: The aim of this study was to investigate whether the use of statins was associated with lung cancer risk. We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National health Insurance Research Database. Cases consisted of all female patients who were aged 50 years and older and had a first-time diagnosis of lung cancer for the period between 2005 and 2008. We identified four control patients per case patient. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated by using multiple logistic regression. We examined 297 female lung cancer cases and 1188 controls. The unadjusted odds ratios (ORs) for any statin prescription were 0.78 (95% confidence interval=0.57–1.07) and the adjusted OR was 0.82 (95% CI=0.58–1.15). Compared with no use of statins, the adjusted ORs were 0.83 (95% CI=0.54–1.28) for the group having been prescribed statins with cumulative defined daily dose (DDDs) below 92.41 and 0.79 (95% CI=0.50–1.25) for the group with cumulative statin use of 92.41 DDDs or more. The present data do not provide support for a beneficial association between statin use and female lung cancer risk. [Copyright &y& Elsevier]

Abstract: Background: Conflicting results using the combination of ezetimibe and statins to reduce the risk of cardiovascular events in patients with acute coronary syndrome (ACS) have been reported. Objective: The aim of this work was to assess the effectiveness of ezetimibe coadministered with statins in reducing cardiovascular events in patients with ACS. Methods: A retrospective cohort study of patients discharged after hospitalization with ACS was conducted from January 1, 2006, to December 31, 2007, and included those who were prescribed statins alone (n = 37,753) and those who received ezetimibe plus statins (n = 1001) within 365 days after the hospitalization, based on patient data obtained from the National Health Insurance Research Database (NHIRD) in Taiwan. The propensity score method was used to identify a 1:1 matched cohort (n = 2002). Risk of rehospitalization for ACS was analyzed by a multivariable Cox proportional hazards regression model. Results: The crude event rate of rehospitalization due to ACS in the original cohort was 13.4 per 100 person-years (268 events) in the combination group and 22.6 per 100 person-years (12,724 events) in the statins-alone group (adjusted hazard ratio [HR] 0.69; 95% CI, 0.62–0.78). The crude event rates of rehospitalization due to ACS in the matched cohort were 13.4 and 20.0 per 100 person-years in the combination group and statins-alone group, respectively (HR 0.62; 95% CI, 0.53–0.73). Compared with statins alone, the adjusted HRs for rehospitalization for percutaneous transluminal coronary angioplasty without stent, with stent, and revascularization for the combination group in the matched cohort were 0.61 (0.50–0.75), 0.62 (0.48–0.81), and 0.62 (0.51–0.76), respectively. Conclusions: Based on the data of Taiwan''s NHIRD, our findings suggest that patients with ACS on ezetimibe combined with statins had a significantly lower risk of rehospitalization due to ACS, percutaneous transluminal coronary angioplasty, and revascularization than those on statins alone. The generalization of the results is limited because of using claims data of a specific population as the data source. [Copyright &y& Elsevier]

Context: Fenofibrate provides limited cardiovascular (CV) benefits in the general population; however, little is known about its benefit among advanced chronic kidney disease (CKD) patients., Objective: This study compared outcomes among advanced CKD patients treated with fenofibrate, statins, a combination of both, and none of these., Methods: This national cohort study was based on Taiwan's National Health Insurance Research Database. Patients younger than 20 years with advanced CKD were identified and further divided into 4 groups according to treatment. The inverse probability of treatment weighting was used to balance baseline characteristics. Patients received fenofibrate, statins, a combination of fenofibrate and statins, or none of these in the 3 months preceding the advanced CKD date. Main outcome measures included all-cause mortality, CV death, and incidence of permanent dialysis., Results: The fenofibrate and statin groups exhibited a lower risk of CV death (fenofibrate vs nonuser: hazard ratio [HR]: 0.84; 95% CI, 0.75-0.94; statins vs nonuser: HR: 0.94; 95% CI, 0.90-0.97) compared with the nonuser group. The fenofibrate group further exhibited the lowest incidence of permanent dialysis (fenofibrate vs nonuser: subdistribution HR [SHR]: 0.78; 95% CI, 0.77-0.80; statins vs fenofibrate: SHR: 1.27; 95% CI, 1.26-1.29; combination vs fenofibrate: SHR: 1.15; 95% CI, 1.13-1.17). Furthermore, the combined administration of fenofibrate and high-intensity statins exhibited a lower risk of major adverse cardiac and cerebrovascular events., Conclusion: For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high-intensity statins may have additional benefits., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Aim: Chronic kidney disease (CKD) is associated with unfavorable outcomes in patients with ischemic stroke. One major metabolic derangement of CKD is dyslipidemia, which can be managed by statins. This study aimed to investigate whether the association of statins with post-stroke outcomes would be affected by renal function., Methods: We evaluated the association of statin therapy at discharge with 3-month outcomes according to the estimated glomerular filtration rate (eGFR) of 50,092 patients with acute ischemic stroke from the Taiwan Stroke Registry from August 2006 to May 2016. The outcomes were mortality, functional outcome as modified Rankin Scale (mRS), and recurrent ischemic stroke at 3 months after index stroke., Results: Statin therapy at discharge was associated with lower risks of mortality (adjusted hazard ratio [aHR], 0.41; 95% confidence interval [CI], 0.34 to 0.50) and unfavorable functional outcomes (mRS 3-5; aHR, 0.80; 95% CI, 0.76 to 0.84) in ischemic stroke patients. After stratification by eGFR, the lower risk of mortality associated with statins was limited to patients with an eGFR above 15 mL/min/1.73 m 2 . Using statins at discharge was correlated with a lower risk of unfavorable functional outcomes in patients with an eGFR of 60-89 mL/min/1.73 m 2 . Statin therapy in patients with an eGFR of 60-89 mL/min/1.73 m 2 may be associated with a higher risk of recurrent ischemic stroke compared with nonusers (aHR, 1.29; 95% CI, 1.07 to 1.57)., Conclusions: In patients with acute ischemic stroke, the associations of statins with mortality and functional outcomes was dependent on eGFR.

Aim: We aimed to evaluate the long-term risk of dementia in patients with periodontitis and its associated factors., Materials and Methods: Using Taiwan's National Health Insurance Database, we identified 56,018 patients aged ≥50 years with newly diagnosed periodontitis in 2000-2008. A cohort of 56,018 adults without periodontitis was selected for comparison, with matching by age and sex. Both cohorts were followed from 2000 to the end of 2013, and incident dementia was identified during the follow-up period. Adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) of dementia associated with periodontitis were calculated in the multivariate regressions., Results: Periodontitis was associated with dementia risk (HR: 1.79, 95% CI: 1.67-1.93), and the association between periodontitis and dementia risk was significant in men, women, and people aged more than 60 years. Among patients with periodontitis, the use of statins (HR: 0.78, 95% CI: 0.71-0.87), metformin (HR: 0.53, 95% CI: 0.44-0.62), and influenza vaccination (HR: 0.67, 95% CI: 0.61-0.74) were associated with a reduced risk of dementia, while diabetes, mental disorders, and stroke were major significant risk factors., Conclusions: Periodontitis was a risk factor for dementia, while the use of statins and metformin may reduce the risk of dementia., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Statins inhibit cholesterol biogenesis and modulate atheroma inflammation to reduce cardiovascular risks. Promoted by immune and non-immune cells, serum C-reactive protein (CRP) might be a biomarker suboptimal to assess inflammation status. Although it has been reported that statins modulated inflammation via microRNAs (miRNAs), evidence remains lacking on comprehensive profiling of statin-induced miRNAome alterations in immune cells. We recruited 19 hypercholesterolemic patients receiving 2 mg/day pitavastatin and 15 ones receiving 10 mg/day atorvastatin treatment for 12 weeks, and performed microarray-based profiling of 1733 human mature miRNAs in peripheral blood mononuclear cells (PBMCs) before and after statin treatment. Differentially expressed miRNAs were determined if their fold changes were >1.50 or <0.67, after validated using quantitative polymerase chain reaction (qPCR). The miRSystem and miTALOS platforms were utilized for pathway analysis. Of the 34 patients aged 63.7 ± 6.2 years, 27 were male and 19 were with coronary artery disease. We discovered that statins induced differential expressions of miR-483-5p, miR-4667-5p, miR-1244, and miR-3609, with qPCR-validated fold changes of 1.74 (95% confidence interval, 1.33-2.15), 1.61 (1.25-1.98), 1.61 (1.01-2.21), and 1.68 (1.19-2.17), respectively. The fold changes of the four miRNAs were not correlated with changes of low-density-lipoprotein cholesterol or CRP, after sex, age, and statin type were adjusted. We also revealed that RhoA and transforming growth factor-β signaling pathways might be regulated by the four miRNAs. Given our findings, miRNAs might be involved in statin-induced inflammation modulation in PBMCs, providing likelihood to assess and reduce inflammation in patients with atherosclerotic cardiovascular diseases., (© 2020 The Author(s).)

It remains uncertain whether statin use is associated with the risks of tuberculosis (TB) and herpes zoster in patients with type 2 diabetes. This study aims to assess the effects of statins vs nonstatin lipid-lowering agents on the risk of these infectious diseases in patients with diabetes., Methods: Participants in the Taiwan National Health Insurance Research Database diagnosed with type 2 diabetes in 2001-2013 were classified as statin users, nonstatin users and lipid-lowering drug-free groups. Participants were observed for incident TB and herpes zoster from diabetes diagnosis until treatment crossover or December 2013. Statin user and nonstatin user were the time-dependent variables in Cox regression analysis., Results: Over 240 782 person-years of observation, statin users (n = 17 696) were associated with a lower TB risk than nonstatin users (n = 5327) and the drug-free group (n = 22 316) (adjusted hazard ratio [aHR]: 0.66; 95% confidence interval [CI]: 0.44-0.99 and aHR: 0.57; 95% CI: 0.44-0.73). Compared with nonstatin users, statin users showed a dose-dependent association with TB risk (low-potency statin users, aHR: 0.692; 95% CI: 0.455-1.053; high-potency users, aHR: 0.491; 95% CI: 0.241-0.999). Statin users presented with a higher risk of herpes zoster than nonstatin users and the drug-free group (aHR: 1.23; 95% CI: 1.01-1.50 and aHR: 1.20; 95% CI: 1.09-1.33). The risks of TB and herpes zoster were not statistically different between nonstatin users and the drug-free group., Conclusion: Compared with nonstatin drugs, statin use was specifically associated with a decreased risk of TB but a moderately increased risk of herpes zoster in this cohort study., (© 2019 The British Pharmacological Society.)

Background : Previous research found that statins, in addition to its efficiency in treating hyperlipidemia, may also incur adverse drug reactions, which mainly include myopathies and abnormalities in liver function. Aim: This study aims to assess the risk for newly onset sarcopenia among patients with chronic kidney disease using statins. Material and Method: In a nationwide retrospective population-based cohort study, 75,637 clinically confirmed cases of chronic kidney disease between 1997 and 2011were selected from the National Health Insurance Research Database of Taiwan. The selection of the chronic kidney disease cohort included a discharge diagnosis with chronic kidney disease or more than 3 outpatient visits with the diagnosis of chronic kidney disease found within 1 year. After consideration of patient exclusions, we finally got a total number of 67,001 cases of chronic kidney disease in the study. The Cox proportional hazards model was used to perform preliminary analysis on the effect of statins usage on the occurrence of newly diagnosed sarcopenia; the Cox proportional hazards model with time-dependent covariates was conducted to take into consideration the individual temporal differences in medication usage, and calculated the hazard ratio (HR) and 95% confidence interval after controlling for gender, age, income, and urbanization. Results: Our main findings indicated that patients with chronic kidney disease who use statins seem to effectively prevent patients from occurrences of sarcopenia, high dosage of statins seem to show more significant protective effects, and the results are similar over long-term follow-up. In addition, the risk for newly diagnosed sarcopenia among patients with lipophilic statins treatment was lower than that among patients with hydrophilic statins treatment. Conclusion: It seems that patients with chronic kidney disease could receive statin treatment to reduce the occurrence of newly diagnosed sarcopenia. Additionally, a higher dosage of statins could reduce the incidence of newly diagnosed sarcopenia in patients with chronic kidney disease., Competing Interests: The authors declare no conflicts of interest.

Background: Atrial fibrillation (AF)-related stroke causes severe disability and poor prognosis. Adjunctive statin therapy has been recommended for atherosclerotic-related stroke but not AF-related stroke. This study investigated the effects of statin in AF patients who experienced acute ischemic stroke., Methods: Data from patients with AF experiencing first-ever ischemic stroke between 2001 and 2010 were collected from the Taiwan National Health Insurance Research Database and categorized into non-statin and statin groups. The statin group was further divided into pre-stroke statin (those who began statin therapy before stroke) and post-stroke statin (those who began statin therapy after stroke) groups. The risks for recurrent ischemic stroke, coronary artery disease (CAD), intracranial hemorrhage (ICH), and 1-year mortality were compared among the groups., Results: A total of 43,242 patients were in the non-statin, 2858 in the pre-stroke statin and 4640 in post-stroke statin groups. Comparing the risk for recurrent stroke and CAD among the three groups, the pre-stroke statin and post-stroke statin groups did not exhibit a significant difference compared with the non-statin group. In terms of ICH risk, the statin group had a lower risk for ICH (odds ratio [OR] 0.79, 95% confidence interval [CI] 0.68-0.90; p = 0.0007) compared with the non-statin group. The overall 1-year mortality in both statin subgroups was lower than that in the non-statin group (pre-stroke statin, OR 0.55 [95% CI 0.49-0.61]; p < 0.0001 versus post-stroke statin, OR 0.53 [95% CI 0.48-0.58]; p < 0.0001)., Conclusions: Statin therapy reduced the risk of ICH and 1-year mortality in AF patients who experienced acute ischemic stroke., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Background: Despite the recommendations of statins treatment for secondary prevention of atherosclerotic cardiovascular disease (ASCVD), treatment adherence and persistence are still a concern. This study examined the real world practice of long-term adherence and persistence to statins treatment initiated after hospital discharge for ASCVD, and their associated factors in a nationwide cohort.Methods: Post discharge statin prescriptions between 2006 and 2012 were extracted from the Taiwan National Health Insurance claims database. Good adherence, defined as proportion of days covered (PDC) ≥0.8 and mean medication possession ratio (MPR), was measured every 180-day period. Non-persistence was defined on the date patients failed to refill statin for 90 days after the end of the last prescription. Their associations with influential factors were analyzed using a generalized estimating equation and Cox's proportional hazard model.Results: There was a total of 185,252 post-discharge statin initiations (from 169,624 patients) and followed for 467,398 patient-years in the study cohort. Percentage of good adherence (mean MPR) was 71% (0.87) at 6-months; declined to 54% (0.68), 47% (0.59), and 42% (0.50) at end of year 1, 2, and 7, respectively. Persistence in statin treatment was 86, 67, 50, and 25% at 6-month, 1-, 2-, and 7-year, respectively. Comparing the statin-cohort initiated from year 2006 to 2012, 1-year persistence increased from 58 to 73%, and 1-year good adherence improved from 45 to 61%. Factors associated with sub-optimal adherence and non-persistence included: prescription by primary care clinics or non-cardiology specialties; patients' age > 75 years; no history of previous statin use; ASCVD events with ischemic stroke diagnosis; comorbidities of renal disease, liver disease, depression, and chronic obstructive pulmonary disease.Conclusions: Despite the improving trends, long-term adherence and persistence of statin treatment were suboptimal in Taiwan. Strategies to maintain statin treatment adherence and persistence need to be implemented to further enhance the positive trend. [ABSTRACT FROM AUTHOR]

Background: Low HDL-C is a common lipid phenotype in Asia. Although low HDL-C is a risk factor of atherosclerotic cardiovascular disease (ASCVD) in general population, it is controversial whether the on-treatment HDL-C level is still a predicting factor of cardiovascular (CV) events in ASCVD patients (pts) under statin treatment. Methods and Results: A total of 3,731 pts (age 65.6 yrs, 75% men) receiving statins were selected from the Taiwanese Secondary Prevention for patients with AtheRosCLErotic disease (T-SPARCLE) Registry, a multicenter, observational study of adult pts with stable coronary artery disease (CAD), cerebrovascular disease, or peripheral arterial disease in Taiwan. Low HDL-C was defined as < 40 mg/dL for male and < 50 mg/dL for female. The pts with low HDL-C (44%, mean HDL-C 34.9 ± 6.8 mg/dL) during statin treatment were younger and with more female, diabetes, CAD and higher body weight than pts with normal HDL-C. The primary outcome was a composite CV events including CV death, myocardial infarction (MI), stroke or cardiac arrest with resuscitation. The mean follow-up time was 2.7 years. Multivariate Cox proportional hazard analysis showed on-treatment low HDL-C was not an independent risk factor of primary outcome (normal vs. low HDL-C, hazard ratio [HR] 0.82, 95% confidence interval [CI] 0.55-1.20) after adjusting multiple clinical factors. The risk of CV events was recalculated for each quintile of HDL-C. In the univariate model, the CV event rate decreased progressively by 23% from the lowest (< 35 mg/dL) to the highest (> 54 mg/dL) quintile of HDL-C. However, multivariate Cox proportional hazard analysis showed no significant relationships between quintiles of HDL-C levels and the risk of CV events (HDL-C < 35 [HR 1.50, 95% CI 0.82-2.76], 35 to 40.2 [HR 0.99, 95% CI 0.52-1.88], 40.2 to <46 [HR 1.07, 95% CI 0.58-1.99], 46 to < 54 [HR 1.09, 95% CI 0.59-2.01] vs. >54 mg/dL). Conclusions: In Taiwanese pts with ASCVD under statin therapy, low on-treatment HDL-C was not associated with increased risk of CV events. [ABSTRACT FROM AUTHOR]

Aims: To examine the association between statin use before and after intracranial haemorrhage (ICH) and the risk of poststroke epilepsy (PSE)., Methods: Patients with new-onset ICH between 2004 and 2012 were identified from the Taiwan National Health Insurance Research Database. The main outcome was the occurrence of epilepsy after stroke. Multivariable Cox regression modelling was used to estimate the association between statin use and the risk of PSE, with poststroke medication exposures being treated as time-dependent variables., Results: A total of 7435 patients with ICH were enrolled with a median follow-up of 17.6 months. Within the study cohort, 709 patients developed PSE. Poststroke, but not prestroke, stain use was associated with a reduced risk of PSE (adjusted hazard ratio 0.62, 95% confidence interval 0.42-0.90, P = 0.01). In subanalyses, a trend of a dose-response relationship was observed. A significant PSE risk reduction was correlated with a higher cumulative statin dose. Moreover, the risk of PSE was lower in patients receiving moderate-to-high-intensity statin therapy (adjusted hazard ratio 0.37, 95% confidence interval 0.18-0.75, P = 0.01). Lipophilic and hydrophilic statins were similar with regard to their associations with the reduced risk of PSE., Conclusions: Statin therapy may reduce the risk of PSE after ICH, especially with moderate-to-high therapy intensity. Further research is needed to understand the mechanisms underlying the potential protective effects of statins against PSE in this patient population., (© 2018 The British Pharmacological Society.)

Background: Individuals are at increased risk for cardiovascular events following an acute coronary syndrome (ACS). Effective management of hyperlipidemia, an associated risk factor, is essential for improving outcomes. We aimed to quantify the extent of hyperlipidemia and its treatment in ACS survivors in Hong Kong and Taiwan., Methods: The multinational, observational Dyslipidemia International Study (DYSIS) II included patients hospitalized for an ACS. Lipid levels and use of lipid-lowering therapy (LLT) were evaluated at baseline and 4 months post-discharge. The proportions of patients attaining the recommended LDL-C target for individuals at very high cardiovascular risk (<70 mg/dL) was assessed and potential predictors of this outcome evaluated., Results: In total, 270 patients were enrolled, 125 (46.3%) of which were being treated with LLT prior to hospitalization. Of these, 28.8% had an LDL-C level < 70 mg/dL, compared to only 6.9% of those not being treated. Statin monotherapy was the most commonly employed LLT, with a mean atorvastatin-equivalent dosage of 14 mg/day. By 4-month follow-up, target attainment had risen to 45.1% for patients treated with LLT at baseline, and 43.3% for those who had not been treated. LLT was being used by 88.4% of patients at follow-up, with a mean atorvastatin dosage of 18 mg/day. Use of statins in combination with ezetimibe/other non-statin was scarce. No predictors of LDL-C target attainment were identified., Conclusions: In patients hospitalized with an ACS, rates of LDL-C target achievement were poor. While LLT was widely employed, statin intensity was low and combination therapy underused, indicating scope for improvement., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objectives: The objective is to assess the effectiveness of statin use to prevent atrial fibrillation (AF) in dialysis patients., Methods: We used a database from the Registry for Catastrophic Illness from the National Health Research Institute (NHRI), which encompasses almost 100% of the patients receiving dialysis started from 1997 to 2008 in Taiwan. All dialysis patients aged 18 or older without history of cardiovascular events in 1997 and 1998 were incorporated. Finally, 113,191 dialysis patients were enrolled. We used propensity score (PS) matching method and Cox's proportional hazard regression models to estimate hazard ratios for AF events for statin users vs. nonusers., Results: In statin group, the incidence of developing new AF was significantly lower than that in control group (1.1% vs. 3.8%, P<0.001). The PS-based selection process identified 2146 patients receiving statins and 2146 who did not receive statins. The incidence of developing AF remained lower in statin group than that in control group (2.4% vs. 4.9%, P<0.001). After PS matching, Cox's proportional hazard regression analyses showed that there was a protective effect of developing AF in a dose-responsive manner. The protective effect was more obvious in subjects with younger age, female gender, hyperlipidemia, coronary artery disease and peripheral artery disease and in subjects without taking angiotensin converting enzyme inhibitor and angiotensin receptor blocker., Conclusion: Our analyses showed that statin therapy was associated with lower risk of newly diagnosed AF in patients with dialysis., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: This study was to determine the association between the use of statins and the occurrence of peptic ulcer diseases (PUD)., Methods: Using the National Health Insurance Research Database to conduct a population-based cohort study. We identified 48,562 patients who were newly diagnosed with hyperlipidemia during the period of 1998 to 2011 and who were divided into two groups based on their use of statins. The non-statin cohort (without statin treatment, 24,139 patients) were 1:1 frequency matched with sex, age, year of diagnosis of hyperlipidemia and index-year to the statin cohort (24,423 patients). The relative risk of patients with and without statins treatment on the occurrence of PUD and concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin were analyzed using the univariable and multivariable Cox proportional hazards regression model., Results: The incidence of PUD increased with age in both cohorts and female had a higher occurrence rate than male in both cohorts. Compared with the non-statin cohort, the statin cohort was associated with a significant lower risk of PUD for all age group. The concomitant use of aspirin and/or NSAIDs had higher incidence of PUD than those without in both cohorts. Analyzing the cumulative defined daily dose (DDD) of statins indicated that high-dose groups (≧ 575 DDD) exhibited significantly decreased risk compared with non-statin users., Conclusion: The results of the present study indicated that statins might be associated with the protection of peptic ulcer in a dose-respondent manner., (Copyright © 2015 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.)

Aims: Cholangiocarcinoma (CCA) is the second most common primary liver cancer in the world. Due to the lack of effective treatments, the survival rate of CCA is low and it is usually considered difficult to diagnose early. To date, no effective strategies for the prevention of CCA have been developed. Statins are cholesterol-lowering agents which possess pleiotropic properties and the use of statins may reduce cancer risk. The aim of the study was to investigate the effect of statin use on the risk of CCA., Methods: We used nationwide insurance data to perform a case-control study including 3174 CCA patients diagnosed in 2002-2011 and 3174 propensity score matched controls. Odds ratios (ORs) and 95% confidence intervals (CI) were calculated to assess the association between CCA risk and statin use by type of statin and dose., Results: Patients with CCA were slightly younger than controls with mean ages of 67.4 (SD 12.3) and 68.5 (SD 13.2) years (P = 0.001), respectively, and had less users of statins (22.7 vs. 26.5%, P < 0.001). The overall adjusted OR of statin use associated CCA was 0.80 (95% CI 0.71, 0.90) and lowered for those with longer medications. The OR ranged from 0.65 to 0.77. Stronger dose-response association was seen when using lovastatin., Conclusions: Statin use is associated with reduced risk of CCA and there is a dose-response relationship between the use of statins and risk of CCA., (© 2015 The British Pharmacological Society.)

Objectives: The objective of this study was to examine the association between the use of statins and the risk of newly diagnosed dementia in an elderly population., Design, Setting and Participants: Random samples of 1,000,000 individuals covered by the National Health Insurance in Taiwan were included in the analysis. All participants were 65 years or older without dementia and either did or did not start treatment with statins from 1 August 1997 to 31 December 2010. Patients with established dementia before the start of treatment were excluded. Baseline characteristics were matched (by propensity score) in those who did and did not receive statins., Results: A total of 57,669 subjects were included in the analysis with approximately 12 years of follow-up. Propensity score matching identified 2003 patients who received statins and another 2003 patients who did not with comparable baseline characteristics. Adjusted hazard ratios (HRs) for dementia were significantly inversely associated with total or daily equivalent statin dosage (total accumulated dose: HRs 0.829, 0.720 and 0.385 from T1 to T3 vs. control, P < 0.001 for trend; mean daily dose: HRs 0.667, 0.798 and 0.503 from T1 to T3 vs. control, P < 0.001). The results remained robust after propensity adjustment., Conclusion: Independent of traditional risk factors, there was a decrease in newly diagnosed cases of dementia in elderly patients who had received a high total or daily dose of statins. The more potent statins (e.g. atorvastatin and rosuvastatin) seemed to be particularly effective in the prevention of dementia., (© 2014 The Association for the Publication of the Journal of Internal Medicine.)

Background: Recent trials have shown a reduction in the risk of major adverse cardiac events (MACE) with simvastatin-ezetimibe therapy in patients with acute coronary syndrome. The potential benefits of simvastatin-ezetimibe for patients at a lower risk of MACE are unclear. This study aimed to investigate the differences of MACE risk between patients with type 2 diabetes mellitus (DM) using simvastatin-ezetimibe or high potency statins., Methods: This population-based dynamic cohort study used data from the Taiwan National Health Insurance Database. The study subjects were patients with type 2 DM, aged between 40 and 75 years. The simvastatin-ezetimibe group took simvastatin-ezetimibe only, and the statin group took atorvastatin or rosuvastatin but not simvastatin or ezetimibe. The two groups were matched for age, gender, medication date, DM diagnosis date, hypertension, and cardiovascular complications. The outcome variable was new-onset MACE. Univariate and multivariate survival analyses were performed., Results: A total of 20,485 patients (53% male; 4099 in the simvastatin-ezetimibe group and 16,396 in the statin group) were included, with a mean age of 59.1 years. In a total of 37,388 person-years, 1100 patients developed new-onset MACE. The annual incidence rate of new-onset MACE was lower in the simvastatin-ezetimibe group (2.61%) than that in the statin group (3.02%) (p=0.0476). After Cox regression analysis, simvastatin-ezetimibe use was independently associated with a lower risk of MACE (HR, 0.77; 95% confidence interval 0.66-0.90)., Conclusions: Compared to high potency statins alone, simvastatin-ezetimibe therapy was associated with a lower incidence of MACE in patients with type 2 DM., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background/purpose: The relationship between statin use and lung cancer remains unclear. Patients with diabetes mellitus, who are at higher risks for both cancer and atherosclerosis, are usually indicated for statin use. The objective was to explore the relationship between statins, lung squamous cell carcinoma (SCC), and lung adenocarcinoma incidence in diabetic patients., Methods: A cohort of 596,812 type 2 diabetic patients was identified from the Taiwan National Health Insurance claims database in the year 2000, and followed until the earliest of lung cancer diagnosis, death, or December 31, 2007. A Cox regression model with time-varying statin use was applied to estimate the hazard ratio (HR) of lung cancer incidence comparing use and nonuse of statins. A sensitivity analysis was applied to examine the association after adjustment for smoking effect., Results: In the original diabetic cohort, 60,969 statin users and 535,843 statin nonusers were identified. In a median follow-up time of 7.9 years, a total of 1182 incident SCC cases and 2345 adenocarcinoma cases developed. Initial analysis showed a decreased risk of SCC if statins were ever used (HR, 0.69; 95% confidence interval, 0.60-0.81). However, the relative risk would be 0.92 for males and 0.90 for females for statins after adjusting for smoking effect. There was no association between statin use and adenocarcinoma (HR, 0.97; 95% confidence interval, 0.88-1.07), with similar findings after controlling for smoking effect., Conclusion: There is no statistically significant association between statin use with lung cancer incidence in diabetic patients after adjustment for the confounding effect attributed to cigarette smoking., (Copyright © 2013. Published by Elsevier B.V.)

Background: The beneficial effects of statins in patients undergoing hemodialysis are controversial. Our study aimed to investigate the use of statins and the subsequent risk of cardiovascular morbidity and mortality in patients undergoing hemodialysis., Methods: We conducted a cohort study using data from the Taiwan National Health Insurance Research Database. Cox regressions were performed to determine the hazard ratio (HR) of cardiovascular morbidity and mortality in the HD patients taking statins (statin cohort) compared with a propensity-matched comparison cohort., Results: The statin cohort included a total of 4074 patients who received statin treatment while also undergoing hemodialysis (mean age 53.3 ± 13.5 years, male 34.9%). The comparison cohort included 8148 propensity-matched hemodialysis patients who were not using statins. During the three years of follow-up, the statin cohort had lower incidence of ischemic stroke (p < 0.001), hospitalizations due to unstable angina (p < 0.001), deep vein thrombosis (p < 0.001), cardiovascular mortality (p < 0.001), and all-cause mortality (p < 0.001). After Cox regression analysis, statin use was independently associated with lower risk of future ischemic stroke (HR, 0.49; 95% confidence interval [CI], 0.39-0.63), hospitalization for unstable angina (HR, 0.57; 95% CI, 0.47-0.70), deep vein thrombosis (HR, 0.11; 95% CI, 0.05-0.27), cardiovascular mortality (HR, 0.29; 95% CI, 0.18-0.46), and all-cause mortality (HR, 0.49; 95% CI, 0.41-0.58)., Conclusion: Statin use was associated with a lower incidence of cardiovascular morbidity and mortality in patients undergoing hemodialysis., (© 2013.)

In this present study, we found that the use of rosuvastatin with cumulative using duration >12 months could correlate with 2.8-fold increased risk of lung cancer in women. We did not have specific comments on these results. Further prospective clinical studies of statins use are needed to elucidate this issue.

Aim: To investigate whether the use of statins is associated with colorectal cancer risk., Methods: We conducted a population-based case-control study in Taiwan. Data were retrospectively collected from the Taiwan National Health Insurance Research Database. Cases consisted of all patients who were aged 50 years and older and had a first-time diagnosis of colorectal cancer between the period 2005 and 2008. The controls were matched to cases by age, sex, and index date. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multiple logistic regression., Results: We examined 1156 colorectal cancer cases and 4624 controls. The unadjusted ORs for any statin prescription was 1.10 (95% CI = 0.94-1.30) and the adjusted OR was 1.09 (95% CI = 0.91-1.30). When statin use was categorized by cumulative dose, the adjusted ORs were 0.99 (95% CI = 0.78-1.27) for the group with cumulative statin use below 105 defined daily doses (DDDs); 1.07 (95% CI = 0.78-1.49) for the group with cumulative statin use between 106 and 298.66 DDDs; and 1.30 (95% CI = 0.96-1.75) for the group with cumulative statin use of 298.66 DDDs or more compared with nonusers., Conclusion: This study does not provide support for a protective effect of statins against colorectal cancer.