Association of antidiabetic therapies with lower extremity amputation, mortality and healthcare cost from a nationwide retrospective cohort study in Taiwan.

We compared risks of clinical outcomes, mortality and healthcare costs among new users of different classes of anti-diabetic medications. This is a population-based, retrospective, new-user design cohort study using the Taiwan National Health Insurance Database between May 2, 2015 and September 30, 2017. An individual was assigned to a medication group based on the first anti-diabetic prescription on or after May 1, 2016: SGLT-2 inhibitors, DPP-4 inhibitors, GLP-1 agonists or older agents (metformin, etc.). Clinical outcomes included lower extremity amputation, peripheral vascular disease, critical limb ischemia, osteomyelitis, and ulcer. We built three Cox proportional hazards models for clinical outcomes and mortality, and three regression models with a log-link function and gamma distribution for healthcare costs, all with propensity-score weighting and covariates. We identified 1,222,436 eligible individuals. After adjustment, new users of SGLT-2 inhibitors were associated with 73% lower mortality compared to those of DPP-4 inhibitors or users of older agents, while 36% lower total costs against those of GLP-1 agonists. However, there was no statistically significant difference in the risk of lower extremity amputation across medication groups. Our study suggested that SGLT-2 inhibitors is associated with lower mortality compared to DPP 4 inhibitors and lower costs compared to GLP-1 agonists.

Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Bare Metal Stent Implantation: A Nationwide Cohort Study.

BACKGROUND: To investigate whether there is an increased risk of cardiovascular (CV) events in patients with diabetes associated with adding proton pump inhibitors (PPIs) to clopidogrel (CLO) therapy after bare-metal stent (BMS) deployment. METHODS: We used the National Health Insurance Research Database to conduct this retrospective cohort study. We enrolled 6,757 patients with diabetes who underwent BMS deployment and received CLO with/without PPIs for 90 days (6,243 in the CLO subgroup and 514 in the CLO plus PPI subgroup). The endpoints were acute coronary syndrome and re-admission for revascularization (PCI or coronary artery bypass graft surgery) after 3, 6, and 12 months. RESULTS: The patients who received CLO with PPIs had no significant increase in adverse CV events compared to those without PPIs within 1 year after BMS deployment [3-month hazard ratio (HR) = 0.87, 95% confidence interval (CI), 0.65-1.15; 6 months, HR = 0.95, 95% CI, 0.78-1.15; 1 year, HR = 0.60, 95% CI, 0.81-1.12]. CONCLUSIONS: In patients with diabetes undergoing BMS deployment, there was no evidence of an increased risk of CV events among concomitant users of CLO and PPIs. Our results indicate that the use of PPIs may not modify the protective effect of CLO after BMS implantation.

Epidemiology of psoriatic disease and current treatment patterns from 2003 to 2013: A nationwide, population-based observational study in Taiwan.

BACKGROUND: Recent global data show an increasing prevalence of psoriasis and psoriatic arthritis in western countries. OBJECTIVE: The current study analyzed the trend of prevalence rates of psoriasis and psoriatic arthritis in Taiwan and examined biologic prescription patterns by different specialties. METHODS: Data were accessed from the national payer National Health Insurance Research Database in Taiwan. This study protocol was approved by Joint Institutional Review Board established by Medical Research Ethics Foundation (No 13-S-001). RESULTS: Between 2003 and 2013, the prevalence of psoriasis and psoriatic arthritis increased by 41% (from 15.54 to 21.90 per 10,000 population) and 191% (from 0.45 to 1.31 per 10,000 population), respectively, while the prevalence of psoriatic arthritis among patients with psoriatic disease increased from 6.3% to 12.7%. Dermatologists are the main caregivers for patients with psoriasis and psoriatic arthritis; however, data suggest a decreasing trend in the proportion of dermatologists for psoriasis patients from 24.7% between 2003 and 2008 to 10.74% between 2008 and 2013, with a corresponding decrease in dermatologists for psoriatic arthritis patients from 62.30% to 44.65% during the same periods, respectively. In 2013, of the 51,191 patients with psoriasis, only 596 (1.16%) received biologics (73.3% by dermatologists and 25.8% by rheumatologists), while 1120 of the 7470 (14.99%) psoriatic arthritis patients received biologics (72.8% by rheumatologists and 22.3% by dermatologists). The proportion of biologics use was 1.12% and 7.75% among all patients with only psoriasis and 8.01% and 26.70% among all patients with psoriatic arthritis seen by dermatologists and rheumatologists, respectively. CONCLUSION: The prevalence of psoriasis and psoriatic arthritis is increasing in Taiwan. The use of biologics in patients with psoriatic arthritis was comparable to that reported in previous studies in the United States and Europe; however, the use of biologics remained low in patients with psoriasis in Taiwan.

The Risk of Chronic Pancreatitis in Patients with Psoriasis: A Population-Based Cohort Study.

BACKGROUND: Psoriasis is a chronic systemic inflammatory disorder, and studies have revealed its association with a variety of comorbidities. However, the risk of chronic pancreatitis (CP) in psoriasis has not been studied. This study aimed to investigate the risk of CP among patients with psoriasis. METHODS: Using the Taiwan National Health Insurance Research Database, this population-based cohort study enrolled 48430 patients with psoriasis and 193720 subjects without psoriasis. Stratified Cox proportional hazards models were used to compare the risks of CP between the patients with and without psoriasis. RESULTS: The incidence of CP was 0.61 per 1000 person-years in patients with psoriasis and 0.34 per 1000 person-years in controls during a mean 6.6-year follow-up period. Before adjustment, patients with psoriasis had a significantly higher risk of CP (crude hazard ratio (HR) = 1.81; 95% confidence interval (CI) = 1.53-2.15), and the risk remained significantly higher after adjustments for gender, age group, medications, and comorbidities (adjusted HR (aHR) = 1.76; 95% CI = 1.47-2.10). All psoriasis patient subgroups other than those with arthritis, including those with mild and severe psoriasis and those without arthritis, had significantly increased aHRs for CP, and the risk increased with increasing psoriasis severity. Psoriasis patients taking nonsteroidal anti-inflammatory drugs (aHR = 0.33; 95% CI = 0.22-0.49) and methotrexate (aHR = 0.28; 95% CI = 0.12-0.64) had a lower risk of developing CP after adjustments. CONCLUSIONS: Psoriasis is associated with a significantly increased risk of CP. The results of our study call for more research to provide additional insight into the relationship between psoriasis and CP.

Concomitant Sleep Disorders Significantly Increase the Risk of Cardiovascular Disease in Patients with Psoriasis.

BACKGROUND: The increased rates of cardiovascular morbidity and mortality in patients with psoriasis are not adequately explained by traditional risk factors. Whether concomitant sleep disorders (SDs) modify the risk of cardiovascular disease (CVD) in patients with psoriasis remains unknown. METHODS: Using the Taiwan National Health Insurance Research Database (NHIRD), we conducted a cohort study to investigate the association between concomitant SDs and CVD risk in patients with psoriasis. Data from 99,628 adults who received a psoriasis diagnosis during the period from 2004 to 2010 were analyzed. Cox proportional hazards regression analysis models were used to compare the risks of ischemic heart disease (IHD) and stroke between patients with and without SDs. RESULTS: Psoriasis patients with a concomitant SD had significantly higher risks of IHD (adjusted hazard ratio [aHR], 1.25; 95% confidence interval [CI], 1.22-1.28) and stroke (aHR, 1.24; 95% CI, 1.16-1.33) as compared with psoriasis patients without SDs. All psoriasis patient subgroups, including those with mild and severe psoriasis and those with and without arthritis, had increased HRs for IHD and stroke. The increases in IHD and stroke risks conferred by SDs were proportional to the dose of hypnotics used. The effect of SDs on the risks of IHD and stroke was greater in young adults than in middle-aged and older adults. CONCLUSIONS: The risks of IHD and stroke were higher for psoriasis patients with SDs than for those without SDs. Clinicians should carefully evaluate CVD risk, particularly in young patients with psoriasis.

Effects of Clopidogrel and Proton Pump Inhibitors on Cardiovascular Events in Patients with Type 2 Diabetes Mellitus after Drug-Eluting Stent Implantation: A Nationwide Cohort Study.

OBJECTIVE: To investigate whether there is an increased risk of cardiac events in diabetic patients with a combined therapy of clopidogrel (CLO) and proton pump inhibitors (PPIs) after drug-eluting stent (DES) deployment. METHODS: By using National Health Insurance Research Database, all patients who received CLO with or without PPI therapy within 90 days after undergoing DES (limus-eluting or paclitaxel-eluting stents) deployment were enrolled. Endpoints were acute coronary syndrome (ACS) and readmission for revascularization (percutaneous coronary intervention or coronary artery bypass graft surgery) after 3, 6, and 12 months. RESULTS: A total of 6,603 diabetic patients received LESs (5,933 in the CLO subgroup and 670 in the CLO plus PPIs subgroup), and 3,202 patients received PESs (2,923 in the CLO subgroup and 279 in the CLO plus PPIs subgroup). The patients who received CLO plus PPIs were at higher risk of ACS than those receiving CLO within 1 year after DES deployment (LESs: 6-month hazard ratio [HR] = 1.63, and 1-year HR = 1.37; PESs: 3-month HR = 1.72). Patients with a history of ACS who received CLO plus PPIs were at higher risk of ACS after LES implantation (HR = 1.55) than those in the CLO group. CONCLUSION: In "real-world" diabetic patients with LES deployment, the combination of PPIs and CLO is associated with higher rates of ACS after 6 months and 1 year. Even after correction for confounding factors, concomitant PPI use remained an independent predictor of cardiac events, emphasizing the clinical importance of this drug-drug interaction.

Anti-diabetic therapies and the risk of acute pancreatitis: a nationwide retrospective cohort study from Taiwan.

AIMS: To examine the relationship between different anti-diabetic therapies (dipeptidyl peptidase-4 (DPP-4), metformin and sulfonylureas) and risk of acute pancreatitis among type 2 diabetic patients in Taiwan, and explore each drug's dose-response relationship. MATERIALS AND METHODS: We derived a nationwide retrospective cohort of patients with type 2 diabetes in Taiwan. The inclusion criteria are adult diabetic patients with continuous baseline enrollment, new users of the studied drugs, and without missing demographics. There were 4113/101 498/44 772 DPP-4/Metformin/Sulfonylurea users. Adjusted hazards ratios for pancreatitis associated with DPP-4, derived from Cox proportional hazard models with propensity score weighting, were estimated; dose-response analyses were also conducted. RESULTS: Dipeptidyl peptidase-4 was statistically significantly associated with a decreased risk of acute pancreatitis compared with sulfonylureas (adjusted HR: 0.36, 95%CI [0.17, 0.75]) but not metformin (adjusted HR: 0.67, 95%CI [0.32, 1.41]); metformin was statistically significantly associated with a lower risk of pancreatitis than sulfonylurea (adjusted HR: 0. 53; 95%CI [0.37, 0.76]). In addition, low-dose metformin was statistically significantly associated with a lower risk of pancreatitis compared with high-dose metformin (HR: 0.65; 95%CI [0.44, 0.97]). CONCLUSIONS: Our findings suggest that sulfonylureas may potentially be associated with an increased risk of pancreatitis compared with DPP-4 or metformin. Studies with longer follow up, larger sample sizes, and more precise capture of confounders may be needed to determine the risk of pancreatitis associated with incretin based therapies.

Effects of thiazolidinediones on cardiovascular events in patients with type 2 diabetes mellitus after drug-eluting stent implantation: a retrospective cohort study using the national health insurance database in Taiwan.

BACKGROUND: Thiazolidinediones (TZDs) may reduce in-stent restenosis and improve clinical outcomes in type 2 diabetic patients after bare-metal stent implantation. However, it is still unknown whether diabetic patients with drug-eluting stents (DESs) could benefit from treatment with TZDs. OBJECTIVE: The objective was to evaluate the clinical outcomes of TZDs in type 2 diabetic patients within 1 year of receiving DESs. METHODS: This retrospective cohort study was performed in 1743 Taiwanese type 2 diabetic patients (1137 men; 606 women) who received DESs between December 1, 2006 and December 31, 2007. Patients were classified into TZD (n = 268) or non-TZD groups (n = 1,475) using medication records within 3 months of the index hospitalization. Follow-up data were available through December 31, 2008. Clinical outcome measurements included death, myocardial infarction (MI), and repeat revascularization within 1 year after the index date of hospitalization. Cox proportional hazards model and other analyses were performed for the study. RESULTS: For the TZD and non-TZD groups, the mean ages were 65.07 and 66.09 years, respectively, for those with limus-eluting stents (LESs) and 65.61 and 65.81 years, respectively, for those with paclitaxel-eluting stents (PESs). With or without TZD medication, there were no significant differences in the adjusted hazard ratios of death, MI, or repeat revascularization for diabetic patients who received LESs or PESs. TZD treatment in patients who received LESs and had a history of MI was associated with a higher risk of MI (hazard ratio = 5.292; 95% CI, 1.028-27.232). CONCLUSIONS: TZDs did not improve the clinical outcomes in Taiwanese type 2 diabetes patients who received DESs. TZDs might have been a contributor to higher risk of MI in patients with LESs and a history of MI. Larger clinical trials are still needed to study this issue further.

Alendronate and raloxifene use related to cardiovascular diseases: differentiation by different dosing regimens of alendronate.

BACKGROUND: Bisphosphonates are the class of medication used most widely to treat osteoporosis. Since an article reported that patients who used zoledronic acid, a bisphosphonate, had a higher proportion of atrial fibrillation (AF) in 2007, the issue of bisphosphonates and AF has become a growing concern. Due to the widespread use of bisphosphonates, it is necessary to explore the relationship between bisphosphonates and AF and other cardiovascular diseases. OBJECTIVE: We aimed to investigate the risk of AF, stroke, or acute myocardial infarction (AMI) associated with the use of the bisphosphonates alendronate and raloxifene in patients with osteoporosis. We also focused our analysis on the impact of different dosing regimens of alendronate. METHODS: The National Health Insurance Research Database was used to conduct an 8-year, population-based, retrospective cohort study. The study population comprised women who first took alendronate or raloxifene between 2002 and 2006 and who had a history of osteoporosis and vertebral or spinal fracture. Follow-up was conducted for every patient until the first diagnosis of AF, stroke, or AMI or until the end of the 1-year follow-up period. The Cox proportional hazards model was used to evaluate the association between the risk of cardiovascular disease and the prescription of alendronate or raloxifene. RESULTS: We identified 9609 women who had been prescribed either alendronate (n = 6949) or raloxifene (n = 2660). The patients treated with alendronate were at a lower risk of AF, stroke, or AMI compared with the raloxifene group (AF: hazard ratio [HR] = 0.60 [95% CI, 0.42-0.85]; stroke: HR = 0.47 [95% CI, 0.39-0.57]; AMI: HR = 0.51 [95% CI, 0.36-0.72]). However, when analyzing the groups by different alendronate dosing regimens, those patients who received alendronate 10 mg had a significantly higher risk of AF and stroke compared with patients who received raloxifene (AF: HR = 1.66 [95% CI, 1.12-2.46]; stroke: HR = 1.56 [95% CI, 1.23-1.98]). The alendronate 70-mg group demonstrated a lower risk of cardiovascular disease, be it AF, stroke, or AMI (AF: HR = 0.28 [95% CI, 0.18-0.43]; stroke: HR = 0.23 [95% CI, 0.18-0.30]; AMI: HR = 0.28 [95% CI, 0.18-0.41]). When we assigned alendronate 10 mg as the reference group, the alendronate 70 mg group had a lower risk of 3 cardiovascular diseases (AF: HR = 0.17 [95% CI, 0.10-0.27]; stroke: HR = 0.16 [95% CI, 0.12-0.22]; AMI: HR = 0.21 [95% CI, 0.13-0.35]). CONCLUSIONS: Alendronate 10 mg was associated with a higher risk of cardiovascular disease than alendronate 70 mg. Further studies are required to investigate this relationship.