Chi-Feng Hsieh

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.

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.

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.

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.

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.

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.

The patterns of outpatient off‐label carbamazepine use and the potential impact of regulatory labelling process in Taiwan

Background  Carbamazepine has been associated with severe cutaneous adverse drug reactions (ADR). It is important for patients with these ADRs under off‐label prescriptions are not eligible for drug injury relief in Taiwan. We conducted a study to depict the demography and possible factors related to the off‐label carbamazepine use in Taiwan. We also explored the policy influence of carbamazepine use.