The impact of the rare disease and Orphan Drug Act in Taiwan.

The Rare Disease and Orphan Drug Act (the Act) was enacted in 2000 in Taiwan for the facilitation of the research, development, and accessibility of orphan drugs and special nutritional foods; for the prevention and early diagnosis of rare diseases; and for providing intensive care for patients with rare diseases. The aim was to investigate the impact of the Act on the availability and use of orphan drugs in Taiwan in the hope of identifying the remaining challenges and possible solutions to assist future policy making, which may be applicable in other countries as well. The information and statistics for rare diseases and orphan drugs retrieved from the official annual reports and documents were analyzed. There were 225 diseases recognized as rare diseases, and one-third (75/225) of them were congenital metabolic disorders. Among the 110 designated orphan drugs that could apply for listing in the National Health Insurance (NHI) Pharmaceutical Benefits and Reimbursement Scheme, approximately half (62/110) of them were granted marketing authorization. While the NHI program compulsory for all citizens increased patient accessibility to orphan drugs, the rapidly increasing economic burden became an urgent issue for the government. Emerging gene therapies may be the solution to unmet medical needs and also a financial obstacle to tackle. The Act increased the availability of orphan drugs while the NHI system facilitated patient access, which benefited many patients with rare diseases in Taiwan. However, the soaring economic burden was noticed and was anticipated to aggravate. More communication and cooperation between stakeholders is critical in finding solutions for the long-term sustainability of the NHI system.

Psoriasis is associated with a greater risk for cardiovascular procedure and surgery in patients with hypertension: A nationwide cohort study.

Psoriasis increases the incidence of hypertension and cardiovascular disease. However, its effect on the course of cardiovascular disease remains unknown. To investigate whether patients with psoriasis and hypertension have a higher requirement for cardiovascular procedure and surgery than patients with hypertension but without psoriasis, we used the Taiwan National Health Insurance Research Database to identify patients with new-onset hypertension during 2005-2006. Among these patients, those with psoriasis (n = 4039) were matched in a 1:1 ratio by age and sex with patients without psoriasis. The association between psoriasis and cardiovascular interventions was examined using time-varying Cox proportional hazards models. The mean follow-up period was 5.62 years. Psoriasis was associated with an increased risk for cardiovascular procedure and surgery in patients with hypertension (adjusted hazard ratio [aHR], 1.28; 95% confidence interval [CI], 1.07-1.53). When no psoriasis served as a reference group, the aHRs were higher for women than for men, and for patients aged 50-64 years than for younger and older patients. Patients with severe psoriasis or psoriatic arthritis tended to have higher risks of cardiovascular procedure and surgery than patients with mild psoriasis (aHR, 1.22; 95% CI, 0.98-1.51) or patients without psoriatic arthritis (aHR, 1.15; 95% CI, 0.84-1.58), respectively, did, although not reaching statistical significance. In conclusion, patients with hypertension and psoriasis had a greater requirement for cardiovascular interventions than hypertensive patients without psoriasis. More intense assessments for cardiovascular interventions may be necessary in patients with concurrent hypertension and psoriasis than general hypertension patients.

Increased risk of avascular necrosis in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Avascular necrosis (AVN) and psoriasis have some pathogenic mechanisms and associated conditions in common. OBJECTIVE: To examine the association between psoriasis and AVN. METHODS: This study used data from the Taiwan National Health Insurance Research Database for the period 2004-2006 and identified 28,268 patients with psoriasis, who were then matched for age and sex with 113,072 controls without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Multivariate Cox proportional hazards models were used for the analysis. RESULTS: The unadjusted risk of AVN was significantly higher for patients with psoriasis than for controls (hazard ratio [HR] 2.29) and remained significant after adjustment for other risk factors (adjusted HR 1.96; 95% confidence interval 1.62-2.38). The risk for AVN increased in relation to psoriasis severity and was higher for patients with psoriasis and arthritis than for patients without arthritis. The adjusted HRs were higher for male patients than for female patients and for patients younger than 30 years compared with older patients. LIMITATIONS: We lacked information on daily tobacco use, alcohol consumption, and physical activity. CONCLUSION: The risk for AVN increased with the disease severity of psoriasis.

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.

Increased risk of aortic aneurysm (AA) in relation to the severity of psoriasis: A national population-based matched-cohort study.

BACKGROUND: Inflammation of systemic and vascular tissues besides the skin in psoriasis is associated with cardiovascular morbidity and mortality. OBJECTIVE: We sought to investigate whether or not patients with psoriasis have an increased risk of aortic aneurysm (AA). METHODS: This population-based cohort study identified 34,301 patients with psoriasis in the Taiwan National Health Insurance Research Database during 2004 to 2006, who were matched for age and sex with 137,204 control subjects without psoriasis from the Taiwan Longitudinal Health Insurance Database 2000. Each individual was individually followed up for 5 years to identify those who subsequently developed AA. RESULTS: After adjusting for medical history and medication use, patients with psoriasis were at increased overall risk of AA (adjusted hazard ratio [HR] 1.80; 95% confidence interval 1.25-2.61). The risk for AA increased with the severity of psoriasis. The adjusted HRs were higher for male than female patients (adjusted HR 1.84 vs 1.56), and for patients younger than 50 years versus older patients (adjusted HR 2.81 vs 1.64). LIMITATIONS: There is a lack of information regarding patients' Psoriasis Area and Severity Index score, daily tobacco use, or alcohol consumption. CONCLUSION: Patients with psoriasis are predisposed to developing AA: this risk increases with psoriasis severity and is independent of established cardiovascular risk factors.

Risk of fractures in vitiligo patients treated with phototherapy-A retrospective population-based cohort study.

BACKGROUND: Phototherapy might increase bone mineral density. However, it is unknown whether phototherapy can reduce the risk of fractures in patients with vitiligo. OBJECTIVES: To investigate the effect of phototherapy on fracture risks in vitiligo patients aged 40 or older. METHODS: This population-based cohort study used the 2000-2010 Taiwan National Health Insurance Research Database (NHIRD) to identify 3863 patients newly diagnosed with vitiligo between 2003 and 2009 at age ≥40 years. Study subjects were classified into three cohorts: (1) frequent phototherapy; (2) infrequent phototherapy; and (3) no phototherapy. Patients were followed until the first hip or vertebral fracture or 31 December 2010. Data were analysed using Cox regression models and also stratified by age and gender. RESULTS: Frequent phototherapy decreased the fracture risks (adjusted hazard ratio (aHR)=0.32, p=0.009) in vitiligo patients. Stratification by age and gender confirmed the fracture prevention effect of frequent phototherapy in patients aged 40-64 years (aHR=0.14, p=0.016) and in female patients (aHR=0.31, p=0.024). CONCLUSIONS: This study provides the first evidence that frequent phototherapy can reduce the risk of fractures among middle-aged and among female vitiligo patients.

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.

Increased risk of arrhythmia in patients with psoriatic disease: A nationwide population-based matched cohort study.

BACKGROUND: Psoriasis is associated with cardiovascular morbidity and mortality. However, the association between psoriasis and arrhythmia has not been adequately studied. OBJECTIVE: We sought to investigate whether patients with psoriasis have an increased risk of arrhythmia. METHODS: This population-based cohort study identified 40,637 patients with psoriasis and 162,548 subjects without psoriasis matched by age, sex, history of coronary artery disease, hypertension, and diabetes in the Taiwan National Health Insurance Research Database during 2004 through 2006. RESULTS: After adjusting for medical history and medication use, patients with psoriasis were at increased risk of overall arrhythmia (adjusted hazard ratio [aHR] 1.34; 95% confidence interval [CI] 1.29-1.39). The risks of arrhythmia were higher in all subgroups, including patients with severe (aHR 1.25; 95% CI 1.12-1.39) and mild (aHR 1.35; 95% CI 1.30-1.41) psoriasis, and in patients with (aHR 1.46; 95% CI 1.22-1.74) and without (aHR 1.33; 95% CI 1.28-1.39) psoriatic arthritis. LIMITATIONS: The National Health Insurance Research Database did not contain information regarding Psoriasis Area and Severity Index, cigarette smoking, or alcohol consumption. CONCLUSION: Patients with psoriasis were at higher risk of developing arrhythmia, particularly for those with psoriatic arthritis, independent of traditional cardiovascular risk factors.

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.

Risk-adjusted resource allocation: using Taiwan's National Health Insurance as an example.

OBJECTIVES: To determine if access to medical services differed by regions and to demonstrate the extent of the differences of adopting a claims-based risk-adjustment system versus a demographic model for regional resource allocation. METHODS: The claims of a 1% random sample of Taiwan's National Health Insurance enrollees (N = 173 175) in 2002 was used. The number of visits and morbidity-adjusted resource consumption were calculated individually then collapsed regionally. Regional expected resource allocation was compared with actual consumption. RESULTS: After controlling for diagnosis-based health measures, the average numbers of visits were stable across regions. Two models were consistent in showing over- or underutilization; the overall difference between two models in resource allocation was 5.8% at the district level. We observed strong urban overutilization and rural underutilization. CONCLUSIONS: Access to medical services is similar across regions. The adoption of a diagnosis-based model over a demographic-adjusted budgeting method would affect resource allocation considerably.

Safety of deferasirox: a retrospective cohort study on the risks of gastrointestinal, liver and renal events.

BACKGROUND: Deferasirox (DFX) is an effective and well-tolerated oral iron chelator elevating the adherence to iron chelating therapy among patients with iron overload. However, the US Food and Drug Administration issued a warning about the potential adverse events associated with DFX in 2010. METHODS: To examine the risks of gastrointestinal (GI) bleeding, acute liver necrosis, and acute renal failure among DFX users compared with desferrioxamine (DFO) users in a real-world setting, first-time users of DFX or DFO between 2005 and 2008 in Taiwan's National Health Insurance database were observed in this population-based retrospective cohort study. The risks of different adverse events were individually analyzed by Cox proportional hazards models and adjusted by age, sex, concomitant medications, and prior medical conditions. RESULTS: Deferasirox users had the highest incidence rates of GI bleeding (2.03 per 10 000 patient-days), acute liver necrosis (0.26 per 10 000 patient-days) and acute renal failure (1.45 per 10 000 patient-days) compared with other iron chelator users. Compared with DFO users, DFX users were not associated with the risk of GI bleeding (adjusted HR 1.03, 95% CI 0.61-1.74, p = 0.90) and the risk of acute liver necrosis (adjusted HR 2.13, 95% CI 0.49-9.33, p = 0.32). The association between DFX use and acute renal failure was found to be statistically significant (HR 2.18, 95% CI 1.18-4.02, p = 0.01; adjusted HR 2.41, 95% CI 1.27-4.58, p = 0.01). CONCLUSION: In this study, we found statistically significant higher risk of acute renal failure and non-statistically significant higher risk of GI bleeding and acute liver necrosis associated with DFX use. More researches are warranted to evaluate the association between DFX use and potential adverse events.

Risk of bladder cancer in diabetic patients treated with rosiglitazone or pioglitazone: a nested case­control study.

BACKGROUND: Evidence has emerged that pioglitazone may increase the risk of bladder cancer, but the association has not been confirmed. This potential risk also has not been evaluated in users of rosiglitazone. OBJECTIVE: Using Taiwan's National Health Insurance Research Database (NHIRD), this large population-based nested case­control study was conducted to explore the relationship between the use of rosiglitazone or pioglitazone and risk of bladder cancer in diabetic patients. METHODS: We identified 3,412 cases of newly diagnosed bladder cancer and 17,060 controls (1:5 matched by age and sex) among a diabetic patient cohort from the NHIRD.We defined an index date for each case as the date of first hospitalization for bladder cancer. Each control was assigned the index date of their corresponding case. Multivariable conditional logistic regressions were used to estimate the association between exposure (timing and duration) to rosiglitazone or pioglitazone and bladder cancer. We defined rosiglitazone or pioglitazone exposure as ''current'' if the prescription duration covered the index date or ended at 90 days before, as ''recent'' if it ended 91­180 days before the index date, or as ''past'' if the last prescription ended more than 180 days before. Duration of rosiglitazone or pioglitazone use was defined based on the cumulative days of exposure prior to the index date: < 1, 1­2 and ≥ 2 years. RESULTS: Rosiglitazone and pioglitazone use were associated with risk of bladder cancer and the associations were stronger with a longer term of exposure (pioglitazone < 1 year odds ratio [OR] 1.45 [95 % CI 1.12­1.87, p < 0.01], 1­2 years OR 1.74 [95 % CI 1.05­2.90, p = 0.03] and ≥ 2 years OR 2.93 [95 % CI 1.59­5.38, p < 0.01]; rosiglitazone < 1 year OR 0.98 [95 % CI0.82­1.17, p = 0.81], 1­2 years OR 1.78 [95 % CI 1.31­2.39, < 0.01] and ≥ 2 years OR 2.00 [95 % CI 1.37­2.92, p < 0.01]). CONCLUSIONS: Long-term exposures to pioglitazone and rosiglitazone were associated with higher odds of bladder cancer, and the highest odds were seen in users with ≥ 2 years of exposure.

Clinical outcomes of vertebroplasty or kyphoplasty for patients with vertebral compression fractures: a nationwide cohort study.

OBJECTIVE: To evaluate the outcome of vertebroplasty or kyphoplasty (VK), in comparison with non-VK treatment, among patients hospitalized for first-ever vertebral compression fractures (VCFs). DESIGN: A population-based retrospective cohort study. SETTING: Taiwan' s National Health Insurance claims data. PARTICIPANTS: All individuals aged ≥ 60 years who were newly discharged after hospitalization for a primary VCF diagnosis. INTERVENTION: Percutaneous vertebroplasty or kyphoplasty. MEASUREMENTS: Study outcomes were discharge outcome (re-hospitalization within 1 week, 1 month or 6 months, categorized by diagnosis) and the prescription of anti-osteoporosis medication for secondary fracture prevention. Potential selection bias was adjusted by using propensity score matching to select one conservatively treated patient (e.g. lumbar brace, analgesics, or physical therapy) matched to one patient receiving VK. RESULTS: The study cohort consisted of 9238 patients who had been discharged after hospitalization for a first-ever VCF between 2004 and 2007. During the index hospitalization, 1018 patients received VK, compared with 8,220 patients who did not receive VK. Patients receiving percutaneous procedure group had a consistently lower incidence of 7-day re-hospitalization for any of the three outcomes (OR = 0.48; 95% CI: 0.32-0.72). Considering the cause of re-hospitalization separately, the vertebroplasty/kyphoplasty group had a significantly lower risk of 7-day re-hospitalization for fracture-related diagnosis (OR = 0.28, 95% CI: 0.12-0.68) and musculoskeletal diagnosis (OR = 0.08, 95% CI: 0.01-0.88) as well as a significantly lower risk of 1-month re-hospitalization (OR = 0.74; 95% CI: 0.59-0.93). CONCLUSIONS: VK may protect patients with VCFs from short-term re-hospitalization and a greater need exists for anti-osteoporosis medication as secondary prevention for this at-risk patient group.

Health characteristics of older people who rotationally live with families: a nationwide survey.

BACKGROUND: Population aging has been a critical issue around the world and people will have to face living problems when they get old. In Western countries, older people are more used to live alone or in institutions. In Eastern countries, due to filial piety of Chinese culture, the elderly prefer to live with their children or their relatives. There was no empirical study to investigate the relationship between health and living arrangement among older Taiwanese. OBJECTIVE: This study was designed to explore the association between living arrangement and health characteristics among the elderly in Taiwan. METHOD: This study used national representative data from the Taiwan Longitudinal Study on Aging surveyed in 2007. We identified 2621 elders aged older than 65 in 2007 and categorized them into 3 types of living arrangement by the questionnaire. Linear regressions were used to analyze the relationship between living arrangement and health status (activities of daily living [ADLs], instrumental activities of daily living [IADLs], and Center of Epidemiological Studies-depression [CES-D]) among the elderly. RESULTS: Elderly individuals who indicated they rotationally lived with family members had poorer health conditions, including IADLs (Coeff = 0.23; 95% confidence interval [CI]: -0.06-0.52) and CES-D (Coeff = 0.41; 95% CI: -0.59-1.40), than those who steadily lived with family. In contrast, elderly individuals who lived alone had better health conditions in IADLs (Coefficient = -0.38; 95% CI: -0.53 to -0.22) than those who indicated they lived steadily with family. CONCLUSIONS: These findings reveal that this type of rotational living is not a good living arrangement for the elderly.

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.

Hip and subtrochanteric or diaphyseal femoral fractures in alendronate users: a 10-year, nationwide retrospective cohort study in Taiwanese women.

BACKGROUND: A link between the use of alendronate and atypical diaphyseal femoral fracture has been suggested. OBJECTIVE: The goal of this study was to evaluate the benefits of alendronate in preventing rehospitalization due to hip fractures and whether its use increases risk of hospitalization for atypical diaphyseal femoral fractures in Taiwan. METHODS: Using Taiwan's National Health Insurance database, we identified women with osteoporosis with a first-ever hospitalization for vertebral or hip fractures between 2001 and 2007, which consisted of all patients receiving alendronate, raloxifene, calcitonin salmon, or teriparatide after the index fracture hospitalization. Data of untreated women were obtained as the untreated cohort. Study outcomes were defined as a rehospitalization due to hip fracture or a new hospitalization for subtrochanteric or diaphyseal femoral fracture. RESULTS: Among 11,278 women identified (mean age, 77 years), 2425 (21.5%) received alendronate, 2694 (23.9%) received other antiosteoporosis drugs, and 6159 (54.6%) were untreated. Patients in each group were comparable in fracture history and major comorbidities; untreated patients were more likely to have stroke (11.2%; P = 0.01) and those treated with alendronate were more likely to have a history of hyperlipidemia (16.2%; P = 0.03). Compared with the untreated patient cohort, our analysis suggested that patients prescribed alendronate were associated with decreased risk of rehospitalization due to hip fracture (hazard ratio = 0.67 [95% CI, 0.54-0.82]). Neither patients prescribed alendronate, nor those prescribed other antiosteoporosis drugs, differed significantly from the untreated patient cohort in terms of risk of hospitalization for atypical femoral fracture (adjusted hazard ratios = 0.77 and 0.49 [95% CI, 0.40-1.47 and 0.22-1.12], respectively). Consistent with these data, short- or long-term alendronate use was not found to be significantly associated with higher risk of atypical femoral fractures. CONCLUSIONS: This study in Taiwanese patients suggests that alendronate use was associated with a reduction in risk of rehospitalization due to hip fracture. We did not find a significant association between alendronate use and risk of hospitalization for atypical femoral fracture.

Relationship between cardiovascular outcomes and proton pump inhibitor use in patients receiving dual antiplatelet therapy after acute coronary syndrome.

BACKGROUND: There is conflicting evidence regarding the potential interaction between clopidogrel and proton pump inhibitors (PPIs), with observational studies suggesting an increased risk of adverse cardiovascular (CV) outcomes and clinical trials suggesting there is no such risk. METHODS: We conducted a retrospective cohort study to assess CV outcomes of 9753 patients taking dual antiplatelet therapy of aspirin plus clopidogrel with or without a PPI after hospitalization for acute coronary syndrome (ACS). Cox proportional hazards models were used to assess our primary endpoint of re-hospitalization for ACS in overall sample and a propensity score matching subsample. RESULTS: Among patients taking clopidogrel plus aspirin, concomitant use of PPI was not associated with the risk of re-hospitalization for ACS (adjusted hazard ratio [HR] 1.12 [95%CI 0.72-1.73]). The findings were consistent in the propensity score matching cohort (adjusted HR 0.82 [95%CI 0.43-1.54]). Compared with PPI nonusers, there is no significant association between each specific PPI users and the risk of re-hospitalization for ACS (adjusted HR; omeprazole 0.96 [95%CI 0.35-2.66], pantoprazole 1.05 [95%CI 0.38-2.92], rabeprazole 0.60 [95%CI 0.17-2.17], esomeprazole 0.31 [95%CI 0.10-0.99], and lansoprazole 0.82 [95%CI 0.32-2.07]). CONCLUSION: In conclusion, this population-based cohort study found that concomitant use of clopidogrel and PPI in patients who received dual antiplatelet therapy after ACS was not associated with risk of ACS re-hospitalization. Together, our study and findings of recently published clinical trials suggest that there was no apparent CV interaction between clopidogrel and PPI in patients who received dual antiplatelet therapy.

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.