Fei-Yuan Hsiao

Effect of polypharmacy, potentially inappropriate medications and anticholinergic burden on clinical outcomes: a retrospective cohort study

Background: Polypharmacy, potentially inappropriate medications and anticholinergic burden (as assessed by the anticholinergic risk scale) are commonly used as quality indicators of pharmacotherapy in older adults. However, their role in clinical practice is undefined. We sought to investigate longitudinal changes in these indicators and their effects on clinical outcomes. Methods: We used Taiwan’s Longitudinal Health Insurance Database to retrieve quarterly information about drug use for people aged 65 years and older over a 10-year period. We analyzed the association between indicators and all-cause admission to hospital, fracture-specific admission to hospital and death using generalized estimating equations. Results: The study cohort comprised 59 042 older adults (65–74 yr: 39 358 [66.7%], 75–84 yr: 16 903 [28.6%], and ≥ 85 yr: 2781 [4.7%]). The mean changes in polypharmacy over the course of the study were greatest among patients aged 65–74 years (absolute difference +2.14, 95% confidence interval [CI] 2.10–2.19), then among those aged 75–84 yr (+1.79, 95% CI 1.70–1.88), and finally those aged 85 years and older (+0.71, 95% CI 0.36–1.05). The number of potentially inappropriate medications increased among patients aged 65–74 years (+0.16 [0.15–0.18]) and 75–84 years (+0.09 [0.06–0.08]), but decreased in those aged 85 years and older (−0.15 [−0.26 to −0.04]). Polypharmacy, potentially inappropriate medications and anticholinergic risk scale were each associated with an increased risk of admission to hospital, but not with death. In addition, both polypharmacy (5–9 drugs: odds ratio [OR] 1.18, 95% CI 1.12–1.24; ≥ 10 drugs: OR 1.54, 95% CI 1.42–1.66) and anticholinergic burden (score 1–2: 1.39, 95% CI 1.31–1.48; ≥ 3: 1.53, 95% CI 1.41–1.66) showed dose–response relations with fracture-specific admission to hospital. Interpretation: The total number of drugs taken (polypharmacy), number of potentially inappropriate medications and anticholinergic risk changed during follow-up and varied across age groups in this cohort of older adult patients. These indicators showed dose–response relations with admission to hospital, but not with death.

Thiazolidinediones and cardiovascular events in patients with type 2 diabetes mellitus: a retrospective cohort study of over 473,000 patients using the National Health Insurance database in Taiwan.

AbstractBackground and objective: Concern has been expressed over the cardiovascular risks associated with rosiglitazone and pioglitazone. This study investigates the association between oral antihyperglycaemics (rosiglitazone, pioglitazone, sulfonylureas and metformin) with myocardial infarction, congestive heart failure, angina pectoris, stroke and transient ischaemic attack. Methods: We used Taiwan’s 2000–5 National Health Insurance database to conduct a population-based, retrospective cohort study of 473 483 newly diagnosed patients with type 2 diabetes mellitus. We classified study patients into five basic groups based on the agents they were prescribed during the study period: (i) rosiglitazone monotherapy; (ii) pioglitazone monotherapy; (iii) sulfonylurea-based therapy; (iv) metformin-based therapy; and (v) sulfonylurea and metformin-based therapy. Cox proportional hazards models were used to evaluate the association between the use of rosiglitazone or pioglitazone and the occurrence of cardiovascular events. Results: Patients receiving rosiglitazone monotherapy were at higher risk for any cardiovascular event (hazard ratio [HR] 1.89; 95% CI 1.57, 2.28), myocardial infarction (HR 2.09; 95% CI 1.36, 3.24), angina pectoris (HR 1.79; 95% CI 1.39, 2.30) and transient ischaemic attack (HR 2.57; 95% CI 1.33, 4.96) than those receiving metformin monotherapy. Overall, add-on rosiglitazone and pioglitazone were associated with comparable cardiovascular risk. Based on our point estimates, pioglitazone as an add-on therapy was found to have a favourable, but nonsignificant, effect on outcome. Conclusions: Our findings extend the evidence from current literature to a real-world setting and support data from clinical trials that the disadvantages or harm caused by thiazolidinediones, especially rosiglitazone, may outweigh their benefits in patients with type 2 diabetes.

Osteoporosis treatment and atrial fibrillation: alendronate versus raloxifene.

Objectives: Concerns have been raised about bisphosphonate use and risk of atrial fibrillation (AF) in women with osteoporosis. This study compares the risk of AF and of flutter or acute myocardial infarction (AMI) in women with osteoporosis taking alendronate or raloxifene. Methods: Using Taiwans National Health Insurance database to conduct a population-based retrospective cohort study, we reviewed the medical and prescription histories of 27,257 women with osteoporosis (21,037 receiving alendronate and 6,220 receiving raloxifene) between 2001 and 2007. Mean (SD) follow-up was 303.62 (422.87) days. For the main outcome measures, we calculated the adjusted relative risk of AF and AMI using the Cox proportional hazards model, adjusting for various confounders. Results: Incidence rates (per patient-year) of AF in the alendronate group (1.00%) and the raloxifene group (1.02%) were similar. Alendronate use was not associated with risk of AF (hazard ratio [HR], 1.06; 95% CI, 0.85-1.32) and AMI (HR, 1.02; 95% CI, 0.86-1.19) compared with raloxifene use. However, alendronate users who had previous cardiovascular events and had taken their medications for more than 1 year were at significantly greater risk of AMI than were the group taking raloxifene (HR, 2.24; 95% CI, 1.07-4.71). Users who received 70 mg of alendronate once a week were at significantly lower risk of AF than were those taking 10 mg daily (HR, 0.56; 95% CI, 0.47-0.68). Conclusions: Compared with raloxifene, alendronate did not increase the risk of AF and flutter in women with osteoporosis. Medical history contributed most to the development of AF or AMI in the women who received either raloxifene or alendronate. Long-term treatment with alendronate is not suggested for women with a history of cardiovascular events because they are at increased risk of AMI.

A comparison of aspirin and clopidogrel with or without proton pump inhibitors for the secondary prevention of cardiovascular events in patients at high risk for gastrointestinal bleeding

OBJECTIVE This study was conducted to compare the risk of recurrent hospitalization for major gastrointestinal (GI) complications (peptic ulcer, bleeding, and perforation) in patients at high GI risk who require ongoing antiplatelet therapy (aspirin [acetylsalicylic acid] or clopidogrel) with or without proton pump inhibitors (PPIs). METHODS This population-based, retrospective cohort study employed data from the Taiwanese National Health Insurance database (January 2001 through December 2006) for patients who had a history of hospitalization for GI complications before the initiation of antiplatelet therapy with aspirin or clopidogrel. Recurrent hospitalizations for major GI complications were analyzed using a Cox proportional hazards model, with adjustment for age, sex, ulcer-related medical history, ulcer-related risk factors, and use of ulcer-related medications during follow-up. The propensity score method was applied to adjust for selection bias. RESULTS The analysis included data from 14,627 patients (12,001 receiving aspirin, 2626 receiving clopidogrel). The incidence of recurrent hospitalization for major GI complications was 0.125 per person-year in aspirin users, 0.103 per person-year in users of aspirin plus a PPI, 0.128 per person-year in clopidogrel users, and 0.152 per person-year in users of clopidogrel plus a PPI. Among aspirin users, those taking PPIs had a significantly lower adjusted risk of hospitalization for major GI complications than did non-PPI users (hazard ratio [HR] = 0.76; 95% CI, 0.64-0.91). Use of a PPI was not associated with a significant risk reduction among clopidogrel users (HR = 1.08; 95% CI, 0.89-1.33). An adjusted survival curve for the risk of recurrent hospitalization for major GI complications indicated that the risk increased numerically faster in clopidogrel users compared with those using aspirin plus a PPI, although the mean drug cost per person-year was 5.08 times higher in clopidogrel users than in users of aspirin plus a PPI. CONCLUSIONS In this analysis in patients at high GI risk who were receiving antiplatelet therapy for the secondary prevention of cardiovascular events, aspirin plus a PPI was associated with a reduced risk of recurrent hospitalization for major GI complications. This was not the case for clopidogrel plus a PPI.

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 Taiwans 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

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.

Thiazolidinediones and cardiovascular events in patients with type 2 diabetes mellitus: a retrospective cohort study of over 473000 patients using the national health insurance database in Taiwan

AbstractBackground and objective: Concern has been expressed over the cardiovascular risks associated with rosiglitazone and pioglitazone. This study investigates the association between oral antihyperglycaemics (rosiglitazone, pioglitazone, sulfonylureas and metformin) with myocardial infarction, congestive heart failure, angina pectoris, stroke and transient ischaemic attack. Methods: We used Taiwan’s 2000–5 National Health Insurance database to conduct a population-based, retrospective cohort study of 473 483 newly diagnosed patients with type 2 diabetes mellitus. We classified study patients into five basic groups based on the agents they were prescribed during the study period: (i) rosiglitazone monotherapy; (ii) pioglitazone monotherapy; (iii) sulfonylurea-based therapy; (iv) metformin-based therapy; and (v) sulfonylurea and metformin-based therapy. Cox proportional hazards models were used to evaluate the association between the use of rosiglitazone or pioglitazone and the occurrence of cardiovascular events. Results: Patients receiving rosiglitazone monotherapy were at higher risk for any cardiovascular event (hazard ratio [HR] 1.89; 95% CI 1.57, 2.28), myocardial infarction (HR 2.09; 95% CI 1.36, 3.24), angina pectoris (HR 1.79; 95% CI 1.39, 2.30) and transient ischaemic attack (HR 2.57; 95% CI 1.33, 4.96) than those receiving metformin monotherapy. Overall, add-on rosiglitazone and pioglitazone were associated with comparable cardiovascular risk. Based on our point estimates, pioglitazone as an add-on therapy was found to have a favourable, but nonsignificant, effect on outcome. Conclusions: Our findings extend the evidence from current literature to a real-world setting and support data from clinical trials that the disadvantages or harm caused by thiazolidinediones, especially rosiglitazone, may outweigh their benefits in patients with type 2 diabetes.

Cardiovascular events associated with long-term use of celecoxib, rofecoxib and meloxicam in Taiwan : An observational study

AbstractBackground: Using national data (2001–2003), this study explored the risk of acute myocardial infarction (AMI), angina, stroke and transient ischaemic attack (TIA) in long-term users of rofecoxib and celecoxib in Taiwan and compared this data with that for those using meloxicam. Methods: Patients included in the study had used celecoxib, rofecoxib or meloxicam for at least 180 days. Data were taken from National Health Insurance database for the period from 2001 to 2003. Main outcome measurements were the occurrence of AMI, angina, stroke or TIA after the initiation of long-term continuous use of these drugs. Person-time exposures and hazard ratios (HRs) were calculated based on data from 9602 eligible patients. Results: In patients without a history of a cardiovascular event within the year before drug treatment began, the overall rates of AMI, angina, stroke and TIA were 1.1%, 0.6%, 2.0% and 0.6%, respectively. In those with cardiovascular events in the year before treatment began, the overall rates of AMI, angina, stroke and TIA were 5.0%, 4.8%, 6.6% and 5.8%, respectively. Compared with meloxicam users, celecoxib users had lower HRs for the development of AMI (HR 0.78, 95% CI 0.63, 0.96) and stroke (HR 0.81, 95% CI 0.70, 0.93). Rofecoxib users were at no higher risk of cardiovascular events than those receiving meloxicam. Regardless of treatment, having had a cardiovascular event in the year before treatment began played a significant role in the development of the same cardiovascular event during the prescription period; the HRs associated with having had the same cardiovascular event in the past year, versus not having had such an event, were 3.02 (95% CI 1.44, 6.32) for AMI, 5.82 (95% CI 3.19, 10.63) for angina, 2.44 (95% CI 1.79, 3.33) for stroke and 7.16 (95% CI 3.70, 13.87) for TIA. Conclusions: Patients taking celecoxib had a lower risk of cardiovascular events than those taking meloxicam. Patients taking rofecoxib were not found to be at higher cardiovascular risk than those taking meloxicam. The most significant determinant of cardiovascular risk was a history of such cardiovascular disease in the year preceding treatment initiation. Patients with a history of other medical conditions also appeared to be at higher risk of adverse cardiovascular events.

Risk of hospitalization and healthcare cost associated with Diabetes Complication Severity Index in Taiwan's National Health Insurance Research Database ,

OBJECTIVE The aim of this study is to test the validity of adapted Diabetes Complication Severity Index (aDCSI) in predicting the risk of hospitalization and healthcare cost in type 2 diabetic patients using a nationally-representative claims database. STUDY DESIGN Retrospective cohort study used 4years of claims data from Taiwans National Health Insurance Research Database (NHIRD). METHODS Type 2 diabetic patients who had 4-years of enrollment were identified as study subjects (N=136,372). The aDCSI score (sum of diabetic complication with severity levels, range 0-13) and complication count (sum of diabetic complications, range 0-7) were generated using diagnostic codes for each patient. Poisson model and linear regression model were conducted to predict risk of hospitalization and healthcare costs associated with aDCSI score and count of diabetic complications. RESULTS The aDCSI score (risk ratio 1.51 to 10.32 categorically, and 1.41 linearly) and count of diabetic complications (risk ratio 1.56 to 12.20 categorically, and 1.66 linearly) were significantly positively associated with risk of hospitalization. A one-point increase in the aDCSI score was positively associated with increased healthcare costs. CONCLUSIONS The performance of aDCSI in predicting risk of hospitalization and healthcare cost in the nationally-representative claims database is similar to those reported in the original study. It may serve as an efficient tool for stratifying type 2 diabetic patients for disease management programs and population-based studies.

Comparative Effectiveness of Different Chemotherapeutic Regimens on Survival of People Aged 66 and Older with Stage III Colon Cancer:: A Real World Analysis Using Surveillance, Epidemiology, and End Results-Medicare Data

OBJECTIVES: To compare the effectiveness and utilization trends of irinotecan (IRI)‐based and oxaliplatin (OX)‐based regimens with those of 5‐fluorouracil and leucovorin (5FU/LV) alone in people aged 66 and older with Stage III colon cancer.