Antithyroid drug-related hepatotoxicity in hyperthyroidism patients: a population-based cohort study.

AIMS: The evidence of hepatotoxicity of antithyroid drugs (ATDs) is limited to case reports or spontaneous reporting. This study aimed to quantify the incidence and comparative risks of hepatotoxicity for methimazole (MMI)/carbimazole (CBM) vs. propylthiouracil (PTU) in a population-based manner. METHODS: We conducted a cohort study of hyperthyroidism patients initially receiving MMI/CBM or PTU between 1 January 2004 and 31 December 2008 using the Taiwan National Health Insurance Research Database. The examined hepatotoxicity consisted of cholestasis, non-infectious hepatitis, acute liver failure and liver transplant, with the incidences and relative risks being quantified by Poisson exact methods and Cox proportional hazard models, respectively. RESULTS: The study cohort comprised 71 379 ATD initiators, with a median follow-up of 196 days. MMI/CBM vs. PTU users had a higher hepatitis incidence rate (3.17/1000 vs. 1.19/1000 person-years) but a lower incidence of acute liver failure (0.32/1000 vs. 0.68/1000 person-years). The relative risk analysis indicated that any use of MMI/CBM was associated with a 2.89-fold (95% CI 1.81, 4.60) increased hepatitis risk compared with PTU, with the risk increasing to 5.08-fold for high dose MMI/CBM (95% CI 3.15, 8.18). However, any MMI/CBM use vs. PTU was not related to an increased risk of cholestasis (adjusted hazard ratio [HR] 1.14, 95% CI 0.40, 3.72) or acute liver failure (adjusted HR 0.54, 95% CI 0.24, 1.22). CONCLUSIONS: MMI/CBM and PTU exert dissimilar incidence rates of hepatotoxicity. Compared to PTU, MMI/CBM are associated in a dose-dependent manner with an increased risk for hepatitis while the risks are similar for acute liver failure and cholestasis.

Use of antipsychotics and risk of venous thromboembolism in postmenopausal women. A population-based nested case-control study.

Despite continued uncertainty of venous thromboembolism (VTE) caused from antipsychotic agents, this safety issue has not been examined in postmenopausal women, a population with high usages of antipsychotics and at high risk for VTE. We assessed whether antipsychotic use was associated with an increased VTE risk in women after menopause. We conducted a nested case-control study of all Taiwanese women aged ≥ 50 years (n = 316,132) using a nationwide healthcare claims database between 2000 and 2011. All newly diagnosed VTE patients treated with an anticoagulant or thrombectomy surgery were identified as cases (n = 2,520) and individually matched to select controls (n = 24,223) by cohort entry date, age, cancer diagnosis and major surgery procedure. The odds ratios (ORs) and 95 % confidence interval (CI) of VTE associated with antipsychotics were estimated by multivariate conditional logistic regressions. Current use of antipsychotics was associated with a 1.90-fold (95 % CI = 1.64-2.19) increased VTE risk compared with nonuse in postmenopausal women. The VTE risk existed in a dose-dependent fashion (test for trend, p<0.001), with a more than quadrupled risk for high-dose antipsychotics (adjusted OR = 4.60; 95 % CI = 2.88-7.33). Current parenteral administration of antipsychotics also led to a 3.46-fold increased risk (95 % CI = 2.39-5.00). Conversely, there was no increased VTE risk when antipsychotics were discontinued for > 30 days. In conclusion, current use of antipsychotics is significantly associated with a dose-dependent increased risk of VTE in postmenopausal women, especially for those currently taking high-dose or receiving parenteral antipsychotics.

Antidepressant use and risk of recurrent stroke: a population-based nested case-control study.

OBJECTIVE: Antidepressants may carry an increased risk for incident stroke, but there is little safety evidence regarding poststroke antidepressant use. This study aimed to examine whether antidepressants are associated with an increased risk of stroke recurrence. METHOD: A population-based nested case-control study was conducted analyzing the Taiwan universal health care claims database from January 1, 2000, to December 31, 2008. We followed up 19,825 patients who survived a first admission for stroke at the age of ≥ 18 years, among which 3,536 hospitalized cases with stroke recurrence (ICD-9-CM codes 430.xx-437.xx) were identified and individually matched to 6,679 randomly-selected controls. Multivariate conditional logistic regression models were used to characterize the risk associated with antidepressant use. RESULTS: The study cohort had a mean age of 66 years and was followed up for a median of 2.9 person-years. Use of any tricyclic antidepressants (TCAs) was associated with a 1.41-fold (95% CI, 1.19-1.67) increased risk of stroke recurrence, whereas any use of selective serotonin reuptake inhibitors (SSRIs) or other antidepressants showed no association. Stopping TCAs for 1-30 days was associated with a 1.87-fold (95% CI, 1.22-2.86) increased risk of stroke recurrence, and the risk was attenuated for a longer discontinuation. The stroke risk associated with TCA use was not present in a dose-dependent or duration-dependent manner. CONCLUSIONS: Use of TCAs, but not SSRIs or other antidepressants, was associated with an increased risk of stroke recurrence. The risk is particularly elevated with abrupt cessation of TCA therapy. Health care professionals should be vigilant to that risk during TCA therapy in poststroke patients.

Statin use and risk of COPD exacerbation requiring hospitalization.

BACKGROUND: Despite recent studies that suggested statins' beneficial effects on chronic obstructive pulmonary disease (COPD) outcomes, the impact, if any, of statins on COPD exacerbations remains unclear. This study aimed to examine the association between statin use and risk of hospitalized COPD exacerbation, and to assess whether the association varied by statin initiation, dose, or duration of use. METHODS: A retrospective nested case-control study among patients with COPD was conducted analyzing a nationwide health insurance claims database in Taiwan. Cases were subjects hospitalized for COPD exacerbations; each case was matched to 4 randomly selected controls on age, sex, cohort entry, and number of COPD-related outpatient visits by an incident-density sampling approach. Conditional logistic regressions were employed to quantify the COPD exacerbation risk associated with statin use. RESULTS: The study cohort comprised 14,316 COPD patients, from which 1584 cases with COPD exacerbations and 5950 matched controls were identified. Any use of statins was associated with a 30% decreased risk of COPD exacerbation (95% confidence interval [CI], 0.56-0.88), and current use of statins was related to a greater reduced risk (adjusted odds ratio [OR] 0.60; 95% CI, 0.44-0.81). A dose-dependent reduced risk of COPD exacerbation by statins was observed (medium average daily dose: adjusted OR 0.60; 95% CI, 0.41-0.89; high daily dose: adjusted OR 0.33; 95% CI, 0.14-0.73). The reduced risk remained significant for either short or long duration of statin use. CONCLUSIONS: Statin use was associated with a reduced risk of COPD exacerbation, with a further risk reduction for statins prescribed more recently or at high doses.