Pharmacoepidemiology Study of Thiazolidinediones on Type II Diabetes Mellitus Patients – Risk Analysis of Cardiovascular Related Adverse Effects
Date Issued
2008
Date
2008
Author(s)
Lin, Yi-shiu
Abstract
Background ardiovascular disease is one of the main causes of death in patients with type II diabetes. Meta-analysis of several clinical trials have raised concerns about increasing risk of myocardial infarction and death from cardiovascular causes in patients treated with rosiglitazone, a drug for diabetes mellitus in the class of thiazolidinedione (TZD). However, a large-scale clinical trial about pioglitazone using time to the occurrence of macrovascular events or death as the primary endpoint focused on has demonstrated a protective effect of pioglitazone on cardiovascular events. Due to lack of national studies examining the effect of TZD on the cardiovascular risk, we conducted the current study to provide a reference for clinical drug safety evaluation and medical policies decision.bjective he study aimed to assess the risk of cardiovascular events between patients who used and who did not use TZD as mono-therapy or combination therapy for DM; and to compare the cardiovascular side effects between rosiglitazone and pioglitazone in order to identify if there was a class effect in the two drugs. ethods his was a retrospective cohort study. We used the National Health Insurance Research Database (NHIRD) to establish a cohort of patients with type 2 diabetes, aged 18 years and older, who initiated any anti-diabetic agents between July 2003 and December 2006. Only patients who didn’t take any antidiabetic agents before were included.escriptive analysis. The two comparison groups: (1) TZD group is defined as those patients who had any claims for TZDs during our study period, and (2) non-TZD group. We compared the pattern of antidiabetic medication use,, demographic and clinical characteristics, and risk factor for CVD events between the two groups. We also compare the difference in prescription pattern between rosiglitazone users and pioglitazone users。nalysis for the relation between TZD use and cardiovascular events. Our primary end point was time to acute myocardial infarction (AMI) and coronary revascularization (CR). Our secondary end points were hospitalizations for stroke or congestive heart failure (CHF). We constructed two time dependent Cox proportional hazards models to evaluate the hazard ratio (HR) of TZD use for each study end points we were interested in. One of the models was constructed to estimate the HR for patients who had ever exposed to TZDs (TZD ever users), and the other one for patients who were current user of TZDs (TZD current user). Because of the different baseline characteristics between the TZD and non-TZD groups, we used the propensity score for the statistic matching to decrease the confounding effects from indication of use. We also conducted statistical analysis to identify the impact of rosiglitazone and pioglitazone on different end points separately.esults A total of 20861 eligible patients were identified from the NHIRD. Compared with the non-TZD group, patients in the TZD group were younger, male dominant, treated with more antidiabetic agents and cardiovascular agents use, and were followed for a longer time. There were different patterns of prescription and clinical characteristics between rosiglitazone users and pioglitazone users. After adjusting several confounding factors, patients exposed to TZDs were more likely than those without to have hospitalization for AMI or CR (HR = 1.47, 95% CI=1.01-2.13, p=0.044). If we analyzed the impact of rosiglitazone and pioglitazone separately, rosiglitazone use was associated with a higher risk for AMI or CR (adjusted HR =1.65, 1.68). There was no significant effect of pioglitazone on risks for AMI or CR. The analyses of baseline characteristics of patients who used rosiglitazone or who suffered from AMI or CR retrospectively revealed that patients treated with rosiglitazone were more likely to be younger, and to use second line oral hypolglycemic agents,and lipid-lowering agents. Cox regression analysis revealed that patients who had higher propensity to use TZDs were more likely to have hospitalization for stroke. TZD current user may be less likely to have stroke event (Adjusted HR = 0.51, 95% CI=0.24-1.08, p=0.08). TZD use had no significant impact on hospitalization for CHF.onclusions Our findings suggest significant differences in demographic and clinical characteristics between the TZD group and the non-TZD group; and significant different prescription patterns between rosiglitazone users and pioglitazone users. Moreover, patients who had ever exposed to TZD, especially rosiglitazone, were at elevated risk of hospitalization for AMI or CR. We recommend that patients who are already in the high risk for ischemic heart disease, who have poor controlled hyperlipidemia may have an additional risk , and should use the rosiglitazone carefully and consider alternative therapies. The current study failed to provide evidence to support an association between TZD use and hospitalization for stroke or HF. It warrants to exam the prediction of TZD to stroke events in further studies according our findings of a marginally significant relationship between TZD and stroke.
Subjects
thiazolidinedione
adverse event
acute myocardial infection
stroke
heart failure
SDGs
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