Thiazolidinediones and Cardiovascular Outcomes in Older Patients With Diabetes

Institute of Health Policy, Management and Evaluation, University of Toronto, Toronto, Ontario, Canada
JAMA The Journal of the American Medical Association (Impact Factor: 35.29). 01/2008; 298(22):2634-43. DOI: 10.1001/jama.298.22.2634
Source: PubMed


Thiazolidinediones (TZDs), used to treat type 2 diabetes, are associated with an excess risk of congestive heart failure and possibly acute myocardial infarction. However, the association between TZD use and cardiovascular events has not been adequately evaluated on a population level.
To explore the association between TZD therapy and congestive heart failure, acute myocardial infarction, and mortality compared with treatment with other oral hypoglycemic agents.
Nested case-control analysis of a retrospective cohort study using health care databases in Ontario. We included diabetes patients aged 66 years or older treated with at least 1 oral hypoglycemic agent between 2002 and 2005 (N = 159 026) and followed them up until March 31, 2006.
The primary outcome consisted of an emergency department visit or hospitalization for congestive heart failure; secondary outcomes were an emergency department visit or hospitalization for acute myocardial infarction and all-cause mortality. The risks of these events were compared between persons treated with TZDs (rosiglitazone and pioglitazone) and other oral hypoglycemic agent combinations, after matching and adjusting for prognostic factors.
During a median follow-up of 3.8 years, 12 491 patients (7.9%) had a hospital visit for congestive heart failure, 12,578 (7.9%) had a visit for acute myocardial infarction, and 30 265 (19%) died. Current treatment with TZD monotherapy was associated with a significantly increased risk of congestive heart failure (78 cases; adjusted rate ratio [RR], 1.60; 95% confidence interval [CI], 1.21-2.10; P < .001), acute myocardial infarction (65 cases; RR, 1.40; 95% CI, 1.05-1.86; P = .02), and death (102 cases; RR, 1.29; 95% CI, 1.02-1.62; P = .03) compared with other oral hypoglycemic agent combination therapies (3478 congestive heart failure cases, 3695 acute myocardial infarction cases, and 5529 deaths). The increased risk of congestive heart failure, acute myocardial infarction, and mortality associated with TZD use appeared limited to rosiglitazone.
In this population-based study of older patients with diabetes, TZD treatment, primarily with rosiglitazone, was associated with an increased risk of congestive heart failure, acute myocardial infarction, and mortality when compared with other combination oral hypoglycemic agent treatments.

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    • "Thiazolidinones, belongs to an important group of heterocyclic compounds, which have been extensively explored for their pharmacological applications. These compounds are known to exhibit a wide variety of biological activities such as antibacterial [1] [2], antitubercular [3], anticancer [4], Antidiabetic [5] , insecticidal [6] herbicidal [7], anthelmatics [8], cardiovascular [9], antiviral [10], hypnotic [11] [12] [13], antifungal [14] [15] [16], antitumor [17], anticonvulsant [18], local anesthetic [19] and antimicrobial [20] [21] etc. "

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    • "While there may be a beneficial effect of TZDs in asthma, it is also important to note TZDs have been associated with multiple adverse effects, including weight gain and heart failure, bladder cancer (in the case of pioglitzone) and possible cardiovascular effects (in the case of rosiglitazone) [33-35]. These adverse effects would have to be weighed against any potential gain in asthma management. "
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    ABSTRACT: Background Thiazolidinediones are oral diabetes medications that selectively activate peroxisome proliferator-activated receptor gamma and have potent anti-inflammatory properties. While a few studies have found improvements in pulmonary function with exposure to thiazolidinediones, there are no studies of their impact on asthma exacerbations. Our objective was to assess whether exposure to thiazolidinediones was associated with a decreased risk of asthma exacerbation. Methods We performed a cohort study of diabetic Veterans who had a diagnosis of asthma and were taking oral diabetes medications during the period of 10/1/2005 – 9/30/2006. The risk of asthma exacerbations and oral steroid use during 10/1/2006 – 9/30/2007 was compared between patients who were prescribed thiazolidinediones and patients who were on alternative oral diabetes medications. Multivariable logistic regression and negative binomial regression analyses were used to characterize this risk. A sensitivity analysis was performed, restricting our evaluation to patients who were adherent to diabetes therapy. Results We identified 2,178 patients who were on thiazolidinediones and 10,700 who were not. Exposure to thiazolidinediones was associated with significant reductions in the risk of asthma exacerbation (OR = 0.79, 95% CI, 0.62 – 0.99) and oral steroid prescription (OR = 0.73, 95% CI 0.63 – 0.84). Among patients who were adherent to diabetes medications, there were more substantial reductions in the risks for asthma exacerbation (OR = 0.64, 95% CI 0.47 – 0.85) and oral steroid prescription (OR = 0.68, 95% CI 0.57 – 0.81). Conclusions Thiazolidinediones may provide a novel anti-inflammatory approach to asthma management by preventing exacerbations and decreasing the use of oral steroids.
    Full-text · Article · Jul 2014 · Allergy Asthma and Clinical Immunology
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    • "More debated remain the association between TZD use and cardiovascular events. In a case-control study of a cohort of 159,026 patients aged ≥ 66 years, TZD therapy (primarily rosiglitazone) was reported to be associated with increased risk of congestive hearth failure, acute myocardial infarction and death as compared to other oral hypoglycemic agents [153]. These results have not been confirmed in other studies [154] while an observational study suggested that TZDs were not associated with increased mortality for cardiac events and congestive heart failure in older patients [155]. "
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    ABSTRACT: Type 2 diabetes mellitus (T2DM) is one of the most common chronic disorders in older adults and the number of elderly diabetic subjects is growing worldwide. Nonetheless, the diagnosis of T2DM in elderly population is often missed or delayed until an acute metabolic emergency occurs. Accumulating evidence suggests that both aging and environmental factors contribute to the high prevalence of diabetes in the elderly. Clinical management of T2DM in elderly subjects presents unique challenges because of the multifaceted geriatric scenario. Diabetes significantly lowers the chances of "successful" aging, notably it increases functional limitations and impairs quality of life. In this regard, older diabetic patients have a high burden of comorbidities, diabetes-related complications, physical disability, cognitive impairment and malnutrition, and they are more susceptible to the complications of dysglycemia and polypharmacy. Several national and international organizations have delivered guidelines to implement optimal therapy in older diabetic patients based on individualized treatment goals. This means appreciation of the heterogeneity of the disease as generated by life expectancy, functional reserve, social support, as well as personal preference. This paper will review current treatments for achieving glycemic targets in elderly diabetic patients, and discuss the potential role of emerging treatments in this patient population.
    Full-text · Article · Mar 2014 · Aging
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