Thiazolidinediones and heart failure: a teleo-analysis.
OBJECTIVE
Thiazolidinediones (TZDs) are known to increase the risk of heart failure in patients with type 2 diabetes. We aimed to evaluate the magnitude of the risk of heart failure with TZDs and classify this adverse effect under the novel dose-time-susceptibility system.


METHODS
Evidence from randomized trials, controlled observational studies, anecdotal case reports, case series, and spontaneous reports in the Canadian Drug Reaction Monitoring Program (CADRMP) was analyzed in a teleo-analysis.


RESULTS
A random-effects meta-analysis of three randomized controlled trials showed an odds ratio (OR) of 2.1 (95% CI 1.08-4.08; P = 0.03) for the risk of heart failure in patients randomized to TZDs compared with placebo. Four observational studies revealed an OR of 1.55 (1.33-1.80; P < 0.00001) for heart failure with TZDs. A dose-time-susceptibility analysis of 28 published reports and 214 spontaneous reports from the CADRMP database showed that heart failure was more likely to occur after several months (with median treatment duration of 24 weeks after initiation of therapy). Heart failure equally occurred at high and low doses. The adverse reaction was not limited to the elderly, with 42 of 162 (26%) of the reported cases occurring in patients aged <60 years.


CONCLUSIONS
Our teleo-analysis confirms the increased magnitude of the risk of heart failure with TZDs. We estimate the number needed to harm with TZDs to be approximately 50 over 2.2 years. Existing guidelines and package inserts may have to be revised to incorporate these risk characteristics of TZDs.
Singh
Sonal
S
Section of General Internal Medicine, Wake Forest University School of Medicine, 1 Medical Center Blvd., Winston-Salem, NC 27157, USA. sosingh@wfubmc.edu
Loke
Yoon K
YK
Furberg
Curt D
CD
D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D003925:Diabetic Angiopathies / Q000139:chemically induced; D004198:Disease Susceptibility; D006333:Heart Failure / Q000139:chemically induced*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D016017:Odds Ratio; D016032:Randomized Controlled Trials as Topic; D045162:Thiazolidinediones / Q000009:adverse effects*
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones