Association between extent of thiazolidinedione exposure and risk of acute myocardial infarction.
OBJECTIVE
To determine if an association exists between thiazolidinedione (rosiglitazone or pioglitazone) exposure and acute myocardial infarction, and if the timing of drug initiation relative to the onset of myocardial infarction affected the frequency of the event.


METHODS
Nested, case-control study.


METHODS
Health care claims from California, Florida, New York, Ohio, and Illinois from the Medicaid Analytic Extract database for calendar years 2001-2002.


METHODS
Of patients who received metformin plus a sulfonylurea during a defined eligibility period, we identified 2316 cases who had a primary discharge diagnosis of acute myocardial infarction and 9700 controls, who were defined by means of risk-set sampling.


RESULTS
We reviewed demographic and clinical characteristics of the cases and controls, and documented initiation of thiazolidinedione therapy. We noted the time of therapy initiation within 180 days of the index date (date of acute myocardial infarction for cases, same date for matched controls) and assessed any association between the start of thiazolidinedione therapy and acute myocardial infarction, relative to use of metformin plus a sulfonylurea. We performed secondary analyses using various time intervals between start of thiazolidinedione and onset of event (0-90 and 91-180 days before the index date). Applying conditional logistic regression, we obtained adjusted odds ratios (AORs) and 95% confidence intervals (CIs). After adjustment for confounding, starting rosiglitazone (AOR 1.00, 95% CI 0.72-1.39) or pioglitazone (AOR 1.04, 95% CI 0.74-1.45) therapy in the 180 days before the index date was not associated with acute myocardial infarction. Point estimates for rosiglitazone (AOR 1.29, 95% CI 0.85-1.94) and, less so, pioglitazone (AOR 1.15, 95% CI 0.73-1.81) in the 90 days before the index date suggested a small increase in the rate of acute myocardial infarction shortly after the start of these drugs; however, the CIs were wide.


CONCLUSIONS
Starting thiazolidinedione therapy was not associated with acute myocardial infarction. However, our data did not exclude the possibility of elevated risk immediately after beginning therapy. Clinicians should be cautious when prescribing thiazolidinediones, especially rosiglitazone, for patients at high risk for having an acute myocardial infarction.
Dore
David D
DD
i3 Drug Safety, Waltham, Massachusetts 02451, USA. david.dore@i3drugsafety.com
Trivedi
Amal N
AN
Mor
Vincent
V
Lapane
Kate L
KL
D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016208:Databases, Factual; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D000077205:Pioglitazone; D012306:Risk; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage / Q000009:adverse effects*; D013997:Time Factors; D014481:United States / Q000453:epidemiology
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone