Rosiglitazone and myocardial infarction in patients previously prescribed metformin.
OBJECTIVE
Rosiglitazone was found associated with approximately a 43% increase in risk of acute myocardial infarction (AMI) in a two meta-analyses of clinical trials. Our objective is to estimate the magnitude of the association in real-world patients previously treated with metformin.


METHODS
We conducted a nested case control study in British Columbia using health care databases on 4.3 million people. Our cohort consisted of 158,578 patients with Type 2 diabetes who used metformin as first-line drug treatment. We matched 2,244 cases of myocardial infarction (AMI) with up to 4 controls. Conditional logistic regression models were used to estimate matched odds ratios for AMI associated with treatment with rosiglitazone, pioglitazone and sulfonylureas.


RESULTS
In our cohort of prior metformin users, adding rosiglitazone for up to 6 months was not associated with an increased risk of AMI compared to adding a sulfonylurea (odds ratio [OR] 1.38; 95% confidence interval [CI], 0.91-2.10), or compared to adding pioglitazone (OR for rosi versus pio 1.41; 95% CI, 0.74-2.66). There were also no significant differences between rosiglitazone, pioglitazone and sulfonylureas for longer durations of treatment. Though not significantly different from sulfonylureas, there was a transient increase in AMI risk associated with the first 6 months of treatment with a glitazone compared to not using the treatment (OR 1.53; 95% CI, 1.13-2.07)


CONCLUSIONS
In our British Columbia cohort of patients who received metformin as first-line pharmacotherapy for Type 2 diabetes mellitus, further treatment with rosiglitazone did not increase the risk of AMI compared to patients who were treated with pioglitazone or a sulfonylurea. Though not statistically significantly different compared from each other, an increased risk of AMI observed after starting rosiglitazone or sulfonylureas is a matter of concern that requires more research.
Dormuth
Colin R
CR
Therapeutics Initiative, University of British Columbia, Vancouver, Canada. colin.dormuth@ti.ubc.ca
Maclure
Malcolm
M
Carney
Greg
G
Schneeweiss
Sebastian
S
Bassett
Ken
K
Wright
James M
JM
D000368:Aged; D016022:Case-Control Studies; D015331:Cohort Studies; D048909:Diabetes Complications / Q000175:diagnosis*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D008297:Male; D016347:Medical Records Systems, Computerized; D008687:Metformin / Q000009:adverse effects* / Q000627:therapeutic use*; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000150:complications / Q000209:etiology*; D000077205:Pioglitazone; D012044:Regression Analysis; D012306:Risk; D000077154:Rosiglitazone; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use*
D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D008687:Metformin; D000077205:Pioglitazone