Relationship between thiazolidinedione use and cardiovascular outcomes and all-cause mortality among patients with diabetes: a time-updated propensity analysis.
OBJECTIVE
To investigate the association of the thiazolidinediones (TZDs), rosiglitazone, and pioglitazone, together and individually on the risk of cardiovascular outcomes and all-cause mortality, using time-updated propensity score adjusted analysis.


METHODS
We conducted a retrospective cohort study in a large vertically integrated health system in southeast Michigan. Cohort inclusion criteria included adult patients with diabetes treated with oral medications and followed longitudinally within the health system between 1 January 2000 and 1 December 2006. The primary outcome was fatal and non-fatal acute myocardial infarction (AMI). Secondary outcomes included hospitalizations for congestive heart failure (CHF), fatal, and non-fatal cerebrovascular accidents (CVA) and transient ischemic attacks (TIA), combined coronary heart disease (CHD) events, and all-cause mortality.


RESULTS
19,171 patients were included in this study. Use of TZDs (adjusted hazard ratio (aHR) with propensity adjustment (PA), 0.92; 95% confidence interval (CI) 0.73-1.17), rosiglitazone (aHR with PA, 1.06; 95%CI 0.66-1.70), and pioglitazone (aHR with PA, 0.91; 95%CI 0.69-1.21) was not associated with a higher risk of AMI. However, pioglitazone use was associated with a reduction in all-cause mortality (aHR with PA, 0.60; 95%CI 0.42-0.96). Compared with rosiglitazone, pioglitazone use was associated with a lower risk of all outcomes assessed, particularly CHF (p = 0.013) and combined CHD events (p = 0.048).


CONCLUSIONS
Our findings suggest that pioglitazone may have a more favorable risk profile when compared to rosiglitazone, arguing against a singular effect for TZDs on cardiovascular outcomes.
Habib
Zeina A
ZA
Department of Internal Medicine, Henry Ford Hospital, Detroit, MI 48202, USA.
Tzogias
Leonidas
L
Havstad
Suzanne L
SL
Wells
Karen
K
Divine
George
G
Lanfear
David E
DE
Tang
Jeffrey
J
Krajenta
Richard
R
Pladevall
Manel
M
Williams
L Keoki
LK
D000208:Acute Disease; D002318:Cardiovascular Diseases / Q000401:mortality; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D018450:Disease Progression; D004359:Drug Therapy, Combination; D005260:Female; D006760:Hospitalization / Q000706:statistics & numerical data*; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality*; D000077205:Pioglitazone; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D000077154:Rosiglitazone; D020521:Stroke / Q000401:mortality; D045162:Thiazolidinediones / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone