A new "Comparative Effectiveness" assessment strategy using the THIN database: comparison of the cardiac complications of pioglitazone and rosiglitazone.
OBJECTIVE
Examine feasibility of a new strategy to perform Electronic Medical Record database valid Comparative Effectiveness Research (CER), using determination of whether rosiglitazone (ROS) treatment increases Acute myocardial infarction (MI) in comparison to pioglitazone (PIO) as a model question.


METHODS
Using the UK The Health Improvement Network Database, a retrospective cohort design replicated the proactive RCT of diabetics with ischemic cardiovascular disease (CVD). Replication studies using PIO or ROS, as well as expanded studies of subjects not requiring CVD, were performed. MI assessment used multiple analytics comparing ROS and PIO exposed patients including: unexposed subjects, the proactive RCT, and directly between ROS to PIO exposed cohorts.


RESULTS
PIO replication studies did not affect MI [HR 0.88 (0.49 to 1.42)], but ROS increased MI, with prior event rate ratio (PERR) adjusted HR (which overcomes unmeasured confounding) results of: [HR 1.31 (0.94 to 1.74)] versus proactive RCT [HR 0.83 (0.65 to 1.06)] (p = 0.02). Direct ROS to PIO exposed cohort comparisons yielded PERR adj HR of 1.55 (0.98 to 2.65). By contrast, expanded studies showed no differences between ROS and PIO exposure.


CONCLUSIONS
These results provide new insight regarding the effects of ROS and PIO on MI. In a population with established ischemic CVD, ROS increased MI in contrast to PIO; whereas in an unselected population, ROS and PIO have reasonably comparable effects. Most importantly, this study demonstrates the feasibility and advantages of a new strategy to perform reliable "CER" using an EMR database.
University of Pennsylvania School of Medicine, Medicine, Philadelphia, Pennsylvania, USA. tannen@mail.med.upenn.edu
Richard
R
Tannen
Dawei
D
Xie
Xingmei
X
Wang
Menggang
M
Yu
Mark G
MG
Weiner
D000328:Adult; D000368:Aged; D015331:Cohort Studies; D057186:Comparative Effectiveness Research / Q000379:methods*; D016208:Databases, Factual; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy; D057286:Electronic Health Records; D005240:Feasibility Studies; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000139:chemically induced* / Q000453:epidemiology; D000077205:Pioglitazone; D016032:Randomized Controlled Trials as Topic; D012189:Retrospective Studies; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000009:adverse effects* / Q000627:therapeutic use
D007004:Hypoglycemic Agents; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone