The Tell-Tale Heart: Population-Based Surveillance Reveals an Association of Rofecoxib and Celecoxib with Myocardial Infarction

Abstract

BackgroundCOX-2 selective inhibitors are associated with myocardial infarction (MI). We sought to determine whether population health monitoring would have revealed the effect of COX-2 inhibitors on population-level patterns of MI.Methodology/Principal FindingsWe conducted a retrospective study of inpatients at two Boston hospitals, from January 1997 to March 2006. There was a population-level rise in the rate of MI that reached 52.0 MI-related hospitalizations per 100,000 (a two standard deviation exceedence) in January of 2000, eight months after the introduction of rofecoxib and one year after celecoxib. The exceedence vanished within one month of the withdrawal of rofecoxib. Trends in inpatient stay due to MI were tightly coupled to the rise and fall of prescriptions of COX-2 inhibitors, with an 18.5% increase in inpatient stays for MI when both rofecoxib and celecoxib were on the market (P<0.001). For every million prescriptions of rofecoxib and celecoxib, there was a 0.5% increase in MI (95%CI 0.1 to 0.9) explaining 50.3% of the deviance in yearly variation of MI-related hospitalizations. There was a negative association between mean age at MI and volume of prescriptions for celecoxib and rofecoxib (Spearman correlation, −0.67, P<0.05).Conclusions/SignificanceThe strong relationship between prescribing and outcome time series supports a population-level impact of COX-2 inhibitors on MI incidence. Further, mean age at MI appears to have been lowered by use of these medications. Use of a population monitoring approach as an adjunct to pharmacovigilence methods might have helped confirm the suspected association, providing earlier support for the market withdrawal of rofecoxib.

Potential for Electronic Health Records and Online Social Networking to Redefine Medical Research

“…One study of such an automated system monitored 36 653 inpatients over an 18-month period and correctly identified 731 ADEs in patients, whereas health professionals only reported 92 (18 ). A study published by one of the authors showed the potential for automated signal detection through population monitoring to detect early signs of COX-2 inhibitor's association with myocardial infarction (21 ). Although there are potential difficulties in translating data entry from physician-based EHRs to accurately detect signals, one study found consistency between natural language processing characterization of patients with asthma with known population characteristics (22 ), providing further validation of this approach.…”

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“…Other industries, such as finance and energy, have embraced data analytics [6], and researchers at Google have shown that an order of magnitude growth in the size of data sets leads to significant improvements in performance of analyses and can overshadow improvements in modeling techniques [7]. Big data have only been reported in a select few epidemiologic studies, such as those linking myocardial infarction and rosiglitazone [8] or rofecoxib [9]. Two significant issues need to be resolved to enable open data mandates: guaranteeing the privacy of study subjects [10] and creating a safe, fair, and open infrastructure for data sharing [4].…”