Exogenous estrogen does not attenuate the association between rofecoxib and myocardial infarction in perimenopausal women

Abstract

Rofecoxib has been proposed to increase the risk of myocardial infarction (MI) through suppression of cyclooxygenase 2–mediated prostacyclin. Estrogen may have protective effects through augmenting cyclooxygenase 2 expression and subsequently increasing prostacyclin. Estrogen may attenuate the association between rofecoxib and MI. We used 1999–2002 Medicaid claims data to measure the MI hazard ratio (HR) attributed to rofecoxib exposure in estrogen-exposed and unexposed 45- to 65-year-old women.We identified 184,169 female rofecoxib users who contributed 309,504 person-years and experienced 1217 first MIs. Estrogen exposure seemed protective [MI-HR 0.72; 95% confidence interval (CI), 0.62–0.84] in this cohort. Rofecoxib was associated with an elevated MI-HR in both estrogen-exposed (2.01; 95% CI, 1.60–2.54) and estrogen-unexposed women (1.69; 95% CI, 1.43–1.99). The rofecoxib–estrogen interaction ratio was not significantly different from 1 (1.19; 95% CI, 0.91–1.57). Although estrogen use was associated with a lower risk of MI, it did not seem to attenuate the association between rofecoxib and MI.

Figure 1

Study design includes a 90 day covariate selection window during which Medicaid eligibility is confirmed and baseline covariate information was collected. Cohort observation time began with each woman’s rofecoxib unexposed time prior to first rofecoxib prescription. Their rofecoxib exposure time began with their first rofecoxib prescription and ended with last continuous rofecoxib prescription. Women who had an estrogen prescription at any time during the cohort observation time were considered estrogen exposed.