Rofecoxib, valdecoxib associated with increased risk of stroke

Key Points

A retrospective cohort study published in the journal Stroke demonstrated an increased risk of stroke among users of rofecoxib and valdecoxib but not among users of other nonsteroidal anti-inflammatory drugs (NSAIDs).

In 2004, rofecoxib was withdrawn from the market because of an increased risk of serious cardiovascular adverse events; valdecoxib was withdrawn from the market less than a year later for similar reasons. In the current study, the investigators focused on the potential risk of cerebrovascular events in patients treated with rofecoxib, valdecoxib, or other NSAIDs, including celecoxib, ibuprofen, and naproxen.

This study evaluated noninstitutionalized patients aged 50 to 84 years who were enrolled in the Tennessee Medicaid program between 1999 and 2004. Patients were excluded if they had evidence of a prior stroke or other serious medical illness in the year before entry. Patients included in the study (N=336,906; 989,826 person-y of follow-up) were followed until development of stroke, a serious medical illness, disenrollment, death, or study end. The use or nonuse of celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, indomethacin, diclofenac, or other NSAIDs was assessed for each study patient; the reference group was composed of nonusers. The study outcome was the occurrence of hospitalization with a primary discharge diagnosis indicating fatal or nonfatal ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage.

In another analysis, investigators assessed stroke hospitalizations among new users of NSAIDs (patients with no NSAID use in the previous 365 days). New users of rofecoxib demonstrated 6.06 stroke hospitalizations per 1,000 person-years (adjusted HR=1.46; 95% CI, 1.08–1.98), and new users of valdecoxib demonstrated 6.19 stroke hospitalizations per 1,000 person-years (adjusted HR=1.39; 95% CI, 0.74–2.59). New users of other NSAIDs did not demonstrate a significantly increased risk of stroke hospitalization.

The investigators stated that although their data "provide some reassurance about the NSAIDs that remain on the market," healthcare professionals should exercise caution when using these drugs in patients at high risk for cardiovascular and cerebrovascular events.

Source

Roumie CL, Mitchel EF Jr, Kaltenbach L, Arbogast PG, Gideon P, Griffin MR. Nonaspirin NSAIDs, cyclooxygenase 2 inhibitors, and the risk for stroke. Stroke. 2008;39:2037–2045.