A new retrospective cohort study published in PLOS One looks at the comparative safety of various nonsteroidal anti-inflammatory drugs (NSAIDs) when given concomitantly to patients taking clopidogrel.

Using Medicaid claims from 5 states (1999–2010) and Medicare claims for dual-enrollees, study authors analyzed the first concomitant use of clopidogrel and 1 of 10 selected NSAIDs (ibuprofen, celecoxib, naproxen, rofecoxib, meloxicam, diclofenac, indomethacin, valdecoxib, nabumetone, etodolac) after a 1-year baseline period. They evaluated incidences of all-cause mortality, acute myocardial infarction (AMI)/ischemic stroke, and gastrointestinal bleeding (GIB)/intracranial hemorrhage (ICH). The hazard ratio of each NSAID was calculated for each outcome. Ibuprofen served as the reference drug as it was the most commonly used NSAID in the cohort.

A total of 1,060,412 clopidogrel users were identified with 268,114 having overlapping NSAID prescriptions (48,483 person-years). There were 2,463 deaths (unadjusted incidence rate 50.8 per 1,000 person-years), 2,822 AMI/ischemic stroke outcomes (58.6 per 1,000 person-years), and 2,620 GIB/ICH outcomes (54.3 per 1,000 person-years).

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Compared with ibuprofen, rofecoxib was associated with a higher risk of mortality (hazard ratio [HR] 1.22, 95% CI: 1.04, 1.43) whereas valdecoxib was associated with a lower risk of mortality (HR 0.66, 95% CI: 0.48, 0.92). Indomethacin was associated with a higher risk of AMI/ischemic stroke (HR 1.38, 95% CI: 1.09, 1.74) and GIB/ICH (HR 2.18, 95% CI: 1.74, 2.73). Diclofenac (HR 1.65, 95% CI: 1.39, 1.97), naproxen (HR 1.47, 95% CI: 1.28, 1.70), and rofecoxib (HR 1.26, 95% CI: 1.08, 1.48) also demonstrated higher risks of GIB/ICH compared with valdecoxib (HR 0.73, 95% CI: 0.55, 0.98), which demonstrated a lower risk. 

The findings indicate that in patients taking concomitant clopidogrel, the differences in bleeding risk among these NSAIDs were more pronounced than the thrombotic risks. Lead author, Young Hee Nam, added, “Moreover, bleeding risk and thrombotic risk among individual NSAIDs did not appear to be inversely related to each other in the presence of clopidogrel.” The authors conclude that more research is needed to understand the biological mechanisms to assist in choosing the appropriate NSAID in clopidogrel users.

For more information visit plos.org.