Saturday, March 31, 2007
aspirin and NSAID's or coxibs
Summary and Comment
Effect of Aspirin on NSAID-Associated Ulcer Bleeding
Using low-dose aspirin concomitantly with coxibs negates coxibs’ benefit for lower bleeding risk.
Use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk for peptic ulcers and gastrointestinal bleeding. Selective cyclooxygenase-2 inhibitors (coxibs) confer lower risk for these complications. However, concomitant use of aspirin irreversibly and nonselectively inactivates the cyclooxygenase enzymes. Some data suggest that cotherapy with aspirin eliminates any benefit on bleeding risk that is imparted by coxibs.
To evaluate this issue, investigators performed a partially industry-supported case-control analysis. Cases were 2777 consecutive patients in the General Health System of Spain with endoscopy-proven upper gastrointestinal bleeding (UGIB) from peptic ulcers; 5532 age-matched patients without gastrointestinal disorders served as controls. All subjects were interviewed for medication use and medication history. Logistic regression analysis was used to determine odds ratios (ORs) for bleeding.
Current use of nonaspirin nonselective NSAIDs was associated with a fivefold increase in risk for bleeding (adjusted OR, 5.3; 95% CI, 4.5–6.2). Rofecoxib had a smaller effect (adjusted OR, 2.1; 95% CI, 1.1–4.0). Celecoxib and acetaminophen did not increase risk for bleeding; concomitant use of a proton-pump inhibitor (PPI) plus an NSAID also eliminated excess bleeding risk. Low-dose aspirin alone independently increased risk for bleeding, and also increased risk (with more than a simple additive effect) when combined with either nonselective NSAIDs or coxibs. The adjusted OR for nonselective NSAIDs went from 5.3 to 12.7 (95% CI, 7.0–23.0) with the addition of low-dose aspirin, and the adjusted OR for coxibs went from 1.0 to 14.5 (95% CI, 3.3–63.9). The authors concluded that prescribing coxibs instead of nonselective NSAIDs or prescribing PPIs as cotherapy with nonselective NSAIDs can lower risk for bleeding compared with nonselective NSAIDs alone, but the addition of low-dose aspirin negates these relative protective effects.
Comment: The mechanism of action responsible for aspirin’s antiplatelet effect —covalent alteration of the cyclooxygenase enzymes — logically would produce nonselective inactivation that would negate the selectivity of coxibs. This effect was seen early in trials of coxibs, when a relative reduction for bleeding was noted only among celecoxib patients who did not use low-dose aspirin (JAMA 2000; 284:1247). These results add further evidence that the benefits of the more-expensive coxibs disappear when used in conjunction with aspirin, even at low doses.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
Published in Journal Watch Gastroenterology March 30, 2007
Effect of Aspirin on NSAID-Associated Ulcer Bleeding
Using low-dose aspirin concomitantly with coxibs negates coxibs’ benefit for lower bleeding risk.
Use of nonselective nonsteroidal anti-inflammatory drugs (NSAIDs) increases risk for peptic ulcers and gastrointestinal bleeding. Selective cyclooxygenase-2 inhibitors (coxibs) confer lower risk for these complications. However, concomitant use of aspirin irreversibly and nonselectively inactivates the cyclooxygenase enzymes. Some data suggest that cotherapy with aspirin eliminates any benefit on bleeding risk that is imparted by coxibs.
To evaluate this issue, investigators performed a partially industry-supported case-control analysis. Cases were 2777 consecutive patients in the General Health System of Spain with endoscopy-proven upper gastrointestinal bleeding (UGIB) from peptic ulcers; 5532 age-matched patients without gastrointestinal disorders served as controls. All subjects were interviewed for medication use and medication history. Logistic regression analysis was used to determine odds ratios (ORs) for bleeding.
Current use of nonaspirin nonselective NSAIDs was associated with a fivefold increase in risk for bleeding (adjusted OR, 5.3; 95% CI, 4.5–6.2). Rofecoxib had a smaller effect (adjusted OR, 2.1; 95% CI, 1.1–4.0). Celecoxib and acetaminophen did not increase risk for bleeding; concomitant use of a proton-pump inhibitor (PPI) plus an NSAID also eliminated excess bleeding risk. Low-dose aspirin alone independently increased risk for bleeding, and also increased risk (with more than a simple additive effect) when combined with either nonselective NSAIDs or coxibs. The adjusted OR for nonselective NSAIDs went from 5.3 to 12.7 (95% CI, 7.0–23.0) with the addition of low-dose aspirin, and the adjusted OR for coxibs went from 1.0 to 14.5 (95% CI, 3.3–63.9). The authors concluded that prescribing coxibs instead of nonselective NSAIDs or prescribing PPIs as cotherapy with nonselective NSAIDs can lower risk for bleeding compared with nonselective NSAIDs alone, but the addition of low-dose aspirin negates these relative protective effects.
Comment: The mechanism of action responsible for aspirin’s antiplatelet effect —covalent alteration of the cyclooxygenase enzymes — logically would produce nonselective inactivation that would negate the selectivity of coxibs. This effect was seen early in trials of coxibs, when a relative reduction for bleeding was noted only among celecoxib patients who did not use low-dose aspirin (JAMA 2000; 284:1247). These results add further evidence that the benefits of the more-expensive coxibs disappear when used in conjunction with aspirin, even at low doses.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.)
Published in Journal Watch Gastroenterology March 30, 2007
# posted by roodbont @ 11:58 AM 
