Myocardial infarction coxib

The development of these drugs allowed the circumvention of the negative gastrointestinal effects while effectively reducing inflammation. However, it was subsequently shown that both NSAIDs and Coxibs can raise the risk of myocardial infarction, when taken on a chronic basis for at least 18 months. In 2004 rofecoxib was taken off the market for this reason. 

The selectivity of coxibs for COX-2 over COX-1 gives them antiinflammatory and antiproliferative actions with rednced G1 side effects, bnt it also makes them ineffective as antiplatelet agents and thns increases risks from myocardial infarction and stroke. 

Initially this increased risk of myocardial infarction was attributed to the myocardial protective properties of the nonselective COX inhibitors. COX-2 selective inhibitors may lack this protective capability. Later meta analysis suggested that the degree of myoprotection associated with naproxen could not account for the difference in the incidence of myocardial infarction. Merck, the maker of rofecoxib, withdrew the drug from the market because of this association. The other two coxibs, celecoxib and lumiracoxib, remain on the market as no similar increase in myocardial infarction has been associated with these drugs. It must be stated here that there is controversy regarding this issue and only time will provide the ultimate answer regarding the car-diotoxic potential of these two coxibs. 

In a double-blind, placebo-controlled study in 72 patients undergoing laparoscopic cholecystectomy, oral etoricoxib 120 mg given 1.5 hours before surgery reduced the need for postoperative patient controlled analgesia (PCA) with fentanyl, but opioid-related adverse effects were not reduced. Furthermore, the safety of short-term perioperative use of coxibs has been questioned, as some studies have reported more adverse effects (including myocardial infarction, cardiac arrest, stroke, and pulmonary embolism) with parecoxib or valdecoxib compared with placebo. ... 

Several studies have suggested that regular use of coxibs increases the risk of myocardial infarction. New analyses have confirmed this view. In a retrospective cohort study (n = 38 258 patients 26 376 patient-years), the odds of acute myocardial infarction during exposure to etodolac, naproxen, celecoxib, or rofecoxib were reported. Compared with naproxen, there was no significantly increased risk with etodolac, whereas with celecoxib (OR = 2.18 95% Cl = 1.09, 4.35) and rofecoxib (OR = 2.16 95% Cl = 1.04, 4.46) there was an increased risk [8 ]. 

In a case-control study using drug-dispensing and hospitalization data from more than 2 million residents in The Netherlands, subjects with a first hospitalization for acute myocardial infarction, cardiovascular and gastrointestinal events were identified [14 J. Use of coxibs and non-selective NSAIDs was classified into remote, recent, and current use. Compared with remote use, the risk of acute myocardial infarction was increased in current users of all coxibs (adjusted OR = 1.73 95% Cl = 1.37, 2.19) and all non-selective NSAIDs (adjusted OR = 1.41 95% Cl = 1.23, 1.61). Analysis by separate agents showed that the risk of acute myocardial infarction was increased with celecoxib (OR = 2.53 95% Cl = 1.53, 4.18), rofecoxib (OR = 1.60 95% Cl = 1.22, 2.10), ibuprofen (OR = 1.56 95% Cl — 1.19, 2.05), and diclofenac (OR = 1.51 95% Cl = 1.22, 1.87), but not with naproxen (OR = 1.21 95% Cl = 0.87,1.68). 

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