Table 1

 Summary of findings in relevant studies discussed

Study acronymPatient NoTreatment armsTreatment durationPrimary target criterionOutcomeCV events
VIGOR108076Rheumatoid arthritis (RA); rofecoxib 50 mg daily (twice the maximum RA doses) or naproxen 500 mg bidMedian follow up of 9.0 monthsConfirmed clinical upper GI events (gastroduodenal perforation or obstruction, upper GI bleeding, and symptomatic gastroduodenal ulcers)2.1 confirmed GI events per 100 patient-years occurred with rofecoxib, as compared with 4.5 per 100 patient-years with naproxen (RR = 0.5; 95% CI 0.3 to 0.6; p<0.001)Incidence of MI was lower among patients in the naproxen group than among those in the rofecoxib group (0.1% v 0.4%; RR = 0.2; 95% CI 0.1 to 0.7); the overall mortality rate and the rate of death from CV causes were similar in the two groups
CLASS138059Osteoarthritis (OA); RA; celecoxib 400 mg bid (2 and 4 times the maximum RA and OA doses, respectively); ibuprofen 800 mg tid; or diclofenac 75 mg bid. Aspirin use for CV prophylaxis (325 mg/day) was permitted57% received treatment for 6 monthsIncidence of prospectively defined symptomatic upper GI ulcers and ulcer complications (bleeding, perforation, and obstruction)For patients not taking aspirin, the annualised incidence rates of upper GI ulcer complications alone and combined with symptomatic ulcers for celecoxib v NSAIDs were 0.44% v 1.27% (p = 0.04) and 1.40% v 2.91% (p = 0.02)No difference was noted in the incidence of CV events between celecoxib and NSAIDs, irrespective of aspirin use
TARGET26,2518325OA; lumiracoxib 400 mg once a day, naproxen 500 mg bid, or ibuprofen 800 mg tid in two substudies of identical design. Randomisation was stratified for low dose aspirin use and age1 YearDifference in time-to-event distribution of upper GI ulcer complications (bleeding, perforation, or obstruction)26 Antiplatelet Trialists’ Collaboration end point of non-fatal and silent MI, stroke, or CV death25In patients not taking aspirin, the cumulative 1 year incidence of ulcer complications was 1.09% (95% CI 0.82 to 1.36) with NSAIDs (64 events) v 0.25% (95% CI 0.12 to 0.39) with lumiracoxib (14 events; HR =  0.21 (95% CI 0.12 to 0.37), p<0.0001)Incidence of the primary end point was low, both with lumiracoxib (59 events (0.65%)) and the NSAIDs (50 events (0.55%); HR = 1.14 (95% CI 0.78 to 1.66), p = 0.5074)
APPROVe12,442586Rofecoxib 25 mg bid, and placebo36 MonthsColorectal adenoma chemoprevention in subjects with an increased riskReduced rate of adenoma recurrence, years 0–3 RR = 0.75 (95% CI 0.67 to 0.83), p<0.001,1.50 confirmed thrombotic events per 100 patient-years in the rofecoxib group, as compared with 0.78 events per 100 patient-years in the placebo group. Corresponding RR = 1.92 (95% CI 1.19 to 3.11; p = 0.008)
APC 14–162035Comparing two doses of celecoxib (200 mg or 400 mg bid) with placebo2.8–3.1 YearsColorectal adenoma chemopreventionNot reportedPotentially serious CV events were reached in 1% in the placebo group, as compared with 2.3% in the celecoxib 200 mg twice daily group (HR = 2.3; 95% CI 0.9 to 5.5) and with 3.4% in the 400 mg celecoxib twice daily group (HR = 3.4; 95% CI 1.4 to 7.8)
PreSAP15,161561A similar study to APC comparing celecoxib 400 mg once a day versus placeboAbout 33 monthsTo prevent colon polypsNot reportedPatients taking celecoxib 400 mg once a day versus placebo did not have increased CV risk
Aspirin to Prevent Colorectal Adenomas371121Placebo, 81 mg of aspirin, or 325 mg of aspirin dailyAbout 3 yearsChemoprevention against colorectal adenomas in subjects with an increased riskUnadjusted relative risks of any adenoma (as compared with the placebo group) were 0.81 in the 81 mg aspirin group (95% CI 0.69 to 0.96) and 0.96 in the 325 mg group (95% CI 0.81 to 1.13)Non-fatal MI and stroke, respectively, occurred somewhat more frequently in the aspirin groups than in the placebo group. The calculated RR of combined CV end point was 10 (95% CI 1.3 to 78; p = 0.006)
ADAPT17About 2400 volunteer participantsNaproxen 220 mg bid and celecoxib 200 mg bid or placeboUp to 3 yearsDecreasing the risk of developing Alzheimer’s disease in people ⩾70 years of ageNot reportedNo significant increase in CV and cerebrovascular risk for celecoxib; increase in events among the participants taking naproxen in comparison with those receiving placebo
CABG-118462Intravenous parecoxib 40 mg given within 30 minutes after extubation and every 12 hours for a minimum of 3 days followed by oral valdecoxib 40 mg every 12 hours for a combined total of 14 days14 DaysAnalgesic efficacy of the study drug in patients undergoing coronary artery bypass grafting surgery through a median sternotomyStudy drug was significantly better than control treatmentMyocardial infarction was reported in 1.6% (5/311) of P/V group patients versus 0.7% (1/151) of control patients (p = 0.669). Cerebrovascular complications occurred in 9 (2.9%) P/V group patients versus 1 (0.7%) patient in the control group (p = 0.177)
CABG-2191671Intravenous parecoxib 40 mg for at least 3 days, followed by oral valdecoxib 20 mg every 12 hours through day 10; intravenous placebo followed by oral valdecoxib 20 mg every 12 hours; or placebo for 10 days10 DaysFrequency of predefined adverse events, including CV events, renal failure or dysfunction, gastroduodenal ulceration, and wound healing complicationsAs compared with placebo alone, both parecoxib and valdecoxib and placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse eventCardiovascular events (including MI, cardiac arrest, stroke, and pulmonary embolism) were more common among the patients given parecoxib and valdecoxib than among those given placebo (2.0% v 0.5%; RR = 3.7; 95% CI 1.0 to 13.5; p = 0.03)
General Surgery Safety Study 211050Initial dose of parecoxib 40 mg IV, then 20 mg IV Q12H for a minimum of 3 days followed by oral valdecoxib (20 mg Q12H) (n = 525) for the remainder of a 10 day treatment period, or placebo IV followed by oral placebo (n = 525)10 DaysAnalgesic efficacy of the study drug in patients undergoing orthopaedic/general surgeryNot reportedNo significant differences in the overall safety profile