Summary of findings in relevant studies discussed
| Study acronym | Patient No | Treatment arms | Treatment duration | Primary target criterion | Outcome | CV events |
|---|---|---|---|---|---|---|
| VIGOR10 | 8076 | Rheumatoid arthritis (RA); rofecoxib 50 mg daily (twice the maximum RA doses) or naproxen 500 mg bid | Median follow up of 9.0 months | Confirmed 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 |
| CLASS13 | 8059 | Osteoarthritis (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 permitted | 57% received treatment for 6 months | Incidence 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 |
| TARGET26,25 | 18325 | OA; 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 age | 1 Year | Difference 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 death25 | In 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) |
| APPROVe12,44 | 2586 | Rofecoxib 25 mg bid, and placebo | 36 Months | Colorectal adenoma chemoprevention in subjects with an increased risk | Reduced 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 14–16 | 2035 | Comparing two doses of celecoxib (200 mg or 400 mg bid) with placebo | 2.8–3.1 Years | Colorectal adenoma chemoprevention | Not reported | Potentially 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) |
| PreSAP15,16 | 1561 | A similar study to APC comparing celecoxib 400 mg once a day versus placebo | About 33 months | To prevent colon polyps | Not reported | Patients taking celecoxib 400 mg once a day versus placebo did not have increased CV risk |
| Aspirin to Prevent Colorectal Adenomas37 | 1121 | Placebo, 81 mg of aspirin, or 325 mg of aspirin daily | About 3 years | Chemoprevention against colorectal adenomas in subjects with an increased risk | Unadjusted 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) |
| ADAPT17 | About 2400 volunteer participants | Naproxen 220 mg bid and celecoxib 200 mg bid or placebo | Up to 3 years | Decreasing the risk of developing Alzheimer’s disease in people ⩾70 years of age | Not reported | No significant increase in CV and cerebrovascular risk for celecoxib; increase in events among the participants taking naproxen in comparison with those receiving placebo |
| CABG-118 | 462 | Intravenous 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 days | 14 Days | Analgesic efficacy of the study drug in patients undergoing coronary artery bypass grafting surgery through a median sternotomy | Study drug was significantly better than control treatment | Myocardial 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-219 | 1671 | Intravenous 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 days | 10 Days | Frequency of predefined adverse events, including CV events, renal failure or dysfunction, gastroduodenal ulceration, and wound healing complications | As compared with placebo alone, both parecoxib and valdecoxib and placebo and valdecoxib had a higher proportion of patients with at least one confirmed adverse event | Cardiovascular 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 21 | 1050 | Initial 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 Days | Analgesic efficacy of the study drug in patients undergoing orthopaedic/general surgery | Not reported | No significant differences in the overall safety profile |