2,528 patients with a family history of Alzheimer's Disease.
CVD/CBV death, MI, stroke, CHF, or TIA in the celecoxib-, naproxen-, and placebo-treated groups were 5.54%, 8.25%, and 5.68%, respectively. Death rates in the case of patients taking NSAIDs were higher but not statistically significant
74,838 users of NSAIDs and 23,535 users of other drugs.
The adjusted rate ratio for Rofecoxib was 1.16 for MI and 1.15 for stroke which was the highest among all other NSAIDs including other coxibs. Naproxen modestly reduced the rate ratio (RR for MI 0.067 and RR for stroke 0.083) of cardiovascular events
Multinational Etoricoxib and Diclofenac Arthritis Long-term (MEDAL) Study Program/Multinational
34,701 patients (24,913 with osteoarthritis and 9,787 with rheumatoid arthritis)
Thrombotic cardiovascular events occurred in 320 patients in the etoricoxib group and 323 patients in the diclofenac group with event rates of 1.24 and 1.30 per 100 patient-years and a hazard ratio of 0.95 for etoricoxib compared to diclofenac. Long term usage of either of these NSAIDs had similar effects on the rates of thrombotic cardiovascular events
19.3 months for etoricoxib and 19.1 months for diclofenac
4,086 patients with rheumatoid arthritis etoricoxib ; diclofenac
The rate of occurrence of AMI was higher in diclofenac (0.68) treated patients than in etoricoxib users (0.43). Also an overall increase in cardiac events was observed in diclofenac treated group (1.14) versus the etoricoxib group (0.83)
Ibuprofen, naproxen, diclofenac, meloxicam, indomethacin, piroxicam, and mefenamic acid
None/UK primary care
729,294 NSAID users; 443,047 controls
Increase in the relative rate for MI with cumulative and daily dose of ibuprofen and diclofenac. Higher risk of MI with diclofenac use (relative ratio = 1.21) than ibuprofen (relative ratio = 1.04) or naproxen (relative ratio = 1.03)
Celecoxib, rofecoxib, valdecoxib, ibuprofen, naproxen, diclofenac, and indomethacin
610,001 patients; without CVD ; with history of CVD
Rofecoxib (10.91 events/1000 person-years), valdecoxib (12.41 events/1000 person-years), and indomethacin (13.25 events/1000 person-years) increased CVD risk in patients with no history of CVD. Rofecoxib use increased risk of cardiovascular event in patients with CVD (30.28 events/1000 person-years)
Ibuprofen, diclofenac, naproxen, rofecoxib, celecoxib, valdecoxib, and etoricoxib
485,059 subjects with first hospitalisation for acute myocardial infarction, CV, and gastrointestinal events
AMI risk with celecoxib (OR 2.53), rofecoxib (OR 1.60), ibuprofen (OR 1.56), and diclofenac (OR 1.51) was significantly increased. Significant increase in CV risk with current use of individual COX-2 inhibitors and tNSAIDs (OR from 1.17 to 1.64). Significant decrease in AMI with current use of naproxen (OR 0.48)
INternational VErapamil Trandolapril STudy (INVEST)/Multinational
882 chronic NSAID users and 21,694 nonchronic NSAID users. Patients with hypertension and clinically stable coronary artery disease
Primary outcome like all-cause mortality, nonfatal MI, or nonfatal stroke and secondary individual outcomes like all-cause mortality, cardiovascular mortality, total MI, and total stroke occurred at a rate of 4.4 events per 100 patient-years in the chronic NSAID group, versus 3.7 events per 100 patient-years in the nonchronic NSAID group
MI: myocardial infarction, HF: heart failure, CVD: cardiovascular diseases, CBV: cerebrovascular diseases, CHF: congestive heart failure, HR: hazard ratio, OR: odd ratio, ND: not defined, RR: rate ratio, and TIA: transient ischemic attack. Various clinical trials suggest the increased incidences of CVD in NSAID users. The table lists only the clinical trials reported between 2006 and 2014.
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