BACKGROUND: The timing of cardiovascular risks associated with the use of cyclooxygenase-2 (COX-2) inhibitors is unclear. Using data collected in a previous population-based cohort study of elderly people starting nonsteroidal anti-inflammatory drug (NSAID) therapy, we evaluated the temporal nature of the risk of a first myocardial infarction (MI) associated with the use of rofecoxib and celecoxib. METHODS: We identified people 66 years of age or older without previous MI who were currently taking rofecoxib and celecoxib using Quebec's computerized health databases (January 1999 to June 2002). Data on use and MI outcome were analyzed using a time-matched, nested case-control approach with rate ratios, comparing current users and non-users of rofecoxib and celecoxib in the year preceding the index date, estimated using conditional logistic regression. RESULTS: The risk of MI was highest following first-time use of rofecoxib (adjusted rate ratio [RR] 1.67, 95% confidence interval [CI] 1.21-2.30), with events occurring within a median of 9 (6-13) days after therapy was started. The risk increase for first-time use of celecoxib was not statistically significant (RR 1.29, 95% CI 0.90-1.83). Repeated exposure to rofecoxib was associated with a small but statistically nonsignificant delayed risk (RR 1.17, 95% CI 0.98-1.40), but no risk was seen with celecoxib (RR 0.97, 95% CI 0.82-1.14). Treatment duration was not associated with increasing risk for either agent. The risk remained elevated for the first 7 days after rofecoxib was discontinued (RR 1.23, 95% CI 1.05-1.44) but appeared to return to baseline between day 8 and 30 (RR 0.82, 95% CI 0.61-1.09). INTERPRETATION: A small proportion of patients using rofecoxib for the first time had their first MI shortly after starting the drug. This risk did not increase with the length of treatment and returned to baseline shortly after treatment was discontinued. More research is needed to identify those most susceptible to cardiotoxicity mediated by COX-2 inhibitor therapy.
BACKGROUND: The timing of cardiovascular risks associated with the use of cyclooxygenase-2 (COX-2) inhibitors is unclear. Using data collected in a previous population-based cohort study of elderly people starting nonsteroidal anti-inflammatory drug (NSAID) therapy, we evaluated the temporal nature of the risk of a first myocardial infarction (MI) associated with the use of rofecoxib and celecoxib. METHODS: We identified people 66 years of age or older without previous MI who were currently taking rofecoxib and celecoxib using Quebec's computerized health databases (January 1999 to June 2002). Data on use and MI outcome were analyzed using a time-matched, nested case-control approach with rate ratios, comparing current users and non-users of rofecoxib and celecoxib in the year preceding the index date, estimated using conditional logistic regression. RESULTS: The risk of MI was highest following first-time use of rofecoxib (adjusted rate ratio [RR] 1.67, 95% confidence interval [CI] 1.21-2.30), with events occurring within a median of 9 (6-13) days after therapy was started. The risk increase for first-time use of celecoxib was not statistically significant (RR 1.29, 95% CI 0.90-1.83). Repeated exposure to rofecoxib was associated with a small but statistically nonsignificant delayed risk (RR 1.17, 95% CI 0.98-1.40), but no risk was seen with celecoxib (RR 0.97, 95% CI 0.82-1.14). Treatment duration was not associated with increasing risk for either agent. The risk remained elevated for the first 7 days after rofecoxib was discontinued (RR 1.23, 95% CI 1.05-1.44) but appeared to return to baseline between day 8 and 30 (RR 0.82, 95% CI 0.61-1.09). INTERPRETATION: A small proportion of patients using rofecoxib for the first time had their first MI shortly after starting the drug. This risk did not increase with the length of treatment and returned to baseline shortly after treatment was discontinued. More research is needed to identify those most susceptible to cardiotoxicity mediated by COX-2 inhibitor therapy.
Authors: Muhammad Mamdani; Paula Rochon; David N Juurlink; Geoffrey M Anderson; Alex Kopp; Gary Naglie; Peter C Austin; Andreas Laupacis Journal: Arch Intern Med Date: 2003-02-24
Authors: C Bombardier; L Laine; A Reicin; D Shapiro; R Burgos-Vargas; B Davis; R Day; M B Ferraz; C J Hawkey; M C Hochberg; T K Kvien; T J Schnitzer Journal: N Engl J Med Date: 2000-11-23 Impact factor: 91.245
Authors: Elisabeth Ott; Nancy A Nussmeier; Peter C Duke; Robert O Feneck; R Peter Alston; Michael C Snabes; Richard C Hubbard; Ping H Hsu; Lawrence J Saidman; Dennis T Mangano Journal: J Thorac Cardiovasc Surg Date: 2003-06 Impact factor: 5.209
Authors: Daniel H Solomon; Sebastian Schneeweiss; Robert J Glynn; Yuka Kiyota; Raisa Levin; Helen Mogun; Jerry Avorn Journal: Circulation Date: 2004-04-19 Impact factor: 29.690
Authors: Yuka Kiyota; Sebastian Schneeweiss; Robert J Glynn; Carolyn C Cannuscio; Jerry Avorn; Daniel H Solomon Journal: Am Heart J Date: 2004-07 Impact factor: 4.749
Authors: Victor Prima; Lyudmila N Kaliberova; Sergey Kaliberov; David T Curiel; Sergei Kusmartsev Journal: Proc Natl Acad Sci U S A Date: 2017-01-17 Impact factor: 11.205
Authors: Benedict W Wheeler; Chris Metcalfe; David Gunnell; Peter Stephens; Richard M Martin Journal: Br J Clin Pharmacol Date: 2009-11 Impact factor: 4.335
Authors: Julia Metzner; Laura Popp; Claudiu Marian; Ronald Schmidt; Christine Manderscheid; Christoph Renne; Beate Fisslthaler; Ingrid Fleming; Rudi Busse; Gerd Geisslinger; Ellen Niederberger Journal: J Mol Med (Berl) Date: 2007-02-22 Impact factor: 5.606