A previous trial (2) demonstrated that 6-month adjunctive use of celecoxib reduced target-lesion revascularization (TLR) without increased thrombotic risk. In a larger prospective, randomized trial, Kang et al. aimed to confirm the effects of 3-month celecoxib in patients receiving drug-eluting stent (DES) implantation.909 patients treated for native coronary lesions were randomized to the control and the celecoxib group with stratification into paclitaxel-eluting stent (PES) or zotarolimus-eluting stent (ZES) groups. In the celecoxib group, 200 mg of celecoxib was given twice daily for 3 months after the procedure. The primary endpoint was in-stent late loss (LL) at 6 months. In-stent LL was significantly lower in the celecoxib group than the control group (0.64 ± 0.54 vs. 0.55 ± 0.47 mm, P = 0.02). The trend of LL reduction in the celecoxib group was maintained in the ZES and PES subgroups, although it did not reach statistical significance. There was a trend towards the reduced clinically driven TLR in the celecoxib group (5.7 vs. 3.2%, log-rank P = 0.09), but adverse cardiac events rate did not differ between the two groups (composite of cardiac death, non-fatal myocardial infarction, and TLR; 8.6 vs. 7.7%, log-rank P = 0.84). However, non-fatal myocardial infarction and cardiac death occurred in 1.6% of the patients in the celecoxib group when compared with 0.2% in the control group (log-rank P = 0.03).
The authors conclude that three-month adjunctive celecoxib appears to reduce LL of DES, but state that the data may raise the concern about increased thrombotic risk with celecoxib even in patients receiving dual anti-platelet therapy.
The results are interesting in the context of the prior controversy about the risk of cardiovascular events with COX-2 inhibitors (3, 4, 5). A large randomized-controlled trial (PRECISION) is currently being performed to evaluate the cardiovascular safety of celecoxib in comparison with the two other commonly used non-selective NSAIDs in patients who are at high cardiovascular risk.(6)
1. Kang HJ, Oh IY, Chung JW, Yang HM, Suh JW, Park KW, Kwon TK, Lee HY, Cho YS, Youn TJ, Koo BK, Kang WY, Kim W, Rha SW, Bae JH, Chae IH, Choi DJ, Kim HS. Effects of Celecoxib On Restenosis after Coronary Intervention and Evolution of Atherosclerosis (Mini-COREA) Trial: celecoxib, a double-edged sword for patients with angina. Eur Heart J. 2012 Mar 8. [Epub ahead of print] PMID: 22408034
2. Koo BK, Kim YS, Park KW, Yang HM, Kwon DA, Chung JW, Hahn JY, Lee HY, Park JS, Kang HJ, Cho YS, Youn TJ, Chung WY, Chae IH, Choi DJ, Oh BH, Park YB, Kim HS. Effect of celecoxib on restenosis after coronary angioplasty with a Taxus stent (COREA-TAXUS trial): an open-label randomised controlled study. Lancet. 2007 Aug 18;370(9587):567-74. Erratum in: Lancet. 2007 Sep 14;370(9590):828. PMID: 17707751
3. Mukherjee D, Nissen SE, Topol EJ. Risk of cardiovascular events associated with selective COX-2 inhibitors. JAMA. 2001 Aug 22-29;286(8):954-9. PMID: 11509060
4. McGettigan P, Henry D. Cardiovascular risk and inhibition of cyclooxygenase: a systematic review of the observational studies of selective and nonselective inhibitors of cyclooxygenase 2. J Am Med Assoc 2006;296:1633-1644.
5. Graham DJ, Campen D, Hui R, Spence M, Cheetham C, Levy G, Shoor S, Ray WA. Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case–control study. Lancet 2005;365:475-481.
6. Becker MC, Wang TH, Wisniewski L, Wolski K, Libby P, Luscher TF, Borer JS, Mascette AM, Husni ME, Solomon DH, Graham DY, Yeomans ND, Krum H, Ruschitzka F, Lincoff AM, Nissen SE. Rationale, design, and governance of Prospective Randomized Evaluation of Celecoxib Integrated Safety versus Ibuprofen Or Naproxen (PRECISION), a cardiovascular end point trial of nonsteroidal antiinflammatory agents in patients with arthritis. Am Heart J 2009;157:606-612. [ClinicalTrials.gov Identifier: NCT00346216]