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A short course of adjunctive celecoxib after implantation of a drug-eluting stent (DES) reduces late loss, but any clinical benefit appears to be undercut by increased thrombotic events, according to a study published online March 8, 2012, ahead of print in the European Heart Journal.

Researchers led by Hyo-Soo Kim, MD, PhD, of Seoul National University Hospital (Seoul, South Korea), randomized 909 patients undergoing PCI at 5 South Korean centers to 3 months of the COX-2 inhibitor celecoxib (n = 442; Celebrex, Pfizer, New York, NY; 200 mg twice daily) or to a control group (n = 454). In a separate analysis, patients were stratified by stent type into paclitaxel-eluting stent (PES; Taxus Liberté, Boston Scientific, Natick, MA) and zotarolimus-eluting stent (ZES; Endeavor, Medtronic CardioVascular, Santa Rosa, CA) subgroups.

Improved Late Loss Only Benefit

Six-month angiographic follow-up was available for 88% of patients. For the overall cohort, late luminal loss was reduced by 14% in the celecoxib group compared with the control group. However, in-stent minimal luminal diameter (MLD) and restenosis rates did not differ between the celecoxib group and controls (table 1).

Table 1. Angiographic Results at 6 Months

Celecoxib showed only a trend toward reduced late loss in both DES subgroups:

• PES: 0.49 ± 0.45 mm vs. 0.56 ± 0.50 mm; P = 0.12
• ZES: 0.65 ± 0.50 mm vs. 0.76 ± 0.58 mm; P = 0.07

At a mean follow-up of 6.8 months, Kaplan-Meier estimates showed no difference in rates of MACE (cardiac death, MI, TLR) or TLR but did show a trend toward reduced clinically driven TLR. However, rates of MI and cardiac death were higher in the celecoxib group (table 2).

Table 2. Clinical Outcomes at 6 Months

Specifically, in the celecoxib group there were 4 cases of MI due to stent thrombosis (1 fatal) and 2 sudden cardiac deaths, while in the control group there was only 1 nonfatal MI due to stent thrombosis.

In addition, there was no interaction between the treatment effect of celecoxib on cardiac events and key clinical and angiographic variables including sex, age, diabetes, LAD location, type C lesion, DES type, or use of cilostazol.

Six percent of celecoxib patients discontinued the drug before the recommended 3 months. The most common reason was patient preference (n = 15), although some experienced GI discomfort (n = 6), skin rash or pruritus (n = 6), or headache (n = 1). Two patients suffered an adverse event several months after discontinuation of the drug—one died and the other underwent TLR.

Noting that the extent of late loss reduction associated with celecoxib was more modest in the current trial compared with the earlier COREA-TAXUS trial (14% vs. 34%), the authors say the smaller difference is largely due to a lower late loss in the Mini-COREA control group. And that, in turn, can be explained by multiple differences in the protocols of the 2 trials.

Dr. Kim and colleagues note that although experts generally discourage use of unopposed COX-2 inhibitors, meta-analyses have not shown that they increase cardiovascular risk. And the large, randomized PRECISION trial specifically comparing celecoxib with 2 other nonselective NSAIDs in high-risk patients is not expected to be completed until 2014.

Risk Outweighs Benefit

In a telephone interview with TCTMD, C. Michael Gibson, MD, of Beth Israel Deaconess Medical Center (Boston, MA), said it is important to consider the relative importance of the angiographic and clinical results. “In my mind, the increased risk of death and MI outweighs the small improvement in late loss,” he observed. “In fact, diminishing late loss may actually promote the exposure of metal struts to the bloodstream and increase the risk of thrombosis.” 

In a similar vein, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview that the researchers’ effort to find a therapeutic window for celecoxib failed. Even the slight reduction in late loss did not translate into a restenosis benefit, he noted.

Moreover, Drs. Gibson and Brener both observed that with newer-generation stents, late loss has become less of an issue. “And here you are looking at 2 stents [Taxus Liberté and Endeavor] that have the highest rates of late loss that we know of—about 4 times greater than the newest stent,” Dr. Brener said. “So if [the angiographic advantage] was marginal in this group, you can imagine that when there is very low late loss to begin with, celecoxib would be even less likely to be of benefit.”

No PCI Future for Celecoxib?

There appears to be no future for use of celecoxib in PCI patients, Dr. Brener said. The biology behind the cardiovascular risk of COX-2 inhibitors is fairly well established, he asserted, stressing that “unless the PRECISION trial teaches us something different,” patients with coronary disease should not use celecoxib.

In fact, that is what the guidelines recommend, Dr. Brener added, although they do sanction use of a short course of COX-2 inhibitors at a low dose in non-ACS patients with severe arthritis. According to Dr. Gibson, such patients “should be advised of the very small but real risk of a heart attack.” Then they must decide whether any symptomatic relief that may be provided is worth the risk.

However, both physicians said they would never mention diminished late loss to such patients facing elective PCI as something to be factored into decision making. “Just because you make the angiogram look better doesn’t mean it helps the patient,” Dr. Gibson commented.

 

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Source:
Kang H-J, Oh I-Y, Chung J-W, et al. 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;Epub ahead of print.

 

 

Related Stories:

• Celecoxib’s Post-PCI Efficacy Maintained Long-Term with No Safety Signal
• Meta-Analysis: Adjunctive Cilostazol Lowers Repeat Revascularization After PCI

 

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