SEOUL, South Korea -- The Cox-2 inhibitor celecoxib (Celebrex) used for six months after implantation of a paclitaxel-eluting stent reduced the risk of restenosis, researchers here found.
SEOUL, South Korea, Aug. 17 -- The Cox-2 inhibitor celecoxib (Celebrex) used for six months after implantation of a paclitaxel-eluting stent was safe and reduced the risk of restenosis, researchers here found.
In a randomized two-center trial with 274 patients, restenosis occurred in only 11% of patients given celecoxib compared with a 24% rate in untreated controls, Hyo-Soo Kim, M.D., Ph.D., of the Seoul National University Hospital, and colleagues, reported in the Aug. 18 issue of The Lancet.
Addressing recent concern about the risk of thrombosis for celecoxib, the researchers noted that it remains unclear whether celecoxib has the same effect as rofecoxib (Vioxx), recently withdrawn from the market.
They did note, however, that two meta-analyses have shown that celecoxib does not increase the risk of cardiovascular events.
The safety concern was also underscored by two editorialists in the same journal issue who wrote that the drug's safety for this use should be confirmed in studies assessing the risk of myocardial infarction and cardiac death.
The hypothesis that celecoxib, through its antiproliferative and anti-inflammatory effects, might decrease the rate of restenosis and the need for repeat procedures had not been tested, Dr. Kim and his colleagues said. Although, animal experiments had suggested that systemic treatment with celecoxib can reduce the formation of neointima within stents.
To test for similar effects in a clinical study, the researchers enrolled 274 patients with angina pectoris or a positive stress test. Patients had native coronary artery lesions for which implantation of paclitaxel-eluting stents was feasible.
All patients were given 100 mg of aspirin and 75 mg daily of clopidogrel (Plavix) a day. Celecoxib was added to the regimen of 136 randomly assigned patients -- 400 mg before the intervention, and 200 mg twice a day for six months after the procedure.
The mean in-stent late luminal loss was lower in the celecoxib group (0.49 mm, standard deviation 0.47) than in the control group (0.75 mm, 0.60; P<0.0001) for an absolute difference of 0.26 mm (95% CI 0.12-0.40).
The frequency of non-fatal myocardial infarction was also lower in the celecoxib group, mainly because of a reduced need for revascularization of the target lesion. Revascularization was 15% among the controls and 5% among the celecoxib patients, they reported.
The rate of adverse cardiac events within the first six moths was also lower in the celecoxib group than among the controls, again primarily because of a lower need for revascularization.
Periprocedural MI occurred in 15% of the control group and 14% in the celecoxib group (P=0.85).
During a month of follow-up, there was one sudden cardiac death in the control group and one non-fatal MI related to stent thrombosis in a celecoxib patient.
Discussing the study's limitations, the researchers listed its open-label, uncontrolled design; the fact the angiography results were analyzed in more than one lab; and because angiographic follow-up was at six months after the implantation, neointimal growth after this point was not assessed.
Because the follow-up of the study was short, the researchers wrote, they could not comment on the safety of using celecoxib for several years. But taking the drug for six months, did not seem to increase the risk of adverse cardiac events in the intermediate term when used with dual antiplatelet therapy.
"We will be interested to see the two-to five-year follow-up results of this cohort," they concluded.
In an accompanying comment, Francesco Pelliccia, M.D., and Vincenzo Pasceri, M.D., of Ospedale San Filippo Neri in Rome, called the results impressive. They noted, however, that the restenosis rate was high for a study with drug-eluting stents and should therefore not be extrapolated to other patient populations.
This strategy is appealing they wrote, but "several issues should be addressed before anti-inflammatory drugs are proposed for everyday use."
Although celecoxib might be beneficial even when given for a short time before and after coronary angioplasty, the safety of this drug in interventional cardiology should be confirmed by studies powered to assess the risk of myocardial infarction and cardiac death, Drs. Pelliccia and Pasceri said.
Gastrointestinal tolerability of chronic therapy with both celecoxib and dual antiplatelet therapy (aspirin and clopidogrel) might also be a drawback, they said.
Although the study demonstrated that systemic therapy might still have a role in prevention of restenosis even in the era of drug-eluting stents, they added that further studies are needed.
It is still necessary to "clarify the specific role of anti-inflammatory and antiproliferative treatments in this setting, for example by comparing agents of different classes (corticosteroids, Cox-2 antagonists, and other non-steroidal anti-inflammatory drugs) and by seeking to optimize the duration of therapy and benefit-to-risk ratios."
The editorial writers declared no conflicts of interest.