17 August 2007
MedWire News: Adjunctive treatment with the cyclo-oxygenase (COX)-2 inhibitor celecoxib in patients undergoing angioplasty with stenting can reduce restenosis and the need for revascularization, preliminary clinical findings indicate.
The study authors say the drug appears to be safe in this setting, but commentators cautioned that concerns remain over the risks of destabilized atherosclerotic disease and gastrointestinal side effects associated with COX-2 inhibitors.
Celecoxib is commonly used as an anti-inflammatory agent but also has antiproliferative, pro-apoptotic, and antitumor effects, explain Hyo-Soo Kim (Seoul National University Hospital, South Korea) and team in the The Lancet.
Having found that celecoxib inhibits proliferation and increases apoptosis of vascular smooth muscle cells in vitro, and inhibits neointimal hyperplasia after angioplasty in animals, Kim and colleagues tested whether it would have similar effects in the clinical setting.
The researchers enrolled 274 patients with angina or a positive stress test and native coronary artery lesions who were suitable for implantation of paclitaxel-eluting stents. All patients received aspirin and clopidogrel before the procedure and aspirin 100 mg daily was taken indefinitely and clopidogrel 75 mg taken daily for at least 6 months after the procedure.
The patients were randomly assigned to receive celecoxib 400 mg just before intervention, and 200 mg twice daily thereafter for 6 months, or placebo.
The mean in-stent late luminal loss at 6 months - the primary endpoint - was significantly smaller in celecoxib-treated patients than the control group (0.49 vs 0.75 mm, p<0.0001).
In-segment late luminal loss was also lower in the celecoxib group (0.33 vs 0.56 mm, p=0.001), as were both in-stent and in-segment restenosis rates (p=0.007 and p=0.001, respectively).
The rate of major adverse cardiac events was lower in the first 6 months after stent implantation in the celecoxib group than in the placebo group, at 5% versus 16% (relative risk [RR]=0.34, p=0.005). This difference was largely due to a reduced need for target lesion revascularization among patients who received celecoxib (5% vs 15%, RR=0.35; p=0.008).
The rate of clinically driven target lesion revascularization was also lower in celecoxib-treated patients, the authors note (5% vs 12%, RR=0.40; p=0.036).
In an accompanying Comment article, Francesco Pelliccia and Vincenzo Pasceri (Ospedale San Filippo Neri, Rome, Italy) said that the strategy suggested by Kim et al is “appealing” and could easily be introduced into clinical practice.
However, they noted, safety of the drug needs to be confirmed in studies powered to assess risk of myocardial infarction and cardiac death, and the gastrointestinal tolerability of chronic therapy with both celecoxib and dual antiplatelet therapy “might also be a drawback.”
Nevertheless they concluded that the study “underscores that systemic therapy might still have a role in prevention of restenosis, even in the era of drug-eluting stents.”
Lancet 2007; 370: 567-574 [标签:content1][标签:content2]
作者:admin@医学,生命科学 2011-02-17 18:04