More Support for Long-Term Plavix to Improve Stent Safety

DURHAM, N.C., Dec. 5 -- Extending dual antiplatelet therapy with aspirin and Plavix (clopidogrel) to six months or longer significantly reduced the risk of death or myocardial infarction for patients given drug-eluting stents, researchers here reported.

But there is no evidence to suggest the appropriate duration of Plavix and colleagues therapy, Eric L. Eisenstein, D.B.A., of Duke, and colleagues, reported today in an early online release by the Journal of the American Medical Association.

And there was no evidence that duration of Plavix treatment affected death or MI risk for patients who received bare metal stents.

Dr. Eisenstein and colleagues conducted an observational study of 4,666 patients who had stenting procedures at Duke from January 1, 2002 through July 31, 2005 and were followed at six, 12 and 24 months through September 7, 2006.

Bare metal stents were implanted in 3,165 patients and drug-eluting stents in 1,501.

At six months 1,216 drug-eluting stent patients were event free. Of those 637 were still taking Plavix and 579 had stopped Plavix.

Among the findings:

• Plavix use at six months was a significant predictor of lower adjusted rates of death (2.0% with versus 5.3% without; difference -3.3%; 95% CI-6.3% to -0.3%; P=0.03) at 24 months.
• Plavix use at six months was also a significant predictor of death or MI (3.1% versus 7.2%; difference -4.1%; 95% CI -7.6% to -0.6%; P=0.02) at 24 months.

The apparent benefit of Plavix continued for those who were event-free at 12 months. The 252 patients who remained on Plavix had a lower death rate at 24 months (0% versus 3.5%; differnce-3.5%; 95% CI-5.9% to -1.1%; P=0.004) than the 276 patients who stopped taking Plavix.

Likewise Plavix use at one year was predictive of lower death and MI rate at 24 months-0% versus 4.5%; difference -4.5%; 95% CI, -7.1% to -1.9% P

Yesterday, the Journal of the American College of Cardiology weighed with 18-month results from the Basel Stent Kosten-Effecktivits Trial (BASKET) investigators. That study reported an increase in events when Plavix was stopped beginning at seven months after percutaneous coronary intervention.

The JACC study included an editorial by Robert A. Harrington, M.D., and Robert M. Califf, M.D., two Duke researchers who are also co-authors of today's JAMA study.

Researchers and regulators have turned their focus to drug-eluting stents following reports that the stents, which dramatically reduced the problem of in-stent restenosis, may increase the rate of late thrombosis.

The controversy started slowly last March with a single report from the BASKET investigators at the American College of Cardiology meeting. That report, which suggested a higher late thrombosis rate for drug-eluting stents, ignited a long fuse for a controversy that finally exploded at the European Society of Cardiology/World Cardiology Congress in Barcelona in September.

Following the ESC meeting, at which the 18 month results of BASKET-LATE were reported, along with two meta-analyses of published trials of drug-eluting stents, and data from two registries, those doubting, and defending, the safety of drug-eluting stents began firing off editorials in leading medical journals.

The controversy picked up steam when the FDA announced plans for the safety hearing. The drug-eluting stent controversy dominated every day of the week-long Transcathter Therapeutics (TCT) meeting in October.

As one measure of the drama that is expected to unfold at the FDA hearing, the briefing books sent to panel members contained 2,500 pages of printed material, which is about three times the amount of briefing material normally distributed to FDA advisory panel members.

The Duke study was funded under contract from the Agency for Healthcare Research and Quality.

Dr. Eisenstein's financial disclosures included Medtronic Vascular. His coauthors reported financial support including grants, consulting fees, and honoraria from the National Heart Lung and Blood Institute, the Agency for Healthcare Research and Quality, Procter & Gamble, Pfizer, Medtronic, Alexion Pharmaceuticals, Medicure, Medtronic Vascular, Bristol-Myers Squibb, Novartis, AstraZeneca, Aventis, Boston Scientific, Cordis Corp., Sanofi-Aventis, Abbott Vascular, Conor Medsystems Inc., Guidant Corporation, Advanced Cardiovascular Systems, and Terumo Medical Corporation.