Coronary Drug-Eluting Stent Safety Diminishes Over Time

By Peggy Peck ,

CALGARY, Alberta, 27 dec 2008 -- Three years after stent placement, the risk of death or revascularization associated with drug-eluting stents was significantly greater than the risk among patients treated with bare metal stents, researchers here reported. After 12 months, both mortality and repeat revascularization rates were about 25% lower for those receiving drug-eluting stents compared with patients given bare-metal stents, Andrew C. Philpott, M.D., of the University of Calgary, and colleagues, reported online in the Canadian Medical Association Journal. But, they added, by the end of year three, the relative risk of death or repeat revascularization was more than twice as great for drug-eluting stents. "The adjusted relative risk of the composite outcome of death or repeat revascularization associated with drug-eluting stents relative to bare-metal stents was 0.73 early in the first year of follow-up," they wrote. "It then rose gradually over time, to a peak of 2.24 at three years." Dr. Philpott and colleagues used several methods to conduct a time-dependent analysis, and each time "there was an initial pattern of decreased risk of events with drug-eluting stents, followed by a gradual transition over time toward better outcomes with the bare-metal stents." But despite the increase in relative risk in the time-dependent analysis, the long-term survival for drug-eluting stents was favorable overall, and "we did not detect an overwhelming increase in the risk of death among patients, who received this type of stent," they wrote. And while the time-dependent analysis revealed an increased risk with drug-eluting stents, "we did not observe any notable survival drops or clusters of deaths." The findings were derived from data from 6,440 consecutive patients in the APPROACH (Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease) registry. All patients were treated from April 1, 2003 through March 31, 2006. Drug-eluting stents were used in 1,120 patients versus 5,320 patients who received bare-metal stents. As with other registry studies, patients who received drug-eluting stents were sicker -- 32.8% with diabetes versus 20.8% with bare-metal stent patients (P 0.001) and 7.4% versus 5.0 had kidney disease (P =0.001). The one-year mortality rate was 3.0% in the drug-eluting stent group versus 3.7% in the bare-metal group, and 12.0% of the drug-eluting stent patients versus 15.8% of the bare-mental stent patients reached the combined endpoint of death or repeat revascularization by 12 months. Dr. Philpott cautioned that because the comparison was not a randomized, controlled trial the findings might reflect selection bias; thus, they should not be interpreted as an efficacy analysis. Additionally, the analysis did not include information on long-term medication use, so the investigators could "only speculate on the potential role of discontinuation of antiplatelet therapy on the later onset of adverse outcomes inpatients with drug-eluting stents." And because they included repeat revascularization in the composite endpoint, "we probably captured procedures done because of disease progression rather than restenosis." The study was initially funded with a grant from the W. Garfield Weston Foundation. The ongoing operation of the APPROACH registry was funded by the Canadian Cardiovascular Outcomes Research Team, the Canadian Institutes of Health, and the Province Wide Services Committee of Alberta Health and Wellness. Industry sponsors were Merck Frosst Canada, Roche Canada, Eli Lilly Canada, Bristol-Myers Squibb, Philips Medical Systems Canada, Searle Pharmaceuticals, Boston Scientific, and Cordis, a Johnson & Johnson Company. Dr. Philpott made no financial disclosures.

Primary source: Canadian Medical Association Journal Source reference: Philpott, AC et al "Long-term outcomes of patients receiving drug-eluting stents" Can Med Assoc J 2008; DOI: 10.1503/cmaj.080050.