Conflicting reports of drug-eluting stent safety add to growing controversy

November 13, 2006

A series of analyses offers no consensus on the safety of drug-eluting stents (DES) compared with bare metal stents. Depending on the study, DES either result in an increase in major adverse coronary events (MACE) or a decrease in subsequent need for coronary artery bypass graft (CABG) surgery and repeat percutaneous coronary intervention without an excess of adverse clinical events.

A series of analyses offers no consensus on the safety of drug-eluting stents (DES) compared with bare metal stents. Depending on the study, DES either result in an increase in major adverse coronary events (MACE) or a decrease in subsequent need for coronary artery bypass graft (CABG) surgery and repeat percutaneous coronary intervention without an excess of adverse clinical events,

In a registry of 9,043 patients undergoing intracoronary stenting at LDS Hospital/University of Utah, the rates of MACE, defined as death, nonfatal myocardial infarction, target vessel revascularization, or CABG were assessed out to 3 years for patients receiving either bare metal or DES.

"After the first year, there were statistically worse outcomes with drug-eluting stents versus bare metal stents," said Joseph B. Muhlestein, MD, co-author of the study.

The risk of MACE was increased by 36% ( P <.0001) and all-cause death was 93% more likely ( P <.0001) with DES, Dr. Muhlestein said. Furthermore, although the DES reduced the rate of target lesion revascularization, non-target lesion-related revascularization was more common with the DES, resulting in a significant increase in all forms of coronary revascularization at 3 years.

The DES may have contributed to an acceleration of atherosclerosis in nonstented coronary segments, Dr. Muhlestein said, a contention supported by other studies that have demonstrated evidence of endothelial dysfunction in coronary segments distal to the DES.

David O. Williams, MD, from Rhode Island Hospital in Providence, R.I., presented findings from a National Heart, Lung, and Blood Institute (NHLBI) registry of 3,223 patients who received either a bare metal stent (October 2001 to March 2002) or a DES (February to May 2004).

At 1 year, there was no difference in the rate of death or myocardial infarction (MI) between the 2 groups, while the need for CABG was significantly less with the DES compared with the bare metal stent (1.2% vs. 3.1%; P <.001). Target vessel revascularization, repeat revascularization, and MACE were all significantly less likely in the DES group.

Sidney Smith, MD, at the University of North Carolina, Chapel Hill, N.C., and past president of the American Heart Association (AHA), pointed out that the meta-analyses presented in September at the World Cardiology of Congress (WCC) meeting in Barcelona, Spain, showed that late stent thrombosis seemed to be a problem with the DES. Dr. Smith noted that Dr. Williams' follow-up was only 1 year, whereas Dr. Muhlestein's analysis followed patients for MACE at 3 years.

A third study of 505 patients undergoing primary angioplasty and treated with either bare metal or DES found an early advantage to DES with respect to target vessel revascularization. However, DES (either the sirolimus- or the paclitaxel-eluting stent) were no longer significantly superior to bare metal stents after 3 years of follow-up in reducing MACE, said lead investigator Joost Daemen, MD, from Thoraxcenter, Erasmus Medical Center, Rotterdam, Netherlands. Mortality was comparable between the bare metal stents and DES at 3 years.

"Fifty percent of target vessel revascularizations were performed after the first year of follow-up due to stent thrombosis, and 100% of the MIs after the first year were due to stent thrombosis" Dr. Daemen said.