Late events, less use of drug-eluting stents?

The study by Handke et al

focuses on one of the most controversial areas of interventional cardiology—the clinical downside of treatment with drug-eluting stents (DES). For the greater part of the past decade, treatment with the Cypher (Cordis Corporation, Miami, Fla) or Taxus (Boston Scientific, Natick, Mass) stents held out hope for a possible "cure" to the Achilles heel of percutaneous coronary intervention, namely, restenosis. Initial studies proved this correct, showing that the use of DES significantly reduced the rate of restenosis and target vessel revascularization compared with bare-metal stents (BMS).^1,2 Although late stent thrombosis was thought to be a possible problem due to delayed re-endothelialization this was not proven until recent reports. This present study addresses the incidence of stent thrombosis occurring more than 1 year after stent implantation in DES versus BMS.

The patient base for the BASKET-LATE study was drawn from the BASKET trial, which randomized 826 patients to either DES or BMS (545 receiving DES and 281 receiving BMS). This patient population was followed for 6 months in the BASKET trial with regard to the incidence of adverse cardiac events. Of these 826 patients, 746 (90.3%) survived the initial 6 months without major adverse cardiac events. These patients formed the basis for the BASKET-LATE trial.

P =

At the 6-month period all patients had clopidogrel therapy withdrawn but were continued on 100 mg of aspirin per day. At the end of the 12-month period after clopidogrel withdrawal (a total time of 18 months after stent implantation), there were 6 cardiac deaths and 2 nonfatal myocardial infarctions (MIs) occurring in patients with DES. There were no deaths and only 3 nonfatal MIs reported in the one-third of patients receiving BMS. The combined end points of cardiac death and nonfatal MI was significantly elevated in the 7- to 18-month period after stent implantation in patients with DES compared with BMS (4.9% vs 1.3%, .01). There was a tendency, however, toward lower restenosis-related target vessel revascularization in patients with DES (4.5%) versus BMS (6.7%). This result did not reach statistical significance.

The total number of clinical events during the 1-year period following clopidogrel withdrawal was 65, including cardiac deaths, nonfatal MI, increasing angina without MI, and angiographically proven subtotal thrombotic obstruction. It was felt that 16 of 65 clinical events (or 25%) were associated with stent thrombosis. The rate for DES was 2 to 3 times higher than for BMS with regards to both angiographically documented stent thrombosis and thrombosis-related clinical events. Due to the low incidence rate these findings were not statistically significantly. Finally late thrombotic events were observed an average of 115 days after discontinuation of clopidogrel.

With the advent of optimal stent deployment as directed by intravascular ultrasound and other modalities along with the use of antiplatelet agents, coronary artery stenting became a viable treatment option for coronary artery disease in the 1990s. The advent and widespread use of DES over the past 5 years has been heralded as the next major therapeutic direction in interventional cardiology. The present study, along with others, points out limitations in the use of DES. However, one can draw a number of "take-home" clinical lessons and implications from these studies.

We must not forget that DES significantly reduce restenosis and target vessel revascularization rates compared with BMS. This is especially true in select patient populations, such as those with diabetes and those having small-vessel coronary artery disease. Thus, for these patients the continued use of DES seems very reasonable, although concomitant long-term use of clopidogrel would also be necessary to ensure a lower risk of MI and/or death. The time frame for this long-term use is still uncertain, and must be balanced against the increased risk of hemorrhage and high costs of prolonged dual antiplatelet therapy. At the very least, clopidogrel use for a minimum of 1 year and possibly longer is mandated.

Although BMS have been used less frequently in recent years, these may again become more common in certain circumstances. These clinical settings may include stenting in larger coronary arteries (3.5 mm or greater) and in patients without diabetes. Finally, patients who have contraindications to dual antiplatelet therapy, or who may be noncompliant with clopidogrel therapy for financial reasons, may be best treated with optimal deployment of BMS. Although this shift in practice pattern may not be optimal, in light of the recent studies on late stent thrombosis with DES, this may be necessary until the next generation of endovascular treatments, including bioabsorbable stents and new and different stent platforms, make their appearance.