Current issues of ACP Journal Club are published in Annals of Internal Medicine


Drug-eluting stents increased risk for late cardiac death or myocardial infarction more than bare-metal stents


ACP J Club. 2007 May-Jun;146:67. doi:10.7326/ACPJC-2007-146-3-067

Related Content in the Archives
Review: Drug-eluting stents for coronary artery disease do not reduce mortality more than bare-metal stents

Clinical Impact Ratings

Cardiology: 5 stars

Source Citation

Pfisterer M, Brunner-La Rocca HP, Buser PT, et al. Late clinical events after clopidogrel discontinuation may limit the benefit of drug-eluting stents: an observational study of drug-eluting versus bare-metal stents. J Am Coll Cardiol. 2006;48:2584-91. [PubMed ID: 17174201]



Are drug-eluting stents (DESs) more effective than bare-metal stents (BMSs) in reducing major cardiac events in patients with coronary artery disease who discontinue antiplatelet therapy with clopidogrel 6 months after stent placement?


Design: Cluster randomized controlled trial (Basel Stent Kosten-Effektivitäts Trial Late Thrombotic Events [BASKET-LATE]).

Allocation: {Concealed}†.*

Blinding: Blinded ({data collectors}† and outcome assessors).*

Follow-up period: 18 months.

Setting: University hospital in Basel, Switzerland.

Patients: BASKET included 826 patients (mean age 64 y, 79% men) with coronary artery disease who were being treated with percutaneous coronary intervention (PCI) and stenting. Patients with target vessel diameter ≥ 4 mm or restenotic lesions were excluded. The BASKET-LATE follow-up study analyzed data on 743 patients who survived 6 months after the procedure without a major cardiac event.

Intervention: DES (using sirolimus or paclitaxel) (n = 499) or BMS (n = 244). Patients were randomized by treatment day to 1 of the 3 stents, and all received maintenance clopidogrel, 75 mg/d for 6 months, in addition to aspirin, 100 mg/d, and statin therapy indefinitely.

Outcomes: Late (7 to 18 mo after stent implantation) major cardiac events, including cardiac death, nonfatal myocardial infarction (MI), and restenosis-related target vessel revascularization (TVR).

Patient follow-up: 98% (89% of patients in BASKET) (intention-to-treat analysis).

Main results

DESs reduced risk for major cardiac events in the first 6 months (Table). At 7 to 18 months, risk for cardiac death and MI was higher in the DES group than in the BMS group (Table); groups did not differ for TVR or total late major cardiac events (Table). Over the 18-month follow-up, risk for cardiac death or MI did not differ between groups, but risk for TVR was lower in the DES group (Table). Late stent thrombosis-related events (25% of total late events) were twice as likely with a DES {P = 0.23}‡ and occurred at a median 116 days (range 15 to 362 d) after discontinuation of clopidogrel.


In patients with coronary artery disease, increased risk for late cardiac death or myocardial infarction following discontinuation of antiplatelet clopidogrel therapy 6 months after stent placement may offset the early benefits of drug-eluting stents over bare-metal stents.

*See Glossary.

†Information provided by author.

‡Calculated from data in article.

Source of funding: Basel Cardiac Research Foundation.

For correspondence: Dr. M. Pfisterer, University Hospital, Basel, Switzerland. E-mail

Table. Drug-eluting stents (DESs) vs bare-metal stents (BMSs) in coronary artery disease at 18 months§

Outcomes Follow-up DESs BMSs RRR/RRI (95% CI) NNT/NNH (CI)
Major cardiac event 6 mo|| 7.2% 12% RRR: 41% (9 to 62) NNT: 21 (11 to 120)
7 to 18 mo 9.3% 7.9% RRI: 18% (−29 to 96) Not significant
Cardiac death or MI 7 to 18 mo 4.9% 1.3% RRI: 289% (27 to 1109) NNH: 28 (17 to 112)
18 mo 8.4% 7.5% RRI: 13% (−31 to 85) Not significant
TVR 7 to 18 mo 4.5% 6.7% RRR: 33% (−24 to 64) Not significant
18 mo 7.5% 12% RRR: 36% (1 to 58) NNT: 24 (12 to 974)

§Major cardiac event = cardiac death, nonfatal myocardial infarction (MI), or restenosis-related target vessel revascularization (TVR). Other abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article.
||Kaiser C, Brunner-LaRocca HP, Buser PT, et al. Lancet 2005;366:921-9. 16154019


DESs have dramatically decreased the need for coronary artery bypass graft (CABG) surgery and repeated PCI. However, late stent thrombosis is a small but important risk with DESs because it is commonly associated with sudden death or acute MI

The clinical occurrence of stent thrombosis after stent implantation can be defined as acute (< 24 h), subacute (1 to 30 d), late (30 d to 1 y), or very late (> 1 y). The clinical diagnosis of stent thrombosis can be defined as “definite” if proven angiographically or pathologically, “probable” if an MI occurs in the distribution of the stented artery, or “possible” if death is unexplained (1). Risk for subacute stent thrombosis is about 1% for both DESs and BMSs, but risk for very late stent thrombosis continues for at least 4 years with DESs at a rate of 2 to 4 events/1000 patients per year (1−3). The presumed cause is delayed or incomplete endothelialization of the stent struts. The unanswered question is whether the decrease in risk for death and MI from avoiding CABG, restenosis, or repeated PCI is greater than the risk for death or MI from late stent thrombosis.

Pfisterer and colleagues compared the incidence of late clinical events among patients assigned to either a DES or a BMS. The study suggested an early reduction in death or MI from less TVR with DESs but a late increase in death or MI from stent thrombosis after discontinuation of clopidogrel therapy. The meta-analysis by Nordmann and colleagues, as well as several subsequent reports that have been used to support current DES labeling (1−3), showed no long-term increase in death or MI rates with 3 to 6 months of dual antiplatelet therapy. Therefore, the small increase in risk for stent thrombosis with DES implantation does not outweigh its benefit compared with BMS implantation. However, ambiguity remains regarding the role of off-label DES implantation in complicated patients (e.g., those with diabetes, acute MI, or multivessel coronary disease) and for patients with complex coronary lesions (e.g., those with longer length, smaller diameter, bifurcations, or vein grafts) in which risk for late stent thrombosis is increased. Furthermore, because there has been no controlled clinical trial examining DESs in these complicated circumstances, no comparative data exist regarding risk for death or MI with such alternative treatments as CABG or BMS.

Although premature discontinuation of dual antiplatelet therapy (< 3 to 6 mo) is a risk factor for stent thrombosis and many cases of stent thrombosis occur despite therapy, the optimal duration of antiplatelet therapy is unknown. No data exist showing the benefit of prolonged dual antiplatelet therapy after 6 months, but 12 months of therapy after DES implantation has been recommended recently, if the bleeding risk is low (4, 5). Similarly, no data exist to support indefinite dual antiplatelet therapy, an impractical general strategy given the cost and attendant risk for bleeding. Consequently, DESs should be avoided in the presence of financial barriers to continuing prolonged dual antiplatelet therapy, social barriers that may limit patient compliance, or medical issues involving bleeding risks or the need for invasive or surgical procedures in the following year that would interrupt antiplatelet therapy.

Patients should understand the benefits and risks of all treatment options and be able to commit to uninterrupted dual antiplatelet therapy for 1 year before DES implantation can be recommended. Interventionalists should thoughtfully select patients for a DES and use optimal implantation techniques. Unfortunately, industry-funded observational registry studies are not likely to clarify the issue of long-term DES safety, and the lack of randomized trials in complicated patients with complex coronary lesions further precludes evidence-based comparisons between DES and BMS, CABG, and medical therapy. The solution will probably come from newer stent iterations with antithrombotic coatings, bioabsorbable polymers, or biodegradable struts.

Eric R. Bates, MD
University of Michigan
Ann Arbor, Michigan, USA


1. Mauri L, Hsieh WH, Massaro JM, et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med. 2007;356:1020-9. [PubMed ID: 17296821]

2. Bavry AA, Kumbhani DJ, Helton TJ, et al. Late thrombosis of drug-eluting stents: a meta-analysis of randomized clinical trials. Am J Med. 2006;119:1056-61. [PubMed ID: 17145250]

3. Stone GW, Moses JW, Ellis SG, et al. Safety and efficacy of sirolimus- and paclitaxel-eluting coronary stents. N Engl J Med. 2007;356:998-1008. [PubMed ID: 17296824]

4. Hodgson JM, Stone GW, Michael Lincoff A, et al. Late stent thrombosis: considerations and practical advice for the use of drug-eluting stents: a report from the Society for Cardiovascular Angiography and Interventions drug-eluting stent task force. Catheter Cardiovasc Interv. 2007;69:327-33. [PubMed ID: 17219373]

5. Grines CL, Bonow RO, Casey DE Jr., et al. Prevention of premature discontinuation of dual antiplatelet therapy in patients with coronary artery stents: a science advisory from the American Heart Association, American College of Cardiology, Society for Cardiovascular Angiography and Interventions, American College of Surgeons, and American Dental Association, with representation from the American College of Physicians. J Am Coll Cardiol. 2007;49:734-9. [PubMed ID: 17291948]