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DITORIAL COMMENT

rug-Eluting Stentsore Dollars Than Sense?*

unil Garg, MD,†‡ Mark J. Eisenberg, MD, MPH‡§

ontreal, Quebec, Canada

he clinical and economic analysis by Eisenstein et al. (1) inhis issue of JACC: Cardiovascular Interventions is a welcomeddition to the collective literature on the cost-effectiveness ofrug-eluting stents (DES). There are limited trial data regard-

ng this topic, and most appraisals have been based on registryssessments. Eisenstein et al. (1) present the long-term clinicalnd economic analysis of a trial comparing a DES (zotaroli-us, Endeavor, Medtronic CardioVascular, Santa Rosa, Cal-

fornia) versus a bare-metal stent (BMS) (Driver, MedtronicardioVascular). The inclusion of data up to 4 years post-

ndex procedure is particularly important given concerns withate stent thrombosis with DES.

See page 1178

The ENDEAVOR II trial was an international, random-zed, double-blind study that assessed the safety and efficacy ofhe Endeavor DES (2). A total of 1,197 patients with a single,e novo lesion in a native coronary artery were randomized toeceive either the Endeavor (n � 598) or Driver (n � 599)tent. The patients had either clinical evidence of ischemia orpositive functional study and could not have had a myocardial

nfarction in the preceding 72 h. The investigators performedn economic assessment of the patients in the ENDEAVORI trial with Medicare cost weights and quality-of-life adjust-ents applied from secondary sources. They compared the

ifferences through a 4-year follow-up period. They found thathe Endeavor stent significantly reduced the rate of 4-yeararget vessel revascularization (TVR) versus the Driver stent.here was no difference in the rates of death or nonfatalyocardial infarction. These findings are consistent with

revious DES safety studies for Cypher (Cordis, Johnson &ohnson, Bridgewater, New Jersey) and Taxus (Boston Scien-ific, Natick, Massachusetts) stents (3,4).

Editorials published in JACC: Cardiovascular Interventions reflect the views of theuthors and do not necessarily represent the views of JACC: Cardiovascular Interven-ions or the American College of Cardiology.

From the *Division of Cardiology, McGill University Health Centre, and theDepartment of Epidemiology, Biostatistics, and Occupational Health and the

wDivisions of Cardiology and Clinical Epidemiology Jewish General Hospital,cGill University, Montreal, Quebec, Canada.

The primary clinical and economic benefit of a DES is theeduction in follow-up TVR and its associated costs. Aisease-specific cost-effectiveness analysis was performed tossess the incremental costs per TVR avoided. There was an1.1% reduction in TVR. Although the index procedure wasore expensive in the DES group, the lower rates of follow-upVR resulted in DES becoming cost neutral. The 4-year cost ofDES approach was $21,873 versus $22,167 for the BMS group.Prior to the present study, there were 2 other trials that

rospectively examined the cost effectiveness of DES com-ared with BMS in the U.S. The first was conducted as aubstudy of the SIRIUS (Sirolimus-Eluting Balloon ex-andable Stent in the treatment of Patients with De Novoative Coronary Artery Lesions) trial (3), which compared

irolimus-eluting stents with BMS. The second trial was aubstudy of the TAXUS IV trial, which comparedaclitaxel-eluting stents with BMS (4).In the SIRIUS trial, patients randomized to DES had costs

f index hospitalization that were higher than patients ran-omized to BMS. However, patients randomized to BMS hadotal follow-up costs that were higher than patients random-zed to DES. This led to similar cumulative 1-year follow-uposts between the 2 groups. The TAXUS IV trial substudy hadimilar results. Both trials followed patients for only 1 year. Aecently published cost-effectiveness assessment (5) extrapo-ated data from these trials and included the cost of clopidogrelver an additional 2-year period. After including the extra costf clopidogrel to prevent late stent thrombosis, the analysisemonstrated a substantially increased cost for DES. Theuthors concluded that an across-the-board use of DES is notost-effective in the U.S. in terms of cost per quality-adjustedife year (QALY) gained and cost per TVR avoided.

Eisenstein et al. (1) examined their data and noted that thereere no major differences in the utilization of dual antiplatelet

herapy between the 2 groups over the 4 years of the study. Onhe other hand, they were unable to take into account theajor shift that has occurred in the management of patientsith DES since their data were collected. The trial data were

ollected between July 2003 and January 2004, and bothroups were assigned to 12 weeks of dual antiplatelet therapy.n 2004, the risk of late stent thrombosis had not yet beenecognized, and it was considered safe to discontinue dualntiplatelet therapy in patients with Cypher stents at 12eeks and with Taxus stents at 24 weeks. However, follow-

ng the discovery of risk of late stent thrombosis for DES,atients are now maintained on dual antiplatelet therapy forlonger period of time.The investigators demonstrated a statistically insignificant

ifference between the 2 groups with regards to the use of dualntiplatelet therapy over the 4-year period. However, this doesot reflect the current clinical practice of maintaining patients

ith DES on clopidogrel for a minimum of 1 year, and in

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D E C E M B E R 2 0 0 9 : 1 1 8 8 – 9 Editorial Comment

1189

ome cases indefinitely. Prior studies have estimated the costsf such dual antiplatelet therapy to be roughly $2,500 over 2ears (5). If factored over the 4 years of the ENDEAVOR IItudy, this extra expenditure would increase the cost associatedith DES to the point that it would no longer be cost effective.urthermore, the patients who received BMS could havetopped their dual antiplatelet therapy as early as 4 weeks if nooncomitant acute coronary syndrome were present, thusagnifying further the cost differential between the 2 arms.There are extensive data proving DES effectively reduce the

ate of in-stent stenosis and that they are an important tool inhe arsenal of interventional cardiologists. Convincing dataemain absent, however, that DES are cost saving or that theyre cost neutral. A considerable amount of money must bepent for a modest long-term clinical benefit since DES haveo impact on mortality or myocardial infarction rates andecause their effect on quality of life appears modest (6). Givenhe ever-increasing scrutiny on health care expenditures andhe increasingly important need for fiscal responsibility, anll-embracing use of DES cannot be advocated at this time.ES are likely only to be cost effective in highly selected

roups of patients at particularly high risk for restenosis. Givenhe risk of late stent thrombosis and the need for long-termual antiplatelet therapy, future studies should include the costf extended thienopyridine use in order to determine the trueost of DES. In our opinion, a nonselective use of DES

urrently involves more dollars than sense. v

eprint requests and correspondence: Dr. Mark J. Eisenberg,ivisions of Cardiology and Clinical Epidemiology, Sir Mortimer. Davis Jewish General Hospital/McGill University, 3755 Cotete. Catherine Road, Suite A-118, Montreal, Quebec H3T 1E2,anada. E-mail: mark.eisenberg@mcgill.ca.

EFERENCES

. Eisenstein EL, Wijns W, Fajadet J, et al. Long-term clinical and economicanalysis of the endeavor drug-eluting stent versus the driver bare-metalstent: 4-year results from the ENDEAVOR II trial (Randomized Con-trolled Trial to Evaluate the Safety and Efficacy of the Medtronic AVEABT-578 Eluting Driver Coronary Stent in De Novo Native CoronaryArtery Lesions). J Am Coll Cardiol Intv 2009;2:1178–87.

. Fajadet J, Wijns W, Laarman GJ, et al. Randomized, double-blind,multicenter study of the endeavor zotarolimus-eluting phosphorylcholine-encapsulated stent for treatment of native coronary artery lesions. Circula-tion 2006;114:798–806.

. Cohen DJ, Bakhai A, Shi C, et al. Cost-effectiveness of sirolimus-eluting stents from the Sirolimus-Eluting Balloon Expandable Stent inthe Treatment of Patients with De Novo Native Coronary ArteryLesions (SIRIUS) trial. Circulation 2004;110:508–14.

. Bakhai A, Stone GW, Mahoney E, et al. Cost effectiveness of paclitaxel-eluting stents for patients undergoing percutaneous coronary revasculariza-tion: results from the Taxus-IV trial. J Am Coll Cardiol 2006;48:253–61.

. Filion KB, Roy AM, Baboushkin T, et al. Cost-effectiveness ofdrug-eluting stents including the economic impact of late stent throm-bosis. Am J Cardiol 2009;103:338–44.

. Babapulle MN, Joseph L, Belise P, et al. A hierarchical Bayesianmeta-analysis of randomised clinical trials of drug-eluting stents. Lancet2004;364:583–91.

ey Words: cost-effectiveness � drug-eluting stents � target

essel revascularization � QALY � quality-adjusted life year.