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Comparison of Effectiveness of Bare Metal Stents Versus Drug-Eluting Stents in Large (≥3.5 mm) Coronary Arteries

2007; Elsevier BV; Volume: 99; Issue: 5 Linguagem: Inglês

10.1016/j.amjcard.2006.09.105

1879-1913

Daniel Steinberg, Sundeep Mishra, Aamir Javaid, Tina L. Pinto Slottow, Ashesh N. Buch, Probal Roy, Teruo Okabe, Kimberly A. Smith, Rebecca Torguson, Zhenyi Xue, Augusto D. Pichard, Lowell F. Satler, Kenneth M. Kent, William O. Suddath, Ron Waksman,

Acute Myocardial Infarction Research

Drug-eluting stents (DESs) are superior to bare metal stents (BMSs) in decreasing restenosis rates across a wide range of patient and lesion subsets. However, widespread utilization of DESs raises concerns with regard to risks of prolonged dual antiplatelet therapy, the potential for late adverse events such as late thrombosis, and cost. Vessel diameter and lesion length have been previously identified as predictors for restenosis for DESs and BMSs. This study compared the clinical outcomes of DESs versus BMSs in large coronary arteries (≥3.5 mm). A cohort of 233 patients who underwent single-vessel angioplasty with DES implantation in large vessels was compared with 233 propensity-matched patients who received BMSs in vessels with similar reference vessel diameters. Clinical outcomes at 30 days, 6 months, and 1 year were compared between groups. Baseline clinical and procedural characteristics were similar. Target lesion revascularization and target vessel revascularization rates and the incidence of major adverse cardiac events were low and comparable between the 2 groups at all follow-up intervals. At 1 year, the primary outcome occurred in 8.5% of patients with DESs and 7.7% of patients with BMSs (p = 0.80). There were no episodes of subacute stent thrombosis or late thrombosis in either group. In conclusion, implantation of DESs in large coronary arteries confers no additional benefit compared with BMSs, and the 2 approaches are associated with equally favorable clinical outcomes at 1 year. Drug-eluting stents (DESs) are superior to bare metal stents (BMSs) in decreasing restenosis rates across a wide range of patient and lesion subsets. However, widespread utilization of DESs raises concerns with regard to risks of prolonged dual antiplatelet therapy, the potential for late adverse events such as late thrombosis, and cost. Vessel diameter and lesion length have been previously identified as predictors for restenosis for DESs and BMSs. This study compared the clinical outcomes of DESs versus BMSs in large coronary arteries (≥3.5 mm). A cohort of 233 patients who underwent single-vessel angioplasty with DES implantation in large vessels was compared with 233 propensity-matched patients who received BMSs in vessels with similar reference vessel diameters. Clinical outcomes at 30 days, 6 months, and 1 year were compared between groups. Baseline clinical and procedural characteristics were similar. Target lesion revascularization and target vessel revascularization rates and the incidence of major adverse cardiac events were low and comparable between the 2 groups at all follow-up intervals. At 1 year, the primary outcome occurred in 8.5% of patients with DESs and 7.7% of patients with BMSs (p = 0.80). There were no episodes of subacute stent thrombosis or late thrombosis in either group. In conclusion, implantation of DESs in large coronary arteries confers no additional benefit compared with BMSs, and the 2 approaches are associated with equally favorable clinical outcomes at 1 year. Compared with bare metal stents (BMSs), drug-eluting coronary stents (DESs) have been shown to decrease restenosis across a wide range of coronary lesions and patient subsets.1Morice M.C. Serruys P.W. Sousa J.E. Fajadet J. Ban Hayashi E. Perin M. Colombo A. Schuler G. Barragan P. Guagliumi G. Molnar F. Falotico R. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization.N Engl J Med. 2002; 346: 1773-1780Crossref PubMed Scopus (3905) Google Scholar, 2Moses J.W. Leon M.B. Popma J.J. Fitzgerald P.J. Holmes D.R. O'Shaughnessy C. Caputo R.P. Kereiakes D.J. Williams D.O. Teirstein P.S. Jaeger J.L. Kuntz R.E. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.N Engl J Med. 2003; 349: 1315-1323Crossref PubMed Scopus (4098) Google Scholar, 3Schofer J. Schluter M. Gershlick A.H. Wijns W. Garcia E. Schampaert E. Breithardt G. Sirolimus-eluting stents for treatment of patients with long atherosclerotic lesions in small coronary arteries: double-blind, randomised controlled trial (E-SIRIUS).Lancet. 2003; 362: 1093-1099Abstract Full Text Full Text PDF PubMed Scopus (955) Google Scholar, 4Stone G.W. Ellis S.G. Cox D.A. Hermiller J. O'Shaughnessy C. Mann J.T. Turco M. Caputo R. Bergin P. Greenberg J. Popma J.J. Russell M.E. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.N Engl J Med. 2004; 350: 221-231Crossref PubMed Scopus (2659) Google Scholar, 5Dawkins K.D. Grube E. Guagliumi G. Banning A.P. Zmudka K. Colombo A. Thuesen L. Hauptman K. Marco J. Wijns W. et al.Clinical efficacy of polymer-based paclitaxel-eluting stents in the treatment of complex, long coronary artery lesions from a multicenter, randomized trial: support for the use of drug-eluting stents in contemporary clinical practice.Circulation. 2005; 112: 3306-3313Crossref PubMed Scopus (300) Google Scholar, 6Stone G.W. Ellis S.G. Cannon L. Mann J.T. Greenberg J.D. Spriggs D. O'Shaughnessy C.D. DeMaio S. Hall P. Popma J.J. Koglin J. Russell M.E. Comparison of a polymer-based paclitaxel-eluting stent with a bare metal stent in patients with complex coronary artery disease: a randomized controlled trial.JAMA. 2005; 294: 1215-1223Crossref PubMed Scopus (740) Google Scholar The benefit of DES is limited to restenosis because no significant decreases in myocardial infarction or mortality have been demonstrated.7Roiron C. Sanchez P. Bouzamondo A. Lechat P. Montalescot G. Drug eluting stents: an updated meta-analysis of randomised controlled trials.Heart. 2006; 92: 641-649Crossref PubMed Scopus (191) Google Scholar, 8Babapulle M.N. Joseph L. Belisle P. Brophy J.M. Eisenberg M.J. A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents.Lancet. 2004; 364: 583-591Abstract Full Text Full Text PDF PubMed Scopus (613) Google Scholar In addition, widespread utilization of DES raises important safety and cost concerns.9Pfisterer M. Brunner-La Rocca H.P. Buser P.T. Rickenbacher P. Hunzker P. Mueller C. Jeger R. Bader F. Oswald C. Kaiser C. 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: 2584-2591Abstract Full Text Full Text PDF PubMed Scopus (1278) Google Scholar Elucidation of patient or lesion subsets treated by BMSs and DESs with equivalent long-term efficacy represents an attractive goal. In pivotal DES trials, lesion diameter was an important predictor of benefit with DESs,2Moses J.W. Leon M.B. Popma J.J. Fitzgerald P.J. Holmes D.R. O'Shaughnessy C. Caputo R.P. Kereiakes D.J. Williams D.O. Teirstein P.S. Jaeger J.L. Kuntz R.E. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.N Engl J Med. 2003; 349: 1315-1323Crossref PubMed Scopus (4098) Google Scholar and in TAXUS-IV, the benefit of DESs was confined to lesions 3.5 mm with DESs with 233 propensity-matched patients who received BMSs in similarly sized vessels. Propensity score matching was performed to match baseline high-risk characteristics of the 2 respective groups (DES and BMS). These high-risk factors included presentation with unstable angina, renal insufficiency, left anterior descending artery, proximal or ostial location, saphenous vein graft, in-stent restenosis, and lesion type C. The DES population consisted of 141 patients who received sirolimus-eluting stents (Cypher, Cordis, Miami Lakes, Florida) and 92 patients who received paclitaxel-eluting stents (Taxus, Boston Scientific, Natick, Massachusetts). All indications for stent use (elective use to optimize angiographic results and decrease late restenosis, provisional use to treat suboptimal primary device result, or urgent use to treat abrupt or threatened vessel closure) were included in this study. After the initial balloon angioplasty or ablative procedure, coronary stents were implanted according to standard procedure. At the operator's discretion, intravascular ultrasound was used to ensure optimal stent expansion and apposition. Before the procedure, all patients received orally 325 mg of aspirin and 300 to 600 mg of clopidogrel (at the operator's discretion). Procedural anticoagulation consisted of bivalirudin (bolus of 0.75 mg/kg after sheath insertion, followed by an intravenous infusion of 1.75 mg/kg/hour for the duration of the procedure) or weight-adjusted unfractionated heparin to achieve an activated clotting time of 250 to 300 seconds (Hemochron, International Technidyne, Edison, New Jersey). Glycoprotein IIb/IIIa inhibitors were administered at the operator's discretion. After the procedure, 325 mg/day of aspirin was continued indefinitely, and clopidogrel was maintained for 4 weeks in patients with BMSs and encouraged for ≥6 months in patients with DESs. All patients routinely underwent 12-lead electrocardiography before and after PCI to detect procedure-related ischemic changes and/or the presence of new pathologic Q waves. Blood samples at 6 and 24 hours before and after PCI were drawn to assess creatine kinase-MB isoenzyme. If creatine kinase-MB was increased above the reference range (4 mg/dl), measurements were repeated every 8 hours until it returned to below the reference range. Baseline clinical information, angiographic features, in-hospital complications, and clinical outcomes at follow-up were recorded and entered into a dedicated computerized database. Independent chart audits by trained quality assurance medical personnel were used. Study end points were in-hospital complications including death, myocardial infarction, bleeding complications, vascular complications, and the composite end point of major adverse cardiovascular events, including death, Q-wave myocardial infarction, and urgent revascularization. Clinical follow-up with respect to major adverse cardiac events occurred again at 30 days, 6 months, and 1 year. A dedicated data-coordinating center (Data Center, MedStar Research Institute, Washington, DC) performed all data management and analysis. Prespecified clinical and laboratory data during hospitalization periods were obtained from hospital charts and reviewed by independent research personnel who were unaware of the study objectives. Clinical follow-up included review of pertinent medical records and telephone contact at 30 days, 6 months, and 1 year with adjudication of events by independent research personnel. A large coronary vessel was defined as ≥3.5 mm in diameter. Angiographic success was defined as 30 days after PCI. Hypertension was defined as previously diagnosed hypertension and/or treated with medication or currently being treated with diet and/or medication by a physician. The definition of hypercholesterolemia included patients with a previously documented diagnosis of hypercholesterolemia. The patient could have been treated with diet or medication. The definition did not include high triglyceride levels. All statistical analyses were performed with SAS 8 (SAS Institute, Cary, North Carolina). Results are presented as means ± SDs for continuous variables and as percentages for categorized variables. Differences in continuous variables between groups were compared by t test. Proportions were compared by chi-square test or Fisher's exact test when appropriate. A p value <0.05 was considered statistically significant. Baseline clinical and procedural characteristics are listed in Table 1, Table 2. There were no significant background differences in patients. From a procedural standpoint, patients in each group were also similar with regard to lesion location and complexity. However, patients with BMSs received stents that had wider diameters (3.88 ± 1.76 mm for BMS vs 3.57 ± 1.09 mm for DES, p = 0.024) and were longer (16.0 ± 7.3 mm for BMS vs 19.9 ± 6.1 mm for DES, p <0.001). Rotational atherectomy was performed more frequently in the BMS group (3.0% of BMS group vs 1.2% of DES group, p = 0.05).Table 1Baseline clinical characteristics of the study populationVariableBMS Group (n = 233)DES Group (n = 233)p ValueMen168 (72%)170 (73%)0.78Age (yrs) (mean ± SD)63 ± 1265 ± 110.12Diabetes mellitus72 (31%)82 (35%)0.34Insulin-dependent diabetes mellitus26 (11%)26 (11%)1.00Hypertension175 (75%)184 (79%)0.31Hypercholesterolemia191 (82%)193 (83%)0.89Chronic renal insufficiency31 (13%)34 (15%)0.69Smoker49 (21%)38 (16%)0.19Unstable angina pectoris144 (62%)141 (61%)0.78Acute myocardial infarction42 (18%)35 (15%)0.41Cardiogenic shock5 (2%)4 (1.7%)0.75Ejection fraction (mean ± SD)0.47 ± 0.130.48 ± 0.140.43 Open table in a new tab Table 2Procedural characteristics of the study populationVariableBMS Group (n = 233, 287 lesions)DES Group (n = 233, 336 lesions)p ValueLeft anterior descending artery83 (29%)100 (30%)0.86Left circumflex artery47 (16%)54 (16%)0.93Right coronary artery99 (35%)121 (36%)0.67Left main artery8 (3%)5 (1.5%)0.26Saphenous vein graft49 (17%)54 (16%)0.75In-stent restenosis55 (19%)50 (15%)0.16Type C lesion69 (24%)61 (18%)0.10Multiple lesions36 (15.7%)35 (32.8%)<0.0001Stent diameter (mm) mean ± SD3.88 ± 1.763.57 ± 1.090.024Stent length (mm) mean ± SD16.0 ± 7.3219.9 ± 6.14 3.5 mm in diameter represent a low-risk population in whom BMSs confer a similarly low event rate as DESs. Clinically driven target lesion revascularization rates at 1 year (3.5% for BMSs vs 3.4% for DESs) were similarly low in the 2 populations. Stent thrombosis did not occur in either group, despite thienopyridine discontinuation after 1 month in the BMS group and after ≥6 months in the DES group. Our findings are congruent with previous research. Vessel diameter influences restenosis rates with BMSs,10Hoffmann R. Mintz G.S. Coronary in-stent restenosis—predictors, treatment and prevention.Eur Heart J. 2000; 21: 1739-1749Crossref PubMed Scopus (213) Google Scholar and in the SIRolImUS-coated stent in treatment of patients with de novo coronary artery lesions (SIRIUS) trial, multivariate analysis demonstrated an increased risk of restenosis with smaller vessel diameters.2Moses J.W. Leon M.B. Popma J.J. Fitzgerald P.J. Holmes D.R. O'Shaughnessy C. Caputo R.P. Kereiakes D.J. Williams D.O. Teirstein P.S. Jaeger J.L. Kuntz R.E. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery.N Engl J Med. 2003; 349: 1315-1323Crossref PubMed Scopus (4098) Google Scholar Further, subgroup analysis in TAXUS-IV demonstrated that the significant benefit of DESs over BMSs was limited to vessels <3.0 mm.4Stone G.W. Ellis S.G. Cox D.A. Hermiller J. O'Shaughnessy C. Mann J.T. Turco M. Caputo R. Bergin P. Greenberg J. Popma J.J. Russell M.E. A polymer-based, paclitaxel-eluting stent in patients with coronary artery disease.N Engl J Med. 2004; 350: 221-231Crossref PubMed Scopus (2659) Google Scholar In the pivotal DES trials (SIRIUS and TAXUS-IV), the lack of efficacy of DESs over BMSs with specific reference to large vessels was explained by the small cohort of patients available for the subset analysis. However, our study, with a larger cohort of patients, further supports the hypothesis that DESs do not have an edge over BMSs for larger vessels. It stands to reason that, given a similar degree of neointimal proliferation around a stent of any diameter, neointimal growth occurring in large vessels would be less likely to cause clinically or angiographically significant restenosis. With regard to BMSs, even a late loss of 1 mm (rarely seen with the new generations of BMSs) in a ≥3.5-mm vessel would render a 2.5-mm diameter vessel at long-term follow-up. This translates into binary restenosis of <50% and sufficient patency that neither compromises hemodynamics nor requires further intervention. This study has important implications. Although a wealth of data currently exist for patients with various clinical risk factors and coronary lesion subsets demonstrating relative superiority of DESs over BMSs for long-term restenosis, no study has demonstrated a mortality benefit of 1 approach over the other.7Roiron C. Sanchez P. Bouzamondo A. Lechat P. Montalescot G. Drug eluting stents: an updated meta-analysis of randomised controlled trials.Heart. 2006; 92: 641-649Crossref PubMed Scopus (191) Google Scholar, 8Babapulle M.N. Joseph L. Belisle P. Brophy J.M. Eisenberg M.J. A hierarchical Bayesian meta-analysis of randomised clinical trials of drug-eluting stents.Lancet. 2004; 364: 583-591Abstract Full Text Full Text PDF PubMed Scopus (613) Google Scholar In addition, Marzocchi et al11Marzocchi A. Piovaccari G. Manari A. Aurier E. Benassi A. Saia F. Casella G. Varani E. Santarelli A. Guastaroba P. Grilli R. Maresta A. Comparison of effectiveness of sirolimus-eluting stents versus bare metal stents for percutaneous coronary intervention in patients at high risk for coronary restenosis or clinical adverse events.Am J Cardiol. 2005; 95: 1409-1414Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar evaluated the effectiveness of sirolimus-eluting stents in a real-world scenario. At 9 months, they found similar rates of death and myocardial infarction, and the unadjusted major adverse cardiac event rate also showed no significant difference between the 2 groups (12.1% vs 12.3%, p = NS). Only in a prespecified high-risk population was there a significant difference in major adverse cardiac events. The difference was entirely driven by target vessel revascularization.11Marzocchi A. Piovaccari G. Manari A. Aurier E. Benassi A. Saia F. Casella G. Varani E. Santarelli A. Guastaroba P. Grilli R. Maresta A. Comparison of effectiveness of sirolimus-eluting stents versus bare metal stents for percutaneous coronary intervention in patients at high risk for coronary restenosis or clinical adverse events.Am J Cardiol. 2005; 95: 1409-1414Abstract Full Text Full Text PDF PubMed Scopus (36) Google Scholar Low-risk populations (i.e., those with large vessels) would not receive benefit from DESs. Further, widespread DES implantation is not without concerns. First, DES implantation, due to inhibition of wound healing by sirolimus or paclitaxel, mandates long-term dual platelet inhibition.12Joner M. Finn A.V. Farb A. Mont E.K. Kolodgie F.D. Ladich E. Kutys R. Skorija K. Gold H.K. Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk.J Am Coll Cardiol. 2006; 48: 193-202Abstract Full Text Full Text PDF PubMed Scopus (2514) Google Scholar Although it aids in decreasing in-stent restenosis and minimizing stent thrombosis, long-term thienopyridine administration exposes patients to risks of bleeding. Second, after thienopyridine discontinuation, patients are then exposed to risks of late restenosis and late stent thombosis.7Roiron C. Sanchez P. Bouzamondo A. Lechat P. Montalescot G. Drug eluting stents: an updated meta-analysis of randomised controlled trials.Heart. 2006; 92: 641-649Crossref PubMed Scopus (191) Google Scholar, 9Pfisterer M. Brunner-La Rocca H.P. Buser P.T. Rickenbacher P. Hunzker P. Mueller C. Jeger R. Bader F. Oswald C. Kaiser C. 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: 2584-2591Abstract Full Text Full Text PDF PubMed Scopus (1278) Google Scholar, 12Joner M. Finn A.V. Farb A. Mont E.K. Kolodgie F.D. Ladich E. Kutys R. Skorija K. Gold H.K. Virmani R. Pathology of drug-eluting stents in humans: delayed healing and late thrombotic risk.J Am Coll Cardiol. 2006; 48: 193-202Abstract Full Text Full Text PDF PubMed Scopus (2514) Google Scholar Third, the cost of DESs is significantly higher than that of BMSs, even after 6-month follow-up and inclusion of the cost borne by subsequent events.13Kaiser C. Brunner-La Rocca H.P. Buser P.T. Bonetti P.O. Osswald S. Linka A. Bernheim A. Zutter A. Zellweger M. Grize L. Pfisterer M.E. Incremental cost-effectiveness of drug-eluting stents compared with a third-generation bare-metal stent in a real-world setting: randomised Basel Stent Kosten Effektivitats Trial (BASKET).Lancet. 2005; 366: 921-929Abstract Full Text Full Text PDF PubMed Scopus (333) Google Scholar Based on these issues, it is desirable to identify populations in whom BMSs have equivalent efficacy to DESs. With target lesion revascularization rates of 3.5% at 1 year, patients with large coronary vessels represent such a population. Even after adjustment for diabetes and longer stents, no differences between BMSs and DESs emerged for the larger vessels. The present study is limited because of its retrospective nature and is therefore subject to the limitations pertinent to this type of clinical investigation. This study is not randomized and also lacks systematic angiographic follow-up and quantitative coronary analysis data. Although propensity scoring was used to match baseline characteristics of patients in each group, inherent biases in patient selection are possible. However, because of the low incidence of events in the study population, emergence of a significant difference between groups is unlikely.