Heparin-coated Palmaz-Schatz stents in human coronary arteries. Early outcome of the Benestent-II Pilot Study.

BACKGROUND The purpose of the Benestent-II Pilot Study was to evaluate the safety of delaying and eliminating anticoagulant therapy in patients receiving a heparin-coated stent in conjunction with antiplatelet drugs. METHODS AND RESULTS The study consisted of three initial phases (I, II, III) during which resumption of heparin therapy after sheath removal was progressively deferred by 6, 12, and 36 hours. In phase IV, coumadin and heparin were replaced by 250 mg ticlopidine and 100 mg aspirin. Of the 207 patients with stable angina pectoris and a de novo lesion in whom heparin-coated stent implantation was attempted, implantation was successful in 202 patients (98%). Stent thrombosis did not occur during all four phases, and the overall clinical success rate at discharge was 99%. Bleeding complications requiring blood transfusion or surgery fell from 7.9% in phase I to 5.9%, 4%, and 0% in the three following phases. Hospital stay was 7.4, 6.1, 7.2, and 3.1 days for the consecutive phases. The restenosis rate for the combined four phases was 13% (15% in phase I, 20% in phase II, 11% in phase III, and 6% in phase IV). The overall rate of reintervention for the four phases was 8.9%. At 6 months, 84%, 75%, 94%, and 92% of the patients of phases I to IV, respectively, were event free. For the four phases, the event-free rate was 86%, which compares favorably with the rate observed in the Benestent-I study (80%; relative risk, 0.68 [0.45 to 1.04]). CONCLUSIONS The implantation of stents coated with polyamine and end-point-attached heparin in stable patients with one significant de novo coronary lesion is well tolerated, is associated with no (sub)acute stent thrombosis, and results in a favorable event-free survival after 6 months.

[1]  R. Rosenberg,et al.  Effect of heparin and heparin fractions on platelet aggregation. , 1980, The Journal of clinical investigation.

[2]  H. Miyama,et al.  A new antithrombogenic heparinized polymer. , 1977, Journal of biomedical materials research.

[3]  F. Neumann,et al.  Platelet activation and coronary stent implantation. Effect of antithrombotic therapy. , 1996, Circulation.

[4]  C Di Mario,et al.  Who was thrombogenic: the stent or the doctor? , 1995, Circulation.

[5]  D. Watts,et al.  Concise encyclopedia of medical and dental materials , 1993 .

[6]  R. Connolly,et al.  Modification of the thrombogenicity of a self-expanding vascular stent. , 1991, Journal of investigative surgery : the official journal of the Academy of Surgical Research.

[7]  W Rutsch,et al.  A comparison of balloon-expandable-stent implantation with balloon angioplasty in patients with coronary artery disease. Benestent Study Group. , 1994, The New England journal of medicine.

[8]  M. Morice,et al.  Intracoronary stenting without coumadin: one month results of a French multicenter study. , 1995, Catheterization and cardiovascular diagnosis.

[9]  P. Serruys,et al.  Influence of Coronary Vessel Size on Renarrowing Process and Late Angiographic Outcome After Successful Balloon Angioplast , 1994, Circulation.

[10]  R. Larsson,et al.  A new non-thrombogenic surface prepared by selective covalent binding of heparin via a modified reducing terminal residue. , 1983, Biomaterials, medical devices, and artificial organs.

[11]  M. Turina,et al.  Superior hemodynamics in left heart bypass without systemic heparinization. , 1990, European journal of cardio-thoracic surgery : official journal of the European Association for Cardio-thoracic Surgery.

[12]  D. Labarre,et al.  Properties of heparin--poly(methyl methacrylate) copolymers. II. , 1977, Journal of biomedical materials research.

[13]  M. Turina,et al.  Long Term Cardiopulmonary Bypass without Systemic Heparinization , 1990, The International journal of artificial organs.

[14]  M. Jozefowicz,et al.  Heparin-Containing and Heparin-Like Polymers , 1986 .

[15]  D. Lane,et al.  Heparin: Chemical and Biological Properties Clinical Applications , 1989 .

[16]  P D Verdouw,et al.  Reduction in thrombotic events with heparin-coated Palmaz-Schatz stents in normal porcine coronary arteries. , 1996, Circulation.

[17]  J M Robins,et al.  Estimation of a common effect parameter from sparse follow-up data. , 1985, Biometrics.

[18]  U Lindahl,et al.  Further characterization of the antithrombin-binding sequence in heparin. , 1982, Carbohydrate research.

[19]  W. Hass,et al.  Ticlopidine, Platelets and Vascular Disease , 2011, Springer New York.

[20]  Grode Ga,et al.  Nonthrombogenic materials via a simple coating process. , 1969 .

[21]  Louis E. Teichholz,et al.  Angiographie morphology and the pathogenesis of unstable angina pectoris , 1985 .

[22]  E. Chiellini,et al.  Polymers in Medicine , 1983 .

[23]  P. Serruys,et al.  Benestent II: back to the future. , 1994, Journal of interventional cardiology.

[24]  J. Hoak,et al.  Binding of human thrombin to cultured human endothelial cells. , 1979, The Journal of biological chemistry.

[25]  P. Serruys,et al.  Stenting of coronary arteries. Are we the sorcerer's apprentice? , 1989, European heart journal.

[26]  P. Barragan,et al.  Ticlopidine and subcutaneous heparin as an alternative regimen following coronary stenting. , 1994, Catheterization and cardiovascular diagnosis.

[27]  S. W. Kim,et al.  Heparinized polyurethanes: in vitro and in vivo studies. , 1985, Journal of biomedical materials research.

[28]  M. Turina,et al.  Cardiopulmonary bypass without systemic heparinization. Performance of heparin-coated oxygenators in comparison with classic membrane and bubble oxygenators. , 1989, The Journal of thoracic and cardiovascular surgery.

[29]  E. Simonson,et al.  The Electrocardiogram in Population Studies: A Classification System , 1960, Circulation.

[30]  O. Larm,et al.  A new method for covalent coupling of heparin and other glycosaminoglycans to substances containing primary amino groups. , 1983, Carbohydrate research.

[31]  P. Serruys,et al.  Quantitative Coronary Angiography in Clinical Practice , 1994, Developments in Cardiovascular Medicine.

[32]  M. Kern,et al.  Attenuation of hypertensive-induced pulsus alternans by nifedipine and nitroglycerin. , 1994, Catheterization and cardiovascular diagnosis.

[33]  J. Marcum,et al.  Heparinlike molecules with anticoagulant activity are synthesized by cultured endothelial cells. , 1985, Biochemical and biophysical research communications.

[34]  F. Church,et al.  Antithrombin: structure and function. , 1991, Seminars in hematology.

[35]  P Hall,et al.  Intracoronary stenting without anticoagulation accomplished with intravascular ultrasound guidance. , 1995, Circulation.

[36]  L. Hsu.  Principles of heparin-coating techniques , 1991 .

[37]  A. Hoffman,et al.  COVALENT BINDING OF BIOMOLECULES TO RADIATION‐GRAFTED HYDROGELS ON INERT POLYMER SURFACES , 1972, Transactions - American Society for Artificial Internal Organs.

[38]  B. Butler,et al.  Surface tension effects of heparin coating on arterial line filters , 1990, Perfusion.

[39]  S. Cooper,et al.  A canine ex vivo series shunt for evaluating thrombus deposition on polymer surfaces. , 1984, Journal of biomedical materials research.

[40]  A. Linker,et al.  Structure of the antithrombin-binding site in heparin. , 1979, Proceedings of the National Academy of Sciences of the United States of America.

[41]  R. Larsson,et al.  The Search for Thromboresistance Using Immobilized Heparin , 1987, Annals of the New York Academy of Sciences.