Un apartado esencial del intervencionismo coronario percutáneo es la terapia anticoagulante. A pesar de la constante evolución de las técnicas percutáneas, la heparina no fraccionada continúa siendo la terapia más utilizada, debido fundamentalmente a la tradición y a la comodidad de su uso. Sin embargo, su utilización presenta inconvenientes, como la variabilidad en el efecto, la necesidad de controlarlo y la capacidad de activación de las plaquetas. Se dispone de otros fármacos que o bien han demostrado eficacia y seguridad o están en evaluación como alternativas a la heparina en el futuro. Nos referimos a las heparinas de bajo peso molecular, los inhibidores directos de la trombina y los pentasacáridos. En este capítulo se analizan los diferentes regímenes de anticoagulación con heparina no fraccionada, heparinas de bajo peso molecular y pentasacáridos. Los inhibidores directos de la trombina serán tratados en un capítulo posterior.
Palabras clave
Anticoagulantes
Angioplastia coronaria
Fármacos
Stent
Este artículo solo puede leerse en
pdf
Bibliografía
[1.]
J. Hirsh, T.E. Warkentin, S.G. Shaughnessy, S.S. Anand, J.L. Halperin, R. Raschke, et al.
Heparin and low-molecular-weight heparin: mechanisms of action, pharmacokinetics, dosing, monitoring, efficacy, and safety.
Chest, (2001), 119 pp. S64-S94
[2.]
G.C. Wong, R.P. Giugliano, E.M. Antman.
Use of low-molecularweight heparins in the management of acute coronary artery syndromes and percutaneous coronary intervention.
Jama, (2003), 289 pp. 331-342
[3.]
J.J. Ferguson, R.M. Califf, E.M. Antman, M. Cohen, C.L. Grines, S. Goodman, et al.
Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial.
Jama, (2004), 292 pp. 45-54
[4.]
A.M. Lincoff, J.A. Bittl, R.A. Harrington, F. Feit, N.S. Kleiman, J.D. Jackman, et al.
Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial.
Jama, (2003), 289 pp. 853-863
[5.]
S.R. Mehta, P.G. Steg, C.B. Granger, J.P. Bassand, D.P. Faxon, J.I. Weitz, et al.
Randomized, blinded trial comparing fondaparinux with unfractionated heparin in patients undergoing contemporary percutaneous coronary intervention: Arixtra Study in Percutaneous Coronary Intervention: a Randomized Evaluation (ASPIRE) Pilot Trial.
Circulation, (2005), 111 pp. 1390-1397
[6.]
B. Benito, M. Masotti, A. Betriu.
Avances en el tratamiento farmacológico coadyuvante en la intervención coronaria.
Rev Esp Cardiol, (2005), 58 pp. 729-743
[7.]
S. Kokolis, E. Cavusoglu, L.T. Clark, J.D. Marmur.
Anticoagulation strategies for patients undergoing percutaneous coronary intervention: unfractionated heparin, low-molecular-weight heparins, and direct thrombin inhibitors.
Prog Cardiovasc Dis, (2004), 46 pp. 506-523
[8.]
M. Cohen, C. Demers, E.P. Gurfinkel, A.G. Turpie, G.J. Fromell, S. Goodman, et al.
Low-molecular-weight heparins in non-ST-segment elevation ischemia: the ESSENCE trial. Efficacy and safety of subcutaneous enoxaparin versus intravenous unfractionated heparin, in non-Q-wave coronary events.
Am J Cardiol, (1998), 82 pp. L19-L24
[9.]
J.I. Weitz, M. Hudoba, D. Massel, J. Maraganore, J. Hirsh.
Clotbound thrombin is protected from inhibition by heparin-antithrombin III but is susceptible to inactivation by antithrombin IIIindependent inhibitors.
J Clin Invest, (1990), 86 pp. 385-391
[10.]
Novel dosing regimen of eptifibatide in planned coronary stent implantation (ESPRIT): a randomised, placebo-controlled trial. Lancet. 2000;356:2037-44.
[11.]
M. Cohen, C. Demers, E.P. Gurfinkel, A.G. Turpie, G.J. Fromell, S. Goodman, et al.
A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group.
N Engl J Med, (1997), 337 pp. 447-452
[12.]
T.A. Mabin, D.R. Holmes Jr, H.C. Smith, R.E. Vlietstra, A.A. Bove, G.S. Reeder, et al.
Intracoronary thrombus: role in coronary occlusion complicating percutaneous transluminal coronary angioplasty.
J Am Coll Cardiol, (1985), 5 pp. 198-202
[13.]
B.S. Bull, R.A. Korpman, W.M. Huse, B.D. Briggs.
Heparin therapy during extracorporeal circulation. I. Problems inherent in existing heparin protocols.
J Thorac Cardiovasc Surg, (1975), 69 pp. 674-684
[14.]
J.J. Ferguson, K.G. Dougherty, C.M. Gaos, H.S. Bush, K.C. Marsh, D.R. Leachman.
Relation between procedural activated coagulation time and outcome after percutaneous transluminal coronary angioplasty.
J Am Coll Cardiol, (1994), 23 pp. 1061-1065
[15.]
C.R. Narins, W.B. Hillegass Jr, C.L. Nelson, J.E. Tcheng, R.A. Harrington, H.R. Phillips, et al.
Relation between activated clotting time during angioplasty and abrupt closure.
Circulation, (1996), 93 pp. 667-671
[16.]
K.T. Koch, J.J. Piek, R.J. De Winter, G.K. David, K. Mulder, J.G. Tijssen, et al.
Safety of low dose heparin in elective coronary angioplasty.
Heart, (1997), 77 pp. 517-522
[17.]
D.P. Chew, D.L. Bhatt, A.M. Lincoff, D.J. Moliterno, S.J. Brener, K.E. Wolski, et al.
Defining the optimal activated clotting time during percutaneous coronary intervention: aggregate results from 6 randomized, controlled trials.
Circulation, (2001), 103 pp. 961-966
[18.]
S.C. Smith Jr, J.T. Dove, A.K. Jacobs, J.W. Kennedy, D. Kereiakes, M.J. Kern, et al.
ACC/AHA guidelines for percutaneous coronary intervention (revision of the 1993 PTCA guidelines)-executive summary: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee to revise the 1993 guidelines for percutaneous transluminal coronary angioplasty) endorsed by the Society for Cardiac Angiography and Interventions.
Circulation, (2001), 103 pp. 3019-3041
[19.]
S.G. Ellis, G.S. Roubin, J. Wilentz, J.S. Douglas Jr, S.B.III. King.
Effect of 18- to 24-hour heparin administration for prevention of restenosis after uncomplicated coronary angioplasty.
Am Heart J, (1989), 117 pp. 777-782
[20.]
H.Z. Friedman, D.R. Cragg, S.M. Glazier, V. Gangadharan, D.L. Marsalese, T.L. Schreiber, et al.
Randomized prospective evaluation of prolonged versus abbreviated intravenous heparin therapy after coronary angioplasty.
J Am Coll Cardiol, (1994), 24 pp. 1214-1219
[21.]
E.A. Johnson, T.B. Kirkwood, Y. Stirling, J.L. Pérez-Requejo, G.I. Ingram, D.R. Bangham, et al.
Four heparin preparations: anti-Xa potentiating effect of heparin after subcutaneous injection.
Thromb Haemost, (1976), 35 pp. 586-591
[22.]
L.O. Andersson, T.W. Barrowcliffe, E. Holmer, E.A. Johnson, G.E. Sims.
Anticoagulant properties of heparin fractionated by affinity chromatography on matrix-bound antithrombin iii and by gel filtration.
Thromb Res, (1976), 9 pp. 575-583
[23.]
B. Casu, P. Oreste, G. Torri, G. Zoppetti, J. Choay, J.C. Lormeau, et al.
The structure of heparin oligosaccharide fragments with high anti-(factor Xa) activity containing the minimal antithrombin III-binding sequence. Chemical and 13C nuclear-magnetic-resonance studies.
Biochem J, (1981), 197 pp. 599-609
[24.]
R.D. Rosenberg, R.E. Jordan, L.V. Favreau, L.H. Lam.
Highly active heparin species with multiple binding sites for antithrombin.
Biochem Biophys Res Com, (1979), 86 pp. 1319-1324
[25.]
A. Danielsson, E. Raub, U. Lindahl, I. Bjork.
Role of ternary complexes, in which heparin binds both antithrombin and proteinase, in the acceleration of the reactions between antithrombin and thrombin or factor Xa.
J Biol Chem, (1986), 261 pp. 15467-15473
[26.]
D.A. Hoppensteadt, W. Jeske, J. Fareed, E.W. Bermes Jr.
The role of tissue factor pathway inhibitor in the mediation of the antithrombotic actions of heparin and low-molecular-weight heparin.
Blood Coagul Fibrinolysis, (1995), 6 pp. S57-S64
[27.]
B. Lojewski, P. Bacher, O. Iqbal, J.M. Walenga, D. Hoppensteadt, F. Leya, et al.
Evaluation of hemostatic and fibrinolytic alterations associated with daily administration of low-molecular-weight heparin for a 12-week period.
Semin Thromb Hemost, (1995), 21 pp. 228-239
[28.]
E. Young, P. Wells, S. Holloway, J. Weitz, J. Hirsh.
Ex-vivo and in-vitro evidence that low molecular weight heparins exhibit less binding to plasma proteins than unfractionated heparin.
Thromb Haemost, (1994), 71 pp. 300-304
[29.]
E. Rocha, J.A. Paramo, J. Sarra.
Heparinas de bajo peso molecular.
Med Clin (Barc), (1993), 100 pp. 620-627
[30.]
T.E. Warkentin, M.N. Levine, J. Hirsh, P. Horsewood, R.S. Roberts, M. Gent, et al.
Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin.
N Engl J Med, (1995), 332 pp. 1330-1335
[31.]
W. Klein, A. Buchwald, S.E. Hillis, S. Monrad, G. Sanz, A.G. Turpie, et al.
Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC).
Circulation, (1997), 96 pp. 61-68
[32.]
Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J. 1999;20:1553-62.
[33.]
E.M. Antman, C.H. McCabe, E.P. Gurfinkel, A.G. Turpie, P.J. Bernink, D. Salein, et al.
Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial.
Circulation, (1999), 100 pp. 1593-1601
[34.]
K.R. Karsch, M.B. Preisack, R. Baildon, V. Eschenfelder, D. Foley, E.J. García, et al.
Low molecular weight heparin (reviparin) in percutaneous transluminal coronary angioplasty. Results of a randomized, double-blind, unfractionated heparin and placebo-controlled, multicenter trial (REDUCE trial). Reduction of restenosis after PTCA, early administration of reviparin in a double-blind unfractionated heparin and placebo-controlled evaluation.
J Am Coll Cardiol, (1996), 28 pp. 1437-1443
[35.]
M.M. Rabah, J. Premmereur, M. Graham, J. Fareed, D.A. Hoppensteadt, L.L. Grines, et al.
Usefulness of intravenous enoxaparin for percutaneous coronary intervention in stable angina pectoris.
Am J Cardiol, (1999), 84 pp. 1391-1395
[36.]
R. Choussat, G. Montalescot, J.P. Collet, E. Vicaut, A. Ankri, V. Gallois, et al.
A unique, low dose of intravenous enoxaparin in elective percutaneous coronary intervention.
J Am Coll Cardiol, (2002), 40 pp. 1943-1950
[37.]
Invasive compared with non-invasive treatment in unstable coronary-artery disease: FRISC II prospective randomised multicentre study.
FRagmin and Fast Revascularisation during InStability in Coronary artery disease Investigators.
Lancet, (1999), 354 pp. 708-715
[38.]
D.J. Kereiakes, N.S. Kleiman, E. Fry, G. Mwawasi, R. Lengerich, K. Maresh, et al.
Dalteparin in combination with abciximab during percutaneous coronary intervention.
Am Heart J, (2001), 141 pp. 348-352
[39.]
D.L. Bhatt, B.I. Lee, P.J. Casterella, M. Pulsipher, M. Rogers, M. Cohen, et al.
Safety of concomitant therapy with eptifibatide and enoxaparin in patients undergoing percutaneous coronary intervention: results of the coronary revascularization using integrilin and single bolus enoxaparin study.
J Am Coll Cardiol, (2003), 41 pp. 20-25
[40.]
M.A. Blazing, J.A. De Lemos, H.D. White, K.A. Fox, F.W. Verheugt, D. Ardissino, et al.
Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial.
JAMA, (2004), 292 pp. 55-64
[41.]
M.E. Bertrand, M.L. Simoons, K.A. Fox, L.C. Wallentin, C.W. Hamm, E. McFadden, et al.
Management of acute coronary syndromes: acute coronary syndromes without persistent ST segment elevation; recommendations of the Task Force of the European Society of Cardiology.
Eur Heart J, (2000), 21 pp. 1406-1432
[42.]
J.A. Cairns, P. Theroux, H.D. Lewis Jr, M. Ezekowitz, T.W. Meade.
Antithrombotic agents in coronary artery disease.
Chest, (2001), 119 pp. S228-S252
[43.]
E. Braunwald, E.M. Antman, J.W. Beasley, R.M. Califf, M.D. Cheitlin, J.S. Hochman, et al.
ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction: summary article. A report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina).
J Am Coll Cardiol, (2002), 40 pp. 1366-1374
[44.]
S. Silber, P. Albertsson, F.F. Aviles, P.G. Camici, A. Colombo, C. Hamm, et al.
Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology.
Eur Heart J, (2005), 26 pp. 804-847
[45.]
D.J. Kereiakes, G. Montalescot, E.M. Antman, M. Cohen, H. Darius, J.J. Ferguson, et al.
Low-molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention: an expert consensus.
Am Heart J, (2002), 144 pp. 615-624
[46.]
K.A. Bauer, D.W. Hawkins, P.C. Peters, M. Petitou, J.M. Herbert, C.A. Van Boeckel, et al.
Fondaparinux, a synthetic pentasaccharide: the first in a new class of antithrombotic agents: the selective factor Xa inhibitors.
Cardiovasc Drug Rev, (2002), 20 pp. 37-52
[47.]
K.A Bauer.
New pentasaccharides for prophylaxis of deep vein thrombosis: pharmacology.
Chest, (2003), 124 pp. S364-S370
[48.]
A.G. Turpie, A.S. Gallus, J.A. Hoek.
A synthetic pentasaccharide for the prevention of deep-vein thrombosis after total hip replacement.
N Engl J Med, (2001), 344 pp. 619-625
[49.]
P.K. Coussement, J.P. Bassand, C. Convens, M. Vrolix, J. Boland, G. Grollier, et al.
A synthetic factor-Xa inhibitor (ORG31540/ SR9017A) as an adjunct to fibrinolysis in acute myocardial infarction. The PENTALYSE study.
Eur Heart J, (2001), 22 pp. 1716-1724
[50.]
A. Vuillemenot, F. Schiele, N. Meneveau, S. Claudel, F. Donat, S. Fontecave, et al.
Efficacy of a synthetic pentasaccharide, a pure factor Xa inhibitor, as an antithrombotic agent: a pilot study in the setting of coronary angioplasty.
Thromb Haemost, (1999), 81 pp. 214-220
[51.]
M.L. Simoons, I.W. Bobbink, J. Boland, M. Gardien, P. Klootwijk, A.W. Lensing, et al.
A dose-finding study of fondaparinux in patients with non-ST-segment elevation acute coronary syndromes: the Pentasaccharide in Unstable Angina (PENTUA) Study.
J Am Coll Cardiol, (2004), 43 pp. 2183-2190
Copyright ©
2006. Sociedad Española de Cardiología