Zusammenfassung
Die duale antiaggregatorische Therapie mit Aspirin und Clopidogrel nach koronarer
Stentimplantation ist heute trotz fehlender offizieller Zulassung Standard der perinterventionellen
Behandlung. Die Clopidogrel-Therapie wird vor PCI mit einer „loading dose” begonnen.
Diese beträgt 300 mg mindestens 6 Stunden vor PCI, ansonsten 600 mg. Die notwendige
Dauer der dualen antiaggregatorischen Therapie nach koronarer Stentimplantation ist
von der Art des Stents und dem bestehenden Krankheitsbild abhängig und beträgt mindestens: 3 - 4 Wochen bei Bare-metal Stent, 6 Monate bei Drug-eluting Stent, 12 Monate nach
koronarer Brachytherapie und 9 Monate nach Akutem Koronarsyndrom. Diese Zeitintervalle
sollten auch bei bevorstehenden chirurgischen Eingriffen eingehalten werden. Vorzeitige,
nicht aufschiebbare Operationen müssen nach individueller Einschätzung des Blutungsrisikos
unter der antiaggregatorischen Therapie durchgeführt werden. Ein vorzeitiges Beenden
der antiaggregatorischen Therapie geht mit einem gesteigertem Risiko kardiovaskulärer
Ereignisse, insbesondere von Stenthrombose und Myokardinfarkten, einher. Von einer
prolongierten dualen antiaggregatorischen Therapie profitieren insbesondere kardiovaskuläre
Hochrisikopatienten. Patienten mit einer Indikation zur dauerhaften Antikoagulation
bedürfen nach koronarer Stentimplantation für den Zeitraum der größten Gefährdung
durch eine Stentthrombose einer kombinierten Gabe von Aspirin, Clopidogrel und Antikoagulantien
mit einem INR-Zielwert im unteren therapeutischen Bereich. Das erhöhte Risiko für
relevante Blutungen muss einkalkuliert und in Relation zum potenziellen Nutzen abgewogen
werden.
Summary
Dual antiplatelet-aggregation treatment with aspirin and clopidogrel after coronary
stent implantation is nowadays standard peri-interventional practice, although its
use is not yet licensed for this indication in many European countries. Clopidogrel
administration is initiated before PCI with a loading dose of 300 mg when given at
least 6 hours before PCI, otherwise 600 mg. The required duration of combined (aspirin
+ clopidogrel) antiplatelet-aggregation treatment after coronary stent implantation
depends on the type of stent and the pre-existing disease. After bare-metal stent
implantation dual antiplatelet medication is needed for at least 3-4 weeks, after
drug-eluting stent implantation 6 months, after coronary brachytherapy 12 months,
and 9 months after an acute coronary syndrome. These time intervals should also be
respected before any elective surgical intervention. Early operations, because postponement
is impossible, should be performed under antiplatelet-aggregation treatment after
assessment of bleeding risk in the individual case. Premature termination of this
treatment carries an increased risk of serious cardiovascular events, especially stent
thrombosis and myocardial infarction. Prolonged antiplatelet-aggregation treatment
is of benefit especially in patients with a high risk of serious cardiovascular events.
Patients with an indication for long-term anticoagulation may require, during the
period of highest risk of stent thrombosis after stent implantation, administration
of combined aspirin, clopidogrel and anticoagulants with an INR target value in the
lower therapeutic range. The increased risk of bleeding must be weighed up against
the potential benefit.
Literatur
1
ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac
surgery.
Circulation.
2002;
105
1257-1267
2
Batchalor W B, Mahaffay K W, Berger P B. et al .
A randomised, plazebo-controlled trial of enoxiparin after high-risk coronary stenting:
the ATLAST trial.
J Am Coll Cardiol.
2001;
38
1608-1613
3
Bertrand M B, Legrand V, Boland J. et al .
Randomized multicenter comparison of conventional anticoagulation versus antiplatelet
therapy in unplanned and elective coronary stenting. The Full Anticoagulation Versus
Asprin and Ticlopidin (FANTASTIC) Study.
Circulation.
1996;
98
1597-1603
4
Bertrand M E, Rupprecht H J, Urban P. et al. for the CLASSICS Investigators .
Double-blind study of the safety of clopidogrel with and without a loading dose in
combination with aspirin compared with ticlopidine in combination with aspirin after
coronary stenting: The Clopidogrel Aspirin Stent International Cooperative Study (CLASSICS).
Circulation.
2000;
102
624-629
5
Burger W, Chemnitius J M, Kneissl G D. et al .
Low-dose aspirin for secondary cardiovascular risks after its perioperative withdrawal
versus bleeding risks with its continuation-rewiev and meta-analysis.
J Inten Med.
2005;
257
399-414
6
Cleland J G, Findlay I, Jafri S. et al .
The Warfarin/Aspirin Study in Heart Failure (WASH): a randomized trial comparing antithrobotic
strategies for patients with heart failure.
Am Heart J.
2004;
148
157-164
7
Cremers B, Maack C, Böhm M.
Präoperative kardiovaskuläre Risikoeinschätzung - Therapie.
Dtsch Med Wochenschr.
2004;
129
1260-1264
8
Douketis J D, Johnson J A, Turpie A G.
Low-molecular-weight heparin as bridging anticoagulation during interruption of warfarin:
Assesment of a standardized periprocedural anticoagulation regimen.
Arch Intern Med.
2004;
164
1319-1326
9
Fox K AA, Mehta S R, Peters R. et al .
Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing
surgical revascularization for non-ST-Elevation acute coronary syndrome: The Clopidogrel
in Unstable angina to prevent Recurrent ischemic Events (CURE) Trial.
Circulation.
2004;
110
1202-1208
10 Gawaz M. Das Blutplättchen: Physiologie, Pathophysiologie, Membranrezeptoren, antithrombozytäre
Wirkstoffe und antithrombozytäre Therapie bei koronarer Herzerkrankung. 1. Auflage
Georg Thieme Verlag 1999: 54-63
11
Iakovou I, Schmidt T, Bonizzoni E. et al .
Incidence, predictors, and outcome of thrombosis after succesful implantation of drug-eluting
stents.
JAMA.
2005;
293
2126-2130
12
Hamm C W, Arntz H R, Bode C. et al .
Leitlinien: Akutes Koronarsyndrom (ACS) Teil 1: Akutes Koronarsyndrom ohne persistierende
ST-Hebung.
Z Kardiol.
2004;
93
72-90
13
Kaluza G L, Joseph J, Lee J R. et al .
Catastrophic outcomes of noncardiac surgery soon after coronary stenting.
J Am Coll Cardiol.
2000;
36
2351-2352
14
Leon M B, Baim D S, Popma J J. et al .
The stent anticoagulation restenosis study investigators. A clinical trial comparing
three antithrombotic-drug regimes after coronary-artery stenting.
N Engl J Med.
1998;
339
1665-1671
15
Lorenzoni R, Lazzerini G, Cocci F. et al .
Short-term prevention of thromboembolic complications in patients with atrial fibrillation
with aspirin plus clopidogrel: the Clopidogrel-Asprin Atrial Fibrillation (CLAAF)
pilot study.
Am Heart J.
2004;
148
e6
16
Marcucci C, Chassot P G.
Fatal myocardial infarction after lung resection in a patient with prophylactic preoperative
coronary stenting.
Br J Anaesth.
2004;
5
743-747
17
Massel D, Little S H.
Risks and benefits of adding anti-platelet therapy to warfarin among patients with
prosthetic heart valves: a meta-analysis.
J Am Coll Cardiol.
2001;
37
569-578
18
Mehta S R, Yusuf F, Peters R J. et al .
Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy
in patients undergoing percutaneous coronary intervention: the PCI-CURE study.
Lancet.
2001;
358
527-533
19
Moore M, Power M.
Perioperative hemorrhage and combined clopidogrel and aspirin therapy.
Anesthesiology.
2004;
101
792-794
20
Orford J L, Fasseas P, Melby S. et al .
Safety and efficacy of aspirin, clopidogrel, and warfarin after coronary stent placement
in patients with an indication for anticoagulation.
Am Heart J.
2004;
147
463-467
21
Patti G, Colonna G, Pasceri V. et al .
Randomized trial of high loading dose clopidogrel for reduction of periprocedural
myocardial infarction in patients undergoing coronary intervention.
Circulation.
2005;
111: 2099-2106
22
Rubboli A, Colleta M, Sangiorgio P. et al .
Antithrombotic strategies in patients with an indication for long term anticoagulation
undergoing coronary artery stenting: safety and efficacy data from a single center.
Ital Heart J.
2004;
5
919-925
23
Schömig A, Neumann F J, Kastrati A. et al .
A randomized comparison of antiplatelet and anticoagulant therapy after the placement
of coronary-artery stents.
N Engl J Med.
1996;
334
1084-1089
24
Sheldrake J.
Drug eluting stent penetration in Europe.
Cardiovasculare News.
2004;
9
20
25
Silber S, Albertsson P, Aviles FF.
for the task Force of PCI of the European Society of Cardiology Guidelines for percutaneous
coronary interventions.
Eur Heart J.
2005;
138
804-847
26
Spencer A, Becker C.
When guidelines collide… .
Am Heart J.
2004;
147
395-597
27
Steinhubl S R, Berger P B, Mann J T. et al .
Early and Sustained Dual Oral Antiplatelet Therapy Following Percutaneous Coronary
Intervention (CREDO).
JAMA.
2002;
288
2411-2420
28
Urban P, Macaya C, Rupprecht H J. et al .
Randomized evaluation of anticoagulation versus antiplatelet therapy after coronary
stent implantation in high-risk patients. The Multicenter Aspirin and Ticlopidin Trial
after Intracoronary Stenting (MATTIS).
Circulation.
1998;
98
2126-2132
29
Van Buren F, Mannebach H, Horstkotte D.
20. Bericht über die Leistungszahlen der Herzkatheterlabore in der Bundesrepublik
Deutschland.
Z Kardiol.
2005;
942
212-215
30
Wilson S H, Fasseas P, Orford J L. et al .
Clinical outcome of patients undergoing non-cardiac surgery in the two months following
coronary stenting.
J Am Coll Cardiol.
2004;
18
713-714
31
Yusuf S, Zhao F, Mehta S R. et al .
The Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) trial programme:
Effects of clopidogrel in addition of aspirin in patients with acute coronary sndromes
without ST-elevation.
N Engl J Med.
2001;
345
494-502
Prof. C. A. Nienaber
Universität Rostock, Klinik und Poliklinik für Innere Medizin, Abteilung Kardiologie
PF 100 888
18055 Rostock
Phone: 0381/494/7701
Fax: 0381/494/7703
Email: christoph.nienaber@med.uni-rostock.de