Stellenwert von Thrombozyten-Aggregationshemmern in der Sekundärprävention des ischämischen Schlaganfalls

Zusammenfassung

Einleitung: Das Ziel der Sekundärprophylaxe nach zerebraler Ischämie ist eine langfristige Hemmung der Thrombogenese um Rezidivereignisse zu verhindern. Thrombozytenaggregationshemmer (TAH) leisten laut Metaanalysen einen erheblichen Beitrag zur Reduktion des Rezidivrisikos nach TIA oder Schlaganfall mit einer relativen Risikoreduktion (RRR) von ca. 22 %. Das Ziel dieser Übersicht ist es, eine Zusammenfassung und kritische Reflektion der relevanten Studien und Metaanalysen zur Sekundärprophylaxe nach Schlaganfall sowie eine gezielte differenzialtherapeutische Empfehlung zu geben. Methoden: Grundlage der Arbeit ist die ausführliche Sichtung der Literatur zu TAH in der Sekundärprophylaxe nach zerebraler Ischämie vor allem der letzten 10 Jahre. Neben den klassischen Metaanalysen der Antiplatelet Trialists, werden die relevanten Einzelstudien (u. a. CATS, TASS, ESPS 2, CURE, CAPRIE) sowie Metaanalysen und post hoc Analysen zu diesen Studien referiert und interpretiert. Die Therapieempfehlungen orientieren sich an den Empfehlungen und Leitlinien nationaler (DGN), europäischer (EUSI) und internationaler (AHA/ASA) Fachgesellschaften. Die aktuelle Literatur zu Nebenwirkungen und pharmakologischen Interaktionen ist in die Übersicht inkorporiert worden. Schlussfolgerungen: ASS führt nach TIA oder Schlaganfall zu einer leichten Senkung des Rezidivrisikos von ca. 13 % und ist in niedrigen Dosen (50 - 325 mg/Tag) bei gleicher Effektivität besser verträglich. Ticlopidin ist aufgrund des Nebenwirkungsspektrums (Neutropenie, TTP) ein Reservemedikament. Clopidogrel ist bei vaskulären Patienten in der Sekundärprävention vaskulärer Ereignisse (Schlaganfall, Herzinfarkt, Tod vaskulärer Ursache) besser als ASS (RRR 8,7 %). Dieser Effekt ist v. a. bei kardiovaskulären Hoch-Risiko-Patienten deutlicher ausgeprägt. Dipyridamol+ASS ist bei Patienten mit TIA/Schlaganfall besser in der Sekundärprävention erneuter Schlaganfälle (RRR ca. 23 %) als ASS (im indirekten Vergleich auch als Clopidogrel), nicht aber peripher- und kardiovaskulärer Rezidivereignisse. Demnach sollte primär Clopidogrel bei Patienten mit kardiovaskulären Risikofaktoren oder ASS-Unverträglichkeit und primär Dipyridamol/ASS bei TIA/Schlaganfallpatienten mit niedriger kardiovaskulärer Komorbidität verschrieben werden. Studien zur Kombination von Clopidogrel/ASS (MATCH, CHARISMA) sowie zum Vergleich der Kombinationen (PRoFESS) stehen aus. Die Kombination Clopidogrel/ASS sollte derzeit im zerebrovaskulären Bereich nur im Rahmen von Studienprotokollen oder eines individuellen Heilversuches gegeben werden.

Abstract

Introduction: The goal of secondary prophylaxis following cerebral ischemia is a long lasting inhibition of thrombogenesis to prevent recurrent stroke or other vascular events. Platelet inhibitors (PI) according to meta-analyses lead to a relative risk reduction (RRR) of 22 % for vascular events after stroke. The aim of this article is a summary and critical review of all relevant studies and meta-analyses for secondary prevention of stroke and to give a differentiated therapeutic recommendation. Methods: We performed a careful and extensive review of the present literature for PI in the secondary prevention of stroke. Next to the classic meta-analyses such as the Antiplatelet Trialists' analysis, the relevant single trials (e. g. CATS, TASS, ESPS 2, CURE, CAPRIE) as well as meta-analyses and post hoc analyses of these studies are summarized and interpreted. Therapeutic recommendations are in consistence with the recommendations and guidelines of national (DGN), European (EUSI) and international (AHA/ASA) Groups/Associations. Also, the present literature was searched for new information with regard to side effects and pharmacological interactions and introduced into the review. Conclusions: ASA reduces the RR after TIA/stroke by ≈13 % and has the same efficacy with less side effects in lower dosages (50 - 325 mg/Tag). Ticlopidine is a reserve drug due to its unfavorable side effect profile (neutropenia, TTP). Clopidogrel is better than ASA (RRR 8.7 %) for vascular patients in preventing another vascular event (stroke, MI, vascular death). This effect is pronounced in patients at high risk for atherothrombotic events such as previous MI, cardiac surgery, or diabetes. Dipyridamole+ASA is better than ASA in patients with TIA/stroke (in indirect comparison also than Clopidogrel) for the secondary prevention of recurrent stroke (RRR 23 %), but not for the prevention of other vascular events. Therefore, Clopidogrel should be primarily given to patients with a high vascular risk (one or more cardiovascular risk factors) or to patients with ASA intolerance. Dipyridamole/ASA should be primarily given to TIA/stroke patients with a lower cardiovascular comorbidity. Studies for the combination of Clopidogrel/ASA (MATCH, CHARISMA) and for the comparison of both combinations (PRoFESS) are underway. At present, the combination of clopidogrel and ASA for cerebrovascular prevention should only be given within controlled studies or as an individual treatment with an accordingly acquired informed consent.

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