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Hamostaseologie 2013; 33(01): 43-50
DOI: 10.5482/HAMO-12-12-0024
Review
Schattauer GmbH

Pulmonary embolism hotline 2012

Recent and expected trialsLungenembolie-Hotline 2012Alte und neue Studien
S. Konstantinides
1   Center for Thrombosis and Haemostasis, Johannes Gutenberg University Medical Center, Mainz, Germany
,
M. Lankeit
1   Center for Thrombosis and Haemostasis, Johannes Gutenberg University Medical Center, Mainz, Germany
› Author Affiliations
Further Information

Publication History

received: 19 December 2012

accepted in revised form: 09 January 2013

Publication Date:
28 December 2017 (online)

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Summary

Management of acute pulmonary embolism (PE) has advanced considerably in the past year, and progress is expected to continue in 2013. To help determine the optimal management strategy for normotensive patients with intermediate-risk PE, the Pulmonary Embolism Thrombolysis (PEITHO) study completed enrolment of 1006 patients with evidence of right ventricular dysfunction (by echocardiography or computed tomography) plus a positive troponin test. Patients have been randomised to thrombolytic treatment with tenecteplase versus placebo, and the effects on clinical end points (death or haemodynamic collapse) assessed at 7 and 30 days. The results are expected in spring 2013; long-term follow-up is also being performed. The results of a randomised trial on ultrasound- enhanced low-dose catheter-delivered thrombolysis will also become available soon. While optimisation of treatment with vitamin K antagonists incorporating pharmacogenetic testing is still being pursued, new oral anticoagulants are entering the field of PE treatment and secondary prophylaxis. Following the successful use of rivaroxaban as single oral drug therapy in the EINSTEIN-PE trial, the approval of this drug has recently been extended to cover, apart from deep vein thrombosis, PE as well. The apixaban (AMPLIFY) and edoxaban (HOKUSAI) trials have finished recruitment of PE patients, and their results will become available shortly. In the meantime, the AMPLIFY-EXT trial showed that both the therapeutic (5 mg twice daily) and the prophylactic dose (2.5 mg twice daily) of apixaban are effective and safe for longterm secondary prophylaxis after PE. For the extended prophylaxis (after the reommended initial anticoagulation period) of the (few) patients who are unable to tolerate any form of anticoagulation, low-dose asprin may be a safe albeit moderately efficacious option, as indicated by two recent investigator-initiated trials with a total of 1224 patients.

Zusammenfassung

Die Therapie der akuten Lungenembolie (LE) befindet sich im Umbruch. Um die optimale Management-Strategie für normotensive LEPatienten mit erhöhtem (intermediärem) Risiko herauszufinden, hat die Pulmonary Embolism Thrombolysis (PEITHO)-Studie 1006 Patienten mit Nachweis einer rechtsventrikulären Dysfunktion (im EKG oder CT) und einem positiven Troponin-Test eingeschlossen. Evaluiert wird – nach 7 und 30 Tagen – der Einfluss einer frühen thrombolytischen Behandlung auf den klinischen Verlauf. Diese Ergebnisse werden im Frühjahr 2013 erwartet, während die Langzeit-Follow-up-Phase (2 Jahre) der Studie weiterläuft. Eine weitere randomisierte Studie zum Stellenwert der ultraschallverstärkten, niedrig dosierten, kathetergelieferten Thrombolyse ist ebenfalls abgeschlossen und soll 2013 vorgestellt werden. Während die Optimierung der Antikoagulation mit Vitamin- K-Antagonisten (VKA) mittels pharmakogenetischer Tests weiterverfolgt wird, dringen die neuen oralen Anti koagulanzien auch in die Therapie und Sekundärprophylaxe der venösen Thromboembolie Erfolg versprechend ein. Nach dem erfolgreichen Einsatz von Rivaroxaban als „single oral drug”- Strategie in der EINSTEIN-PE Studie, wurde diese Substanz 2012 auch für die LE (nach bereits erfolgter Zulassung für die tiefe Venenthrombose im Jahr 2011) zugelassen. Die entsprechenden Studien mit Apixaban (AMPLIFY) und Edoxaban (HOKUSAI) haben ihre Patientenrekrutierung abgeschlossen, so dass ihre Ergebnisse in Kürze zu erwarten sind. Inzwischen zeigte die AMPLIFY-EXT-Studie, dass Apixaban sowohl in der therapeutischen (5 mg 2-mal täglich) als auch in der prophylaktischen (2,5 mg 2-mal täglich) Dosis für die Langzeitprophylaxe von LE - Rezidiven effektiv und sicher eingesetzt war-den kann. Für diese Spätphase (d.h. nach erfolgter 3- bis 6-monatiger Antikoagulation wie in den Leitlinien empfohlen) erscheint es auch möglich, Patienten, die keinerlei Anti - koagulanzien (weder VKA noch neue orale Faktor-Xa-Inhibitoren) tolerieren, mit niedrig dosierter (100 mg täglich) Azetylsalizylsäure (ASS) prophylaktisch zu behandeln. Zwei kürzlich publizierte, nicht durch die Industrie gesponserte randomisierte Studien mit insgesamt 1224 Patienten zeigten, dass ASS in diesem Zusammenhang eine mäßig effektive aber sichere Prophylaxe von venösen (und arteriellen) Thrombosen leisten kann.

Keywords

Pulmonary embolism - therapy - thrombolysis - anticoagulation - new oral anticoagulants - trials

Schlüsselwörter

Lungenembolie - Therapie - Thrombolyse - Antikoagulation - neue orale Antikoagulanzien - Studien
 

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