Update on Direct Oral AntiCoagulants (DOACs)

Jürgen Koscielny; Christoph Rosenthal; Christian von Heymann

doi:10.5482/HAMO-16-10-0041

Hämostaseologie, Table of Contents

Hamostaseologie 2017; 37(04): 267-275
DOI: 10.5482/HAMO-16-10-0041

Review

Schattauer GmbH

Update on Direct Oral AntiCoagulants (DOACs)

Perioperative “switching”, drug interactions and persistenceUpdate Direkte Orale AntiKoagulanzien (DOAKs)Perioperatives „Switching”, Medikamenteninteraktionen und Persistenz

Authors

Jürgen Koscielny

¹Gerinnungsambulanz mit Hämophiliezentrum im ambulanten Gesundheitszentrum (AGZ), Charité Campus Mitte (CCM), Universitätsmedizin Berlin
Christoph Rosenthal

²Klinik für Anästhesiologie mit Schwerpunkt operative Intensivmedizin, Charité Campus Virchow Klinikum (CVK), Universitätsmedizin Berlin
Christian von Heymann

³Klinik für Anästhesie, Intensivmedizin, Notfallmedizin und Schmerztherapie, Vivantes Klinikum im Friedrichshain, Berlin

Abstract

Summary

Recent findings require an update of previous recommendations for the perioperative use of Direct Oral AntiCoagulants (DOACs). A break in preoperative treatment of 24–96 hours is recommended based on the pharmacokinetic profiles of DOACs and depends on individual patient characteristics, their renal and possibly liver function, and their surgery-related risk of bleeding. In cases of renal or hepatic insufficiency, whether to extend the preoperative interruption of IIa- and Xa-inhibitors is a clinical decision that must be reached on an individual patient basis. In cases of epidural or spinal anaesthesia, more conservative pausing-intervals are recommended due to the risk of persistent neurologic deficits (e.g., paraplegia) following the development of spinal subdural and epidural haematomas. Elective surgery should be postponed according to these recommendations. Preoperative “bridging” with LMWH (more precisely referred to as „switching”) should be omitted due to a significantly increased risk of bleeding. In addition, the incidence of perioperative thromboembolic risks, such as DVT, PE, and stroke, are no different whether interruption or “switching” is undertaken. Postoperatively, the DOACs can be reinstituted within the first 24 hours. In cases of major surgery or if there is a higher risk of bleeding, resumption of DOACS should only begin after 24–72 hours. In patients with an elevated thromboembolic risk, transient postoperative LMWH administration can be recommended during this period.

Interaction of DOACs with other drugs usually occurs during the absorption, transport and elimination of these drugs. Therefore, substance- specific restrictions and recommendations should be observed during these times. In everyday clinical practice, webbased, independent information portals on drug-interactions are very helpful in providing safe and rapid information about potential interactions when DOACs are used in combination with other drugs, especially during perioperative management.

Non-adherence to medications is a worldwide problem that has dangerous and costly consequences. Present data suggest that persistence is the primary factor that supports adherence. Despite the adherence data presented in the DOACS approval studies (e.g., persistence in the treatment of acute venous thromboembolism has been reported to be between 94–99%), the first registries and meta-analyses provide sobering results regarding the incidence of persistence and the success rate of interventions designed to improve adherence with DOACs in cases of long-term usage.

Zusammenfassung

Aktuelle Erkenntnisse erfordern die Aktualisierung früherer Empfehlungen zum perioperativen Einsatz von direkte orale Antikoagulanzien (DOAKs). Auf Grundlage der pharmakokinetischen Profile wird in Abhängigkeit von Nierenfunktion, ggf. Leberfunktion sowie individuellem und eingriffsspezifischem Blutungsrisiko eine präoperative Pausierung von 24–96 Stunden in Abhängigkeit von dem verwendeten DOAK empfohlen. Bei schwerer Nieren- oder Leberinsuffizienz ist es eine individuelle, klinische Entscheidung, die präoperative Pause für die Xa-inhibitoren zu verlängern. Für Patienten mit rückenmarksnahen Regionalanästhesieverfahren gelten aufgrund des Risikos von spinal sub- und epiduralen Hämatomen und dem Risiko bleibender schwerer neurologischer Defizite (Querschnittslähmung) sehr konservative Intervalle im oberen Pausierungsbereich. Ein bereits präoperativ beginnendes „Bridging” mit NMH (eigentlich „Switching”) sollte wegen signifikant erhöhter Blutungsrisiken unterbleiben. Das perioperative Thromboembolierisiko (z.B. Thrombose, Lungenembolie, Hirninfarkt) ist nach einer präoperativen Pause bzw. einem präoperativen „Switching” nicht unterschiedlich. Postoperativ können DOAKs innerhalb von 24 h, nach größeren Eingriffen bzw. höherem Blutungsrisiko erst nach 24–72 Stunden wiederaufgenommen werden. Eine postoperative, passagere Umstellung auf eine NMH-Gabe („Switching”) bei erhöhtem venösem Thromboembolierisiko kann in diesem Zeitraum erfolgen.

Medikamenteninteraktionen von direkten oralen Antikoagulanzien treten meist bei der Absorption, beim Transport und bei der Elimination von anderen Medikamenten auf. Hierbei sind substanzspezifische Einschränkungen und Empfehlungen zu beachten. Um im klinischen Alltag eine sichere und schnelle Information, auch über DOAKs in Kombination mit anderen Medikamenten im perioperativen Management, zu erhalten, sind webbasierte, unabhängige Informationsportale sehr hilfreich.

Die Non-Adhärenz von Medikamenten ist weltweit verbreitet, ist gefährlich und teuer in ihren Folgen. Die aktuellen Daten beschreiben vorwiegend die Persistenz als ein orientierendes Maß für die Adhärenz. Unabhängig von den Zulassungsstudien der DOAKs (Persistenz bei der Therapie akuter venöser Thromboembolien zwischen 94 – 99%) liefern erste Register und Metaanalysen ernüchternde Ergebnisse zur Persistenz und zur Verbesserung der Adhärenz der DOAKs in der Langzeitanwendung.

Keywords

DOACs - rivaroxaban - apixaban - edoxaban - dabigatran - “switching” - drug interactions - persistence

Schlüsselwörter

DOAKs - Rivaroxaban - Apixaban - Edoxaban - Dabigatran - „Switching” - Medikamenteninteraktionen - Persistenz

Full Text

References

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