Vasoprotectives Efficacy and safety of capillary stabilising agents for venous insufficiency or haemorrhoidal diseases Final Report LBI-HTAProject Report No./Projektbericht Nr.: 79 ISSN: 1992-0488 ISSN-online: 1992-0496 Vasoprotectives Efficacy and safety of capillary stabilising agents for venous insufficiency or haemorrhoidal diseases Final Report Vienna, December 2014 Project Team/Projektteam Project Management/Projektleitung: Dr. rer. soc.oec. Ingrid Zechmeister-Koss Authors/AutorInnen: Dipl. Ges-oec. Stefan Fischer Dr. rer. soc.oec. Ingrid Zechmeister-Koss Additional contribution/Projektbeteiligung: Dr. Anna Glechner (Danube University Krems, performedmeta-analysis) Systematic Literature Search/Systematische Literatursuche: Tarquin Mittermayr, BA Hand Search/Handsuche: Stefan Fischer External Review/Externe Begutachtung: Priv.-Doz. Dr. med. univ. Thomas Gary (Klinische Abteilung für Angiologie, Meduni Graz) Dipl.-Ing. Erich Kvas (Hermesoft, Graz) Internal Review/Interne Begutachtung: Priv.-Doz. Dr. phil. Claudia Wild Correspondence/Korrespondenz: Stefan Fischer: [email protected] This report should be referenced as follows/Dieser Bericht soll folgendermaßen zitiert werden: Fischer S, Zechmeister-Koss I: Vasoprotectives: Efficacy and safety of capillary stabilising agents for venous insufficiency or haemorrhoidal diseases. LBI-HTA Project Report No.: 79, 2014, Vienna: Ludwig Boltzmann Institute for Health Technology Assessment. Conflict of Interest/Interessenskonflikt All authors declare no conflict of interest in sense of the Uniform Requirements of Manuscripts Statement of Medical Journal Editors (www.icmje.org)/Alle beteiligten AutorInnen erklären, dass keine Interessenskonflikte im Sinne der Uniform Requirements of Manuscripts Statement of Medical Journal Editors (www.icmje.org) bestehen. IMPRESSUM Media Owner and Publisher/Medieninhaber und Herausgeber: Ludwig Boltzmann Gesellschaft GmbH Nußdorferstr. 64, 6 Stock, A-1090 Wien http://www.lbg.ac.at/de/themen/impressum Responsible for Content/Für den Inhalt verantwortlich: Ludwig Boltzmann Institut/e for/für Health Technology Assessment (LBI-HTA) Garnisongasse 7/20, A-1090 Wien http://hta.lbg.ac.at/ Die HTA-Projektberichte erscheinen unregelmäßig und dienen der Veröffentlichung der Forschungsergebnisse des Ludwig Boltzmann Instituts für Health Technology Assessment. Die HTA-Projektberichte erscheinen in geringer Auflage im Druck und werden über den Dokumentenserver „http://eprints.hta.lbg.ac.at„ der Öffentlichkeit zur Verfügung gestellt: LBI-HTA Projektbericht Nr.: 79 ISSN:1992-0488 ISSN-online:1992-0496 © 2014 LBI-HTA – All rights reserved/Alle Rechte vorbehalten Content Summary ........................................................................................................................................................ 9 Zusammenfassung ...................................................................................................................................... 13 1 Background .................................................................................................................................................. 21 1.1 Targeted diseases ........................................................................................................................................ 21 1.1.1 Diseases of the veins ............................................................................................................................... 21 1.1.2 Venous insufficiency (chronic) ............................................................................................................. 22 1.1.3 Haemorrhoids ......................................................................................................................................... 24 1.2 Vasoprotectives: Capillary stabilising agents ........................................................................................... 26 1.2.1 Bioflavonoids ........................................................................................................................................... 28 1.2.2 Other capillary stabilising agents ......................................................................................................... 29 2 Methods ....................................................................................................................................................... 31 2.1 Research questions ..................................................................................................................................... 31 2.2 Inclusion criteria ........................................................................................................................................ 31 2.3 Exclusion criteria ........................................................................................................................................ 32 2.4 Literature search ......................................................................................................................................... 33 2.5 Literature selection .................................................................................................................................... 34 2.6 Data extraction and analysis ...................................................................................................................... 34 2.7 Patient-relevant outcomes.......................................................................................................................... 36 2.7.1 Chronic venous insufficiency ................................................................................................................ 36 2.7.2 Haemorrhoidal disease .......................................................................................................................... 37 2.7.3 Clinical relevance of outcome indicators ............................................................................................. 38 3 Results .......................................................................................................................................................... 41 3.1 Chronic venous insufficiency .................................................................................................................... 41 3.1.1 Oxerutin-containing agents ................................................................................................................... 41 3.1.2 Flavonoid fraction-containing agents .................................................................................................. 63 3.1.3 20 mg aescin-containing agents ............................................................................................................ 84 3.1.4 50 mg aescin-containing agents ............................................................................................................ 86 3.1.5 Calcium dobesilate-containing agents ................................................................................................. 96 3.1.6 Comparison between capillary stabilising agents............................................................................. 115 3.2 Treatment of haemorrhoidal diseases ..................................................................................................... 127 3.2.1 Oxerutin-containing agents ................................................................................................................. 127 3.2.2 Flavonoid fraction-containing agents ................................................................................................ 132 3.2.3 20 mg aescin-containing agents .......................................................................................................... 156 3.2.4 50 mg aescin-containing agents .......................................................................................................... 156 3.2.5 Calcium dobesilate-containing agents ............................................................................................... 156 3.2.6 Comparison between capillary stabilising agents............................................................................. 156 4 Summary and discussion .......................................................................................................................... 163 4.1 Strength of evidence and clinical relevance of outcomes ...................................................................... 163 4.2 Summary of evidence ............................................................................................................................... 165 4.3 Limitations ................................................................................................................................................ 169 5 Conclusion ................................................................................................................................................. 171 6 Literature ................................................................................................................................................... 173 7 Appendix ................................................................................................................................................... 177 LBI-HTA | 2014 3 Vasoprotectives Figures Figure 1.2-1: Development of prescriptions of and costs for capillary stabilising agents in Austria Reference: From data sent by the Main Association of Austrian Social Security Institutions ....... 27 Figure 2.5-1: Summary of the process used to identify and select