Vasoprotectives: Efficacy and safety of capillary stabilising agents for venous insufficiency or haemorrhoids

Fotolia_45417819_XS1
Research area: Health economics

Project leaders: Ingrid Zechmeister-Koss

Project team: Ingrid Zechmeister-Koss

Duration: May 2014 – December 2014
Publication: LBI-HTA Project report. 79:https://eprints.aihta.at/1047/

Language: English (with German summary and marginal notes)
Suggested by: Austrian Social Insurances/HVB

Background:
Vasoprotectives are blood vessels affecting drugs and constitute a therapeutic subgroup of the group “C-Cardiovascular System” in the Anatomical Therapeutic Chemical / Defined Daily Dose Classification (ATC-Code) with the code C05. The project will focus on the subcategory C05C “capillary stabilising agents”. These drugs are mainly used to treat venous insufficiency (particularly the symptoms) and haemorrhoids and are given oral as tablets. The products are often prescribed by physicians, whereas the benefit is not clear.

Aim of the project:
The aim of the project is to provide a systematic analysis of the literature on the effectiveness and safety of capillary stabilising agents (ATC-Code C05C) for the treatment of venous insufficiency and haemorrhoids.

Research questions:

  1. Are the capillary stabilising agents, listed in the Austrian reimbursement scheme for pharmaceuticals, more effective and safer for the treatment of patients with venous insufficiency and haemorrhoids with regard to defined outcomes (see PICO scheme) compared to other alternatives (no treatment, placebo, etc.)?
  2. Are there any differences between the different capillary stabilising agents according to effectiveness and safety?

Inclusion criteria (PICO):

Population

Patients with:

  • Venous insufficiency
  • Haemorrhoids

Intervention, Setting

Oral medication of capillary stabilising agents (ATC-Code C05C):

  • Oxerutin 0,3 (Venoruton 300 mg)
  • Oxerutin 0,5 (Venoruton 500 mg)
  • Oxerutin 1,0 (Venoruton 1000 mg)
  • Flavonoidfraktion 0,5 (Daflon 500 mg)
  • Aescin 0,02 (Reparil 20 mg)
  • Aescin 0,05 (Venosin retard 50 mg)
  • Calciumdobesilat 0,5 (Doxium 500 mg)

Control

Venous insufficiency:

  • No intervention,
  • Life style changes (exercising, diet, elevate legs, etc.),
  • Medical treatment (placebo, other capillary stabilising agents mentioned under “intervention”, antibiotics, etc.),
  • Local treatment (compressions, etc.; additional wound dressings and debridement if applicable),
  • Surgical interventions (vein stripping, superficial vein surgery, sclero-therapy, interruption of perforator veins, etc.).

Haemorrhoids:

  • No intervention,
  • Life style changes (diet, etc.),
  • Medical treatment (placebo, other capillary stabilising agents mentioned under “intervention”, etc.),
  • Local/Office-based treatment (Rubber Band Ligation, Sclero-Therapy, Infrared-Coagulation, etc.),
  • Surgical interventions (Surgical Excision, Stapled Haemorrhoidopexy, Doppler Guided Ligation, etc.).

Outcomes

Effectiveness:

  • Venous insufficiency:
  • Symptom improvement (pain, swellings, inflammations, etc.),
  • Long-term: improvement of wound healing, prevention of ulcers.
  • Haemorrhoids:
    • Symptom improvement (pain, itchiness, bleeding, etc.),
    • Improvement of long-term complications (incontinence, iron deficiency, etc.).

Safety:

  • Complications (gastrointestinal and neurovegetative disorders, allergic reactions, vomiting, nausea, headache, pain, dizziness, inflammation, tachycardia, etc.).

Types of studies

systematic reviews, meta-analyses, HTA reports, prospective controlled studies with ? 10 patients (for effectiveness and safety), prospective uncontrolled studies with ? 50 patients (for safety only)

Publication period

1900-2014

Language

German/ English

Type of publication

published journal articles and research reports

Exclusion criteria:
Population:

  • animals

Intervention:

  • Vasoprotectives with ATC-Code C05A “agents for treatment of haemorrhoids and anal fissures for topical use” and C05B “antivaricose therapy”.

Types of studies

  • editorials, letters to the editor, comments, other correspondence etc.
  • retrospective studies
  • case-reports
  • case-series
  • controlled studies with less than 10 patients
  • uncontrolled studies with less than 50 patients

Types of publications

  • unpublished documents
  • abstracts, posters, comments, letters
  • books

Methods:
Systematic Review based on published documents, and comparative effectiveness analysis if applicable:

  • Systematic literature search in:
    • Medline, Embase, The Cochrane Library, others
    • Handsearch in references (as appropriate via Scopus), internet- search
  • Data extraction: Two review authors include and exclude studies, independently from each other. One author extracts the data and a second author controls the extracted data.
  • Assessing risk of bias and strength of evidence: according to the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) approach.
  • Comparative effectiveness analysis: using methods guides (e.g. from the Agency for Healthcare Research and Quality, etc.)

Time schedule/ milestones:

Period

task

May 2014

scoping, precision of PICO-question

May - June 2014

systematic literature search, non-systematic hand search, literature selection

July - September 2014

data extraction, synthesis and assessing of evidence, drafting of report

September - October 2014

internal and external review, publication