Systematic literature review and expert meeting report on health-related quality of life in chronic venous disease.

INTRODUCTION: Chronic venous disease (CVD) can lead to considerable morbidity and impact health-related quality of life (HRQoL). The aim of this review was twofold: (i) to provide a deeper understanding of how CVD affects HRQoL (physical, psychological and social functioning), and (ii) to review the impact of evidence-based veno-active drugs (VADs) on HRQoL. EVIDENCE ACQUISITION: For the effect of CVD on HRQoL, information was gathered during an Expert Consensus Meeting, during which data were presented from both the patient and physician perspective assessed with validated quality-of-life measures. For the impact of VADs on HRQoL, a systematic literature review was performed using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Electronic databases were searched for real world evidence or randomized-controlled trials (RCT) vs. placebo, reporting data on the influence of VADs on HRQoL in patients with CVD. EVIDENCE SYNTHESIS: CVD can negatively affect daily life in a number of areas related to pain, physical function and social activities. The impact of CVD on HRQoL begins early in the disease and for patients the emotional burden of the disease is as high as the physical burden. In contrast, physicians tend to overestimate the physical impact. The database search yielded 184 unique records, of which 19 studies reporting on VADs and HRQoL in patients with CVD met the inclusion criteria (13 observational and 6 RCTs). Micronized purified flavonoid fraction (MPFF) was the most represented agent, associated with 12/19 studies (2 RCTs and 10 observational). Of the 6 RCTs, only MPFF, aminaphthone and low-dose diosmin provided statistically significant evidence for improvement on HRQoL compared with placebo; for the other VADs improvements in HRQoL were not statistically different from placebo. MPFF was also associated with improvements in HRQoL in the observational studies, across all CEAP clinical classes, as monotherapy or in combination with other conservative therapy, and for all aspects of HRQoL: physical, psychological, and social. Real-world data for the other VADs were scarce. Ruscus extract, sulodexide and a semi-synthetic diosmin were each represented by a single observational study and these limited data were associated with statistically significant improvements compared with baseline in overall and subdomain scores across the range of CEAP clinical classes. CONCLUSIONS: CVD can impair patients' HRQoL significantly at all stages of the disease. MPFF has the greatest evidence base of clinical use in both RCT and real-world observational studies for effectiveness on HRQoL and is recognized by international guidelines. The complete video presentation of the work is available online at www.minervamedica.it (Supplementary Digital Material 1: Supplementary Video 1, 5 min, 194 MB).

Efficacy and safety of Actovegin in the treatment of intermittent claudication: results of an international, multicenter, placebo-controlled, randomized, phase IIIb clinical trial (APOLLO).

BACKGROUND: This study aimed to assess the efficacy and safety of Actovegin for the treatment of patients with Fontaine stage IIB peripheral arterial disease (PAD). METHODS: The study included 366 patients with Fontaine stage IIB PAD from 19 centers (Russia, Georgia, Kazakhstan). Placebo or Actovegin (1200 mg daily [QD]) were administered intravenously for two weeks, followed by a 10-week course of oral administration (placebo or Actovegin 1200 mg QD). The primary efficacy outcome was percentage change in the initial claudication distance (ICD) by week 12. Secondary outcomes included percent and absolute changes in ICD, absolute claudication distance (ACD) and changes in Quality of Life (QoL) assessed by the SF-36 Mental Health Score. RESULTS: The increase in ICD after 12 weeks of Actovegin treatment was 29.19% (LS mean [Actovegin vs. placebo]; 95% CI: 9.35-49.02; P=0.0041). The percentage increase in ICD at 24 weeks was 35.51% (LS mean; 95% CI: 10.96-60.05; P=0.0047), which correspond to an increase in absolute ICD of 41.22 m (LS mean; 95% CI: 16.77-65.66; P=0.0010). The percentage increase in ACD after 24 weeks was 36.47% compared with the baseline (LS mean; 95% CI: 10.07-62.88; P=0.0069), which corresponded to an absolute increase in ACD of 50.92 m (LS mean; 95% CI: 18.35-83.49; P=0.0023). A statistically significant improvement in QoL with Actovegin compared with placebo was demonstrated within 24 weeks (LS mean 2.28; 95% CI: 0.88-3.68; P=0.0015). Actovegin demonstrated an acceptable safety and tolerability profile with minor differences from placebo. CONCLUSIONS: The results of this 12-week course of Actovegin demonstrated its superiority over placebo in the increase in ICD and ACD at weeks 2, 12 and 24 from the start of treatment. Actovegin has an acceptable safety and tolerability profile.