Kakkos SK, Nicolaides AN, et al.
International angiology : a journal of the International Union of Angiology. Date of publication 2018 Apr 1;volume 37(2):143-154.
1. Int Angiol. 2018 Apr;37(2):143-154. doi: 10.23736/S0392-9590.18.03975-5. Epub
2018 Jan 31.
Efficacy of micronized purified flavonoid fraction (Daflon®) on improving
individual symptoms, signs and quality of life in patients with chronic venous
disease: a systematic review and meta-analysis of randomized double-blind
placebo-controlled trials.
Kakkos SK(1), Nicolaides AN(2)(3).
Author information:
(1)Department of Vascular Surgery, University Hospital of Patras, Greece -
kakkos@upatras.gr.
(2)Imperial College London, London, UK.
(3)University of Nicosia Medical School, Nicosia, Cyprus.
INTRODUCTION: The use of a venoactive drug is considered an important component
of medical treatment of chronic venous disease (CVD), although the efficacy of
certain venoactive drugs (VADs) on one or more individual leg symptoms or signs
may have not been extensively studied to justify a strong recommendation in
guidelines on CVD. The aim of this systematic review and meta-analysis was to
study the effectiveness of the micronized purified flavonoid fraction (MPFF,
Daflon®) across the spectrum of defined venous symptoms, signs, quality of life
(QoL) and treatment assessment by the physician.
EVIDENCE ACQUISITION: On September 9, 2017, a systematic review of the databases
MEDLINE, Scopus and Cochrane Central was performed, supplemented by hand
searching, to identify randomized double-blind placebo-controlled trials on MPFF
in patients with CVD.
EVIDENCE SYNTHESIS: The main outcome measures were the individual and global
symptoms, leg edema and redness, skin changes, QoL and evaluation of the overall
effectiveness of the treatment by the physician. The effectiveness of MPFF
compared with placebo was expressed as risk ratio (RR) or standardized mean
difference (SMD) with 95% confidence interval (CI). Trial quality of evidence
was graded using the GRADE system.
RESULTS: We identified 7 trials, mostly with low risk of bias, involving 1,692
patients. On qualitative analysis, MPFF significantly improved nine defined leg
symptoms, including pain, heaviness, feeling of swelling, cramps, paresthesia,
burning sensation, and pruritus (itching), but also functional discomfort
compared with placebo, leg redness, skin changes and QoL. On quantitative
analysis, MPFF compared with placebo, assessed as a categorical variable,
reduced leg pain (RR 0.53, P=0.0001, NNT=4.2), heaviness (RR 0.35, P<0.00001,
NNT=2.0), feeling of swelling (RR 0.39, P<0.00001, NNT=3.1), cramps (RR 0.51,
P=0.02, NNT=4.8), paresthesia (RR 0.45, P=0.03, NNT=3.5), and functional
discomfort (RR 0.41, P=0.0004, NNT=3.0). Similarly, MPFF compared with placebo,
assessed as a continuous variable reduced pain (SMD -0.25, 95% CI -0.38 to
-0.11), heaviness (SMD -0.80, 95% CI -1.05 to -0.54), feeling of swelling (SMD
-0.99, 95% CI -1.25 to -0.73), burning sensation (SMD -0.46, 95% CI -0.78 to
-0.14), cramps (SMD -0.46, 95% CI -0.78 to -0.14), and functional discomfort
(SMD -0.87, 95% CI -1.13 to -0.61). Regarding objective assessments of leg
edema, the use of MPFF compared with placebo reduced ankle circumference (SMD
-0.59, 95% CI -1.15 to -0.02), and leg redness (SMD -0.32, 95% CI -0.56 to
-0.07, RR 0.50, P=0.03, NNT=3.6), improved skin changes (RR 0.18, P=0.0003,
NNT=1.6) and quality of life (SMD -0.21, 95% CI -0.37 to -0.04) and was
associated with clinical improvement as assessed by the physician (RR 0.28,
P<0.00001, NNT=2.5). Heterogeneity was mostly minimal. The existing evidence
where sufficient was mostly of high quality.
CONCLUSIONS: Based on high quality evidence, MPFF is highly effective in
improving leg symptoms, edema and quality of life in patients with CVD.
DOI: 10.23736/S0392-9590.18.03975-5
PMID: 29385792 [Indexed for MEDLINE]