Varithena® is a recently approved commercially available drug/delivery unit that produces foam using 1% polidocanol for the management of varicose veins. The purpose of this review is to examine the benefits of foam sclerotherapy, features of the ideal foam sclerosant and the strengths and limitations of Varithena® in the context of current foam sclerotherapy practices.
Method
Electronic databases including PubMed, Medline (Ovid) SP as well as trial registries and product information sheets were searched using the keywords, ‘Varithena’, ‘Varisolve’, ‘polidocanol endovenous microfoam’, ‘polidocanol’ and/or ‘foam sclerotherapy/sclerosant’. Articles published prior to 20 September 2016 were identified.
Results
Foam sclerosants have effectively replaced liquid agents due to their physiochemical properties resulting in better clinical outcomes. Medical practitioners commonly prepare sclerosant foam at the bedside by agitating liquid sclerosant with a gas such as room air, using techniques as described by Tessari or the double syringe method. Such physician-compounded foams are highly operator dependent producing inconsistent foams of different gas/liquid compositions, bubble size, foam behaviour and varied safety profiles. Varithena® overcomes the variability and inconsistencies of physician-compounded foam. However, Varithena® has limited applications due to its fixed sclerosant type and concentration, cost and lack of worldwide availability. Clinical trials of Varithena® have demonstrated efficacy and safety outcomes equivalent or better than physician-compounded foam but only in comparison to placebo alone.
Conclusion
Varithena® is a promising step towards the creation of an ideal sclerosant foam. Further assessment in independent randomised controlled clinical trials is required to establish the advantages of Varithena® over and above the current best practice physician-compounded foam.
National Institute for Health and Care Excellence (2013) CG168 Varicose veins in the legs: the diagnosis and management of varicose veins. Manchester: NICE, www.nice.org.uk/CG168 (accessed October 2015).
DuffyDM. Sclerosants: a comparative review. Dermatol Surg2010; 36: 1010–1025.
4.
WongKChenTConnorDEet al.Basic physiochemical and rheological properties of detergent sclerosants. Phlebology2015; 30: 339–349.
5.
ConnorDECooley-AndradeOGohWXet al.Detergent sclerosants are deactivated and consumed by circulating blood cells. Eur J Vasc Endovasc Surg2015; 49: 426–431.
6.
ParsiKExnerTConnorDEet al.The lytic effects of detergent sclerosants on erythrocytes, platelets, endothelial cells and microparticles are attenuated by albumin and other plasma components in vitro. Eur J Vasc Endovasc Surg2008; 36: 216–223.
7.
WatkinsMR. Deactivation of sodium tetradecyl sulfate injection by blood proteins. Eur J Vasc Endovasc Surg2011; 41: 521–525.
8.
Cooley-AndradeOConnorDMaDet al.Morphological changes in vascular and circulating blood cells following exposure to detergent sclerosants. Phlebology2016; 31: 177–191.
9.
ParsiKExnerTLowJet al.In vitro effects of detergent sclerosants on antithrombotic mechanisms. Eur J Vasc Endovasc Surg2009; 38: 220–228.
10.
ParsiKExnerTConnorDEet al.In vitro effects of detergent sclerosants on coagulation, platelets and microparticles. Eur J Vasc Endovasc Surg2007; 34: 731–740.
11.
ParsiKExnerTLowJet al.In vitro effects of detergent sclerosants on clot formation and fibrinolysis. Eur J Vasc Endovasc Surg2011; 41: 267–277.
12.
ParsiKConnorDEPilotelleAet al.Low concentration detergent sclerosants induce platelet activation but inhibit aggregation due to suppression of GPIIb/IIIa activation in vitro. Thromb Res2012; 130: 472–478.
13.
ConnorDEJosephJEExnerTet al.Infusion of foam sclerosants results in a distance-dependent procoagulant activity, haemoconcentration and elevation of D-dimer levels. Phlebology2014; 29: 677–687.
14.
WollmannJC. The history of sclerosing foams. Dermatol Surg2004; 30: 694–703.
15.
OrbachEJ. Sclerotherapy of varicose veins: utilization of an intravenous air block. Am J Surg1944; 66: 362–366.
16.
TessariL. Nouvelle technique d'obtention de la scléro-mousse. Phlébologie2005; 53: 129.
17.
TessariLCavezziAFrulliniA. Preliminary experience with a new sclerosing foam in the treatment of varicose veins. Dermatol Surg2001; 27: 58–60.
18.
ValenzuelaGCWongKConnorDEet al.Foam sclerosants are more stable at lower temperatures. Eur J Vasc Endovasc Surg2013; 46: 593–599.
19.
CameronEChenTConnorDEet al.Sclerosant foam structure and stability is strongly influenced by liquid air fraction. Eur J Vasc Endovasc Surg2013; 46: 488–494.
20.
ShiraziARGoldmanM. The Use of a 5-μm filter hub increases foam stability when using the double-syringe technique. Dermatol Surg2008; 34: 91–92.
21.
CavezziATessariL. Foam sclerotherapy techniques: different gases and methods of preparation, catheter versus direct injection. Phlebology2009; 24: 247–251.
22.
ParsiK. Paradoxical embolism, stroke and sclerotherapy. Phlebology2012; 27: 147–167.
23.
MaRWPilotelleAParaskevasPet al.Three cases of stroke following peripheral venous interventions. Phlebology2011; 26: 280–284.
24.
GilletGL. Neurological complications of foam sclerotherapy: fears and reality. Phlebology2011; 26: 277–279.
25.
TessariLCavezziATessariMet al.Timing and modality of the sclerosing agents binding to the human proteins: laboratory analysis and clinical evidences. Veins Lymphatics2014; 3: 3275.
26.
FrulliniABarsottiMCSantoniTet al.Significant endothelin release in patients treated with foam sclerotherapy. Dermatol Surg2012; 38: 741–747.
27.
HesseGBreuFXKuschmannAet al.Sclerotherapy using air- or CO2-O2 foam: post-approval study. Phlebologie2012; 41: 77–88.
28.
BeckittTElstoneAAshleyS. Air versus physiological gas for ultrasound guided foam sclerotherapy treatment of varicose veins. Eur J Vasc Endovasc Surg2011; 42: 115–119.
29.
MorrisonNNeuhardtDLRogersCRet al.Incidence of side effects using carbon dioxide-oxygen foam for chemical ablation of superficial veins of the lower extremity. Eur J Vasc Endovasc Surg2010; 40: 407–413.
30.
MorrisonNNeuhardtDLRogersCRet al.Comparisons of side effects using air and carbon dioxide foam for endovenous chemical ablation. J Vasc Surg2008; 47: 830–836.
31.
RabeEBreuFXCavezziAet al.European guidelines for sclerotherapy in chronic venous disorders. Phlebology2014; 29: 338–354.
BreuFXGuggenbichlerS. European consensus meeting on foam sclerotherapy, April, 4–6, 2003, Tegernsee, Germany. Dermatol Surg2004; 30: 709–717.
34.
NastasaVSamarasKAmpatzidisCet al.Properties of polidocanol foam in view of its use in sclerotherapy. Int J Pharm2015; 478: 588–596.
35.
BhowmickAHarperDWrightDet al.Polidocanol microfoam sclerotherapy for long saphenous varicose veins. Venous Forum Phlebol2001; 16: 41–50.
36.
WrightDGobinJPBradburyAWet al.Varisolve(R) polidocanol microfoam compared with surgery or sclerotherapy in the management of varicose veins in the presence of trunk vein incompetence: European randomized controlled trial. Phlebology2006; 21: 180–190.
37.
WrightDDIMcCollumCNTristramSet al.A single-centre pilot study of polidocanol endovenous microfoam treatment to evaluate the presence and durability of gas emboli using echocardiography. Phlebology2009; 24: 85–95.
38.
ReganJDGibsonKDRushJEet al.Clinical significance of cerebrovascular gas emboli during polidocanol endovenous ultra-low nitrogen microfoam ablation and correlation with magnetic resonance imaging in patients with right-to-left shunt. J Vasc Surg2011; 53: 131–137.
39.
PatyJTurner-BowkerDMElashCAet al.The VVSymQ(R) instrument: use of a new patient-reported outcome measure for assessment of varicose vein symptoms. Phlebology2016; 31: 481–488.
40.
Vasquez M, Gasparis AP and Varithena® 017 Investigator Group. A multicenter, randomized, placebo-controlled trial of endovenous thermal ablation with or without polidocanol endovenous microfoam treatment in patients with great saphenous vein incompetence and visible varicosities. Phlebology. Epub ahead of print 7 March 2016. DOI: 0268355516637300.
41.
KingJTO'ByrneMVasquezMet al.Treatment of truncal incompetence and varicose veins with a single administration of a new polidocanol endovenous microfoam preparation improves symptoms and appearance. Eur J Vasc Endovasc Surg2015; 50: 784–793.
42.
ToddKLIIIWrightDI. The VANISH-2 study: a randomized, blinded, multicenter study to evaluate the efficacy and safety of polidocanol endovenous microfoam 0.5% and 1.0% compared with placebo for the treatment of saphenofemoral junction incompetence. Phlebology2014; 29: 608–618.
Gibson K, Kabnick L and Varithena® 013 Investigator Group. A multicenter, randomized, placebo-controlled study to evaluate the efficacy and safety of Varithena® (polidocanol endovenous microfoam 1%) for symptomatic, visible varicose veins with saphenofemoral junction incompetence. Phlebology. Epub ahead of print 24 March 2016. DOI: 0268355516635386.
46.
CarugoDAnkrettDNZhaoXet al.Benefits of polidocanol endovenous microfoam (Varithena®) compared with physician-compounded foams. Phlebology2016; 31: 283–295.
47.
CarugoDAnkrettDO'ByrneVet al.The role of clinically-relevant parameters on the cohesiveness of sclerosing foams in a biomimetic vein model. J Mater Sci Mater Med2015; 26: 258.
48.
CarugoDAnkrettDNO'ByrneVet al.A novel biomimetic analysis system for quantitative characterisation of sclerosing foams used for the treatment of varicose veins. J Mater Sci Mater Med2013; 24: 1417–1423.
49.
CarugoDAnkrettDNZhaoXet al.Benefits of polidocanol endovenous microfoam (Varithena®) compared with physician-compounded foams. Phlebology2016; 31(Suppl.): 1–11.
Veteran Affairs Pharmacy Benefits Management Services (PBM), Medical advisory panel (MAP), and VISN pharmacist executive. Polidocanol (Asclera® and Varithena®) National Drug Monograph, May 2014, www.Pbm.va.gov (accessed August 2016).
53.
WrightDDPatyJTurner-BowkerDMet al.Psychometric evaluation of a new patient-reported outcome (PRO) Symptom diary for varicose veins: VVSymQ(®) Instrument. Patient2016; 9: 335–348.
54.
ToddKLIIIWrightDIGibsonKet al.Durability of treatment effect with polidocanol endovenous microfoam on varicose vein symptoms and appearance (VANISH-2). J Vasc Surg Venous Lymphat Disord2015; 3: 258–264.
55.
CavezziAParsiK. Complications of foam sclerotherapy. Phlebology2012; 27: 46–51.
56.
KulkarniSRMessengerDESlimFJet al.The incidence and characterization of deep vein thrombosis following ultrasound-guided foam sclerotherapy in 1000 legs with superficial venous reflux. J Vasc Surg Venous Lymphat Disord2013; 1: 231–238.
57.
KaneKFisherTBennettMet al.The incidence and outcome of endothermal heat-induced thrombosis after endovenous laser ablation. Ann Vasc Surg2014; 28: 1744–1750.
58.
KulkarniSRMessengerDESlimFJet al.The incidence and characterization of deep vein thrombosis following ultrasound-guided foam sclerotherapy in 1000 legs with superficial venous reflux. J Vasc Surg Venous Lymphat Disord2013; 1: 231–238.
59.
Harlander-LockeMJimenezJCLawrencePFet al.Management of endovenous heat-induced thrombus using a classification system and treatment algorithm following segmental thermal ablation of the small saphenous vein. J Vasc Surg2013; 58: 427–431.
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
