Injectable Varithena Foam Therapy for Varicose Veins

An Interview With Marlin Schul, MD, MBA

Varithena (BTG) was approved by the US Food and Drug Administration (FDA) in 2013 to treat varicose veins caused by problems with the great saphenous vein (GSV) and other related veins in the GSV system of the legs. Varithena is a uniform, low-nitrogen, polidocanol microfoam dispensed from a proprietary canister device. The physician injects a small amount of Varithena into the malfunctioning vein through a small catheter or a needle. It displaces the blood from the vein to reach and treat the vein wall; the diseased vein collapses and blood flow is diverted to healthy veins nearby. Marlin Schul, MD, MBA, of the Lafayette Regional Vein & Laser Center in Indiana, conducted the first Varithena procedure in the United States in August 2014. Vascular Disease Management discussed the use of the foam with Dr. Schul.

Please describe the composition of the Varithena foam and its intended application.

Varithena is a form of polidocanol that is now commercially available. It became FDA approved in November and it’s an exciting addition to any serious vein practice. When you look at its applications it’s very simple. Great saphenous incompetence affects a large number of people in this country and this is meant to treat saphenous incompetence from the saphenofemoral junction, including the GSV, anterior accessory, posterior accessory, as well as varicose veins along those saphenous tributaries. When it comes to the mechanism of action it does a wonderful job of creating a spasm of the vessel as well as maintaining a column of concentrated foam that will destroy the lining of the vein wall within seconds and cause an inflammatory response that allows that vessel to close. Generally speaking when you compare this to other types of sclerosis, it’s a far more safe and efficacious tool to use at this time.

Are data available on safety and efficacy?

Among the trials done, the VANISH-1 and VANISH-2 are among the more recent. The safety is one of the things that I think is most important because there were no major complications. There was no clinically important neurologic or visual adverse event suggestive of cerebral gas embolism seen in any of the patients treated with Varithena.

It’s important to understand the safety of any sclerosant because many providers with a pure surgical background may fear the use of foam. Image guidance is imperative to allow adequate visualization to track where everything communicates and not only assure that the target vein has been exposed, but that normal veins have been protected. With proper care, it’s an incredibly safe tool to employ, though it does have a learning curve. 

When it comes to efficacy, I’ve been treating veins for over 12 years and I started by using sclerosants to treat veins. Although you can treat incompetent saphenous veins and close them with a number of different sclerosants, it requires far more treatment sessions with far greater side effect profiles than what Varithena presents. So if you were to look at the efficacy results in recent trials, 80% of people had complete closure of the target vessels with one treatment and that’s pretty striking for a sclerotherapy agent. All of the patients that I treated as part of a phase-3 FDA trial using Varithena said they would do it again. When it came to what I was able to see on those patients with regards to their symptom control and what we saw on Duplex not every patient had the same response, of course, because we were using a variety of different concentrations; it was a randomized and blinded trial. At the same time, when we discovered what we initially gave these patients I was quite impressed as far as the response we saw even to some of the lesser concentrated chemicals. 

When you look at efficacy you have to look at a couple of different things. Are you talking about closure of the vein or are you talking quality-of-life improvement? The surrogate outcome of vein closure with one treatment at 80% is pretty strong, but when you look at quality-of-life benefits that these patients reported, I think that’s even more striking. It seems as though much of the research available compares device A to device B in terms of results on ultrasound, not necessarily in terms of benefit to the patient when it’s done. And that’s the one thing that the research behind Varithena has brought forth clear as can be: the patients treated with Varithena can have a very significant change in their quality of life for the positive. 

What challenges facing physicians treating varicose veins can Varithena help overcome?

There are challenges that come to mind depending upon your interpretation of the law. If we are supposed to use an FDA-approved chemical, if available, then the only FDA-approved foam is Varithena. For specialists who have been using liquid sclerotherapy and finding limitations to liquid sclerotherapy because of fear of using self-compounded foam for variety of reasons, some of which are medicolegal, this is an ideal transition because providers may actually enhance their efficacy using chemical ablation but with a tool that’s safer and more efficacious. 

Other challenges that vein specialists face are that some use only a few tools — let’s say those tools are a scalpel and a radiofrequency catheter. Those who are limiting their treatment options to just the catheter and a small incision are not necessarily meeting all of their patients’ needs. This may lead to recurrent disease because residual disease will be left behind, ultimately not allowing for comprehensive treatment.

I use endovenous laser, radiofrequency, ambulatory phlebectomy, as well as a variety of sclerosants. I think my utilization of a number of these will change with the availability of Varithena. This particular agent will have a far greater reach than the other tools will have because it has more indications. You can only do phlebectomy on veins that you see close to the surface. You can only treat with thermal ablation those vessels that are long and straight. Varithena gives you options that will likely be requested by patients as time goes on, but it also offers a new tool to providers when they can’t justify phlebectomy or when a patient isn’t suited to thermal ablation due to comorbidities or other factors.  

What benefit to patients is offered with the availability of Varithena? 

For the population of patients seeking cosmetic therapy, they generally want things done in a timely way. In other words, traditional surgical stripping is not what they’re after. They want procedures that offer less down time, that are less invasive, and that are patient friendly. Varithena offers that option to those patients. You also have the medically needy patients who may not, due to comorbidities, be able to be on an operating table for the same duration of time to, for instance, treat an anterior accessory and GSV and tributaries. If you can treat them and achieve similar results using Varithena, then you provided a safer treatment to those patients. Many patients do find relief with other treatments, but I think that Varithena is certain to provide relief of symptoms.

Are there still challenges to using foam therapies for varicose veins?

Insurers often fail to understand the benefits of chemical ablation. Chemical ablation, which includes Varithena, is sometimes considered cosmetic, and that’s just not the case. We need a wealth of data to showing continual quality-of-life benefit so that insurers can see the effectiveness beyond vein closure, whether it’s Varithena or other treatments. Evidence of benefit is something that’s lacking right now and it certainly represents a challenge for almost any vein treatment moving forward.

Is there any result of Varithena that was particularly impressive to you?

We saw patients with a variety of different concerns. This is different than anything I’ve used before. It creates a tremendous spasm, and between ultrasound findings and patient reporting as we marched through that trial I was impressed, and I had no preconceived expectations.

And are there any questions that still need to be answered that might be answered with future research?

I think it goes back to the challenges. I think the future of vein treatment involves more data on the benefits of the work that we do and right now that’s lacking in a large way -- not just among vein treatment specialists but nearly any specialist. Registries offer the most effective way to discover gains that patients perceive. There has certainly been pressure from the Society of Vascular Surgery, the American Venous Forum, and the American College of Phlebology to encourage registry participation. I believe that if we couple outcomes of what we see as clinicians with what the patient reports that those questions will help identify patients who stand to benefit more, for instance, than others and which treatments might be more effective in achieving that outcome. That’s not going to be answered tomorrow, but I certainly think that Varithena has shown tangible benefits as reported by those treated.

Is there anything else that you wanted to add?

I would like to finish by sharing that venous reflux disease is more than a cosmetic concern. Not all legs are the same, and if you’re going to treat veins on a regular basis, you need to have more than one tool in the toolbox to do the job. That leads to where Varithena plays a role. If a provider is going to be using a foam, and they’re obligated to use an FDA-approved product, I think they’re going to be happy with this choice.

Marlin W. Schul, MD, MBA, is the director of the Lafayette Regional Vein & Laser Center in Lafayette, Indiana. He is board certified by the American Board of Phlebology and the American Board of Emergency Medicine. He is a Fellow of the American College of Phlebology. Dr. Schul reports consultancy to, involvement in the VANISH-2 trial for, and reimbursements related to educational presentations from Varithena.