Vessel Occlusion: There’s no room for complacency

There is nothing new about cardiovascular disease leading to occluded blood vessels. The consequences are well understood. Today, patients should expect quick and accurate diagnosis and treatment. But all is not well and it is our responsibility to always strive to avoid complacency.

The cardiovascular disease problem leading to vessel occlusion (blockages) is not fully solved. Many patients enjoy the benefit of less invasive drug-eluting stents to resolve their disease-induced blocked arteries, we are remiss if we simply say that what we have today is good enough, problem solved.

With many years of experience in vascular devices, I have followed this topic with great interest. Should we as manufacturers, surgeons and medical device companies accept the status quo?

How the risks grew and unfolded

Surgical bypass was, and still is, a solution. Surgical bypass, be that for coronary or peripheral disease, was partly replaced by less invasive interventional techniques, from balloon angioplasty, to bare metal stents and then onto the drug eluting stents that were actually developed to address the complications associated with bare metal stent.  Bioresorbable stents was a diversification, has promised much, but as yet has not delivered.

But what is the mechanism causing these problems? Any foreign body can and will initiate our defence and protective reactions, our immune system. A stent is no different. It may be a therapeutic device, aiming to overcome the consequences of a blocked blood vessel, but our body’s alarm system goes off in an attempt to ward off this invader.

Platelets are activated, thrombus results, smooth muscle cells proliferate in an attempt to encapsulate the invader, and the result is vessel re-occlusion through thrombus formation and re-stenosis inside the stent. The patient is back to square one.

Enter stage left the drug-eluting stent. As we slipped into the 21st century, the solution to re-occlusion of bare metal stents was the drug eluting stent, where the stent is coated with a slow-release medication to help stop blood clots and smooth muscle ingress inside the stent.

Voila! Local delivery of drug eluting agents, and particularly Paclitaxel, for coronary & peripheral stents, has been shown to reduce restenosis rates and percent diameter stenosis compared to bare metal stents.

Problem solved!

Until, that is, enter stage right, Konstantinos Katsanas and colleagues, toward the end of 2018:

“There is increased risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the lower limbs.”

As a vascular surgeon friend of mine commented, the Katsanos paper on paclitaxel has prompted much angst among medical device companies, surgeons and regulatory bodies over the last couple of years.

If peripheral stent manufacturers were getting comfortable about the issue of increased mortality as time progressed, Katsanos et al came screaming back in mid-2021:

“There appears to be heightened risk of major amputation after use of paclitaxel coated balloons in the peripheral arteries.”

The evidence is compelling. When comparing paclitaxel-coated devices with controls, the all-cause death rate approached double that of the control for paclitaxel-coated devices. As time goes on, the difference widens.

And for the statisticians, Katsanos etal concluded “meta-regression showed a significant relationship between exposure to paclitaxel and absolute risk of death”.

Let’s remember here, Katsanos etal research and evidence comes from re-evaluating clinical trial data, with carefully selected inclusion criteria, and not performance in general – unreported – clinical use.

Maybe the evidence is not totally clear, and many have argued against the findings, and as my friend also commented, there are many competing sets of data with conflicting conclusions.

In amongst all of this reporting, debate and manufacturer justification, moving centre stage, the FDA. Into this script comes an FDA warning letter in January 2019 and a list of approved paclitaxel coated balloons and eluted stents to treat arteries of the legs in December 2021.

The FDA letter provided a warning to health care providers about the late mortality signals in patients treated for peripheral arterial disease with paclitaxel coated balloons and drug eluting stents. The warning did recognise that many patients have benefitted from these devices but the FDA requires careful case selection with mandatory long-term monitoring and follow up.

One result has been that patients must be informed of the benefits and risks associated with paclitaxel before any surgery. A friend of mine operating in a very prestigious hospital has to complete a separate patient consent to use a paclitaxel coated device.

Do paclitaxel-coated peripheral stents have a future?

At the coal face, the use of paclitaxel-coated peripheral stents has plummeted and has not shown a recovery back to previous levels. For patients with peripheral arterial disease, globally, that is an astonishingly large and growing number of people left with an arguably preferred treatment option that solves their initial problem – disease induced arterial occlusion – but may create a secondary, catastrophic, complication – therapy induced arterial occlusion, an increased risk of dying and a heightened risk of amputation.

As I say, no place for complacency!

Maybe manufacturers have re-evaluated their paclitaxel product performance to say that all is OK. Perhaps because of the cost of finding the next generation solution or because of the apparent absence of a suitable next generation way forward.

Well seek a solution we must, that’s our responsibility and our legacy.

Risk and return are linked but complacency is not a risk position that will build return. It simply supports a status quo.

Time to move on industry!