Updated on 1 December 2014
Mr Sven Seyffert, senior business director, Aortic and Peripheral Vascular Business Unit, Medtronic, Asia Pacific
Singapore:Peripheral arterial disease (PAD) is caused by plaque that builds up in the arteries that carry blood to head, organs, and limbs and over time, plaque can harden and narrow the arteries, limiting the flow of oxygen-rich blood to different parts of the body. Worldwide, some two hundred million patients are estimated to suffer from the disease and although the incidence and prevalence of PAD are on the rise, the disease remains underdiagnosed and undertreated. The continued rise of PAD is attributed to increasing life spans and risk factors such as smoking, diabetes, obesity, high blood pressure, high cholesterol, and family history. PAD itself is a condition that causes reduced blood flow to one's extremities due to the buildup of plaque (fatty deposits), or atherosclerosis, along the walls of arteries. In extreme cases, this buildup can reach levels at which an impacted blood vessel is completely occluded causing the limb to be starved of blood, oxygen, and nutrients until its tissue dies and amputation is the option of last resort.
If diagnosed early, initial treatment will be conservative and non-invasive, consisting of medication to manage blood pressure, cholesterol, or diabetes. Exercise is also recommended. If the disease continues to progress and it becomes apparent that the atherosclerotic buildup must be addressed directly, a patient may undergo a number of different invasive and minimally invasive treatment options. The most invasive option is to bypass the affected segment of the artery through a synthetic graft or a vessel harvested from another part of the patient's body. While this treatment option tends to have good long-term outcomes if successful, it is also associated with long recovery times and considerable scaring.
Angioplasty approaches, a minimally invasive alternative, have become the most common way to address this plaque buildup directly. An angioplasty involves the insertion of catheters traveling along wires into the blood vessel until the atherosclerotic segment is reached. Once there, the treating physician has the option to inflate a small PTA (Percutaneous Transluminal Angioplasty) balloon to press the plague against the vessel wall or to take it one step further and implant a metal scaffolding, called a stent, that is designed to keep the plaque at bay for longer. Although these stents appear to be more efficacious with respect to maintaining vessel patency after 12 months (around 75-80 percent for stents versus in the 60s percent for balloons), stents are not only more expensive but they can be impractical depending on lesion length or location as vessels twist and bend during normal leg movements. This can result in stent kinking and fractures which, in turn, can injure the vessel wall and promote the growth of scar tissue which actually accelerates restenosis. While there are also stents that elute drugs designed to inhibit plaque regrowth (12-months patency rates can surpass eighty percent), their cost is even higher and the disadvantages of having a permanent metal scaffolding implanted remains.
Peripheral Drug Coated Balloons - A paradigm shift
It was clear that the technological leap required for a better solution would combine the improved efficacy of stents with the concept of leaving nothing behind to ensure better outcomes while keeping future treatment options open. The quest for such a solution gave rise to the concept of Drug Coated Balloons (DCBs) which are now ushering in a new era in the treatment of PAD. In April 2014, the results of a Medtronic randomized 331-patient, multi-center clinical trial spanning across 6 countries and 57 participating sites called the In.Pact SFA I and II were presented at the Charing Cross Symposium in London. This trial evaluated a Medtronic Drug Coated Balloon and found primary patency rates of 89.8 percent after 12 months! This result is unmatched by any randomized clinical trial across any treatment modality for PAD interventions and gives us great hope that many more patients can benefit from improved outcomes after PAD interventions. Higher patency rates lead to fewer re-interventions which, in turn, lowers the risk of infections and other complications as well as additional associated costs. From a health system perspective, fewer re-interventions also mean fewer hospital visits, lower cath lab utilization, and less physician time, decreasing the burden on health services utilization. Another big advantage of DCBs is that they can be seamlessly integrated into the clinical practice of any physician with the interventional skills needed to perform a conventional peripheral PTA balloon angioplasty.
In addition to certain differences in balloon technologies among companies, the improved efficacy of DCBs stems from the mechanism of action of the drug that coats the balloon and from the way that drug is delivered. The drug, called Paclitaxel, is transferred into the vessel wall upon balloon inflation. In the case of Medtronic's DCB, the Paclitaxel is delivered in the form of tiny crystals through a naturally occurring compound called Urea which acts as a hydrophilic excipient to facilitate vessel uptake. Over time, these crystals migrate deeper into the vessel wall and prevent restenosis-promoting cells from re-growing. While trace amounts of Paclitaxel can still be detected in the vessel wall for several months after balloon inflation, benefits remain even after it has been completely absorbed. Since the balloon acts as a highly targeted delivery platform, only tiny amounts of drug (about 3µg/mm2) are needed to achieve the desired effect. This means the drug does not need to be taken systemically and the toxicity profile is excellent.
I am particularly excited for patients in South East Asia to benefit from this new technology. We find that patients in this part of the world not only have significantly longer and more defused lesions, making stenting even less practical, they also tend to present at a younger age. This is presumably due to higher smoking rates, more uncontrolled diabetes, and more uncontrolled hypertension than we encounter in the Western world. As more physicians learn about and accept the tremendously promising DCB clinical data, I am confident that these devices will soon become the first line treatment option for PAD patients to ensure quality of life can be maintained and many limbs can be saved.