In November I attended the VEITHsymposium in New York. Almost 600 experts from around the world gave lectures on every aspect of vascular surgery. Given 5 minutes per talk, the presenters had to carefully select data they believed would bolster their viewpoint. So will someone please explain to me why some speakers still feel obliged to include target lesion revascularization (TLR) in their presentations? Furthermore, it’s not just in talks but also in peer-reviewed journals that we seem to be bombarded with this useless and often deceiving piece of information. I know that many feel the same way about TLR. However, for those not yet convinced, let me outline why I think TLR should rather stand for “The Least Relevant.”
The concept of TLR materialized during the early days of coronary balloon angioplasty and stenting. In the coronary arteries it is difficult to determine the restenosis rate of a treated lesion without repeating another coronary arteriogram. Accordingly, researchers resorted to TLR as an alternative method of evaluating whether a new treatment worked. However, in the peripheral circulation we have other methods of evaluating the lesion such as duplex scanning, CTA and MRA. This allows us minimally invasive and noninvasive means to evaluate the fate of the lesion itself. Thus, we are able to evaluate TLR as target lesion recurrence rather than target lesion revascularization.
Subsequently, companies and researchers have developed new devices such as balloons, stents, atherectomy devices, and drug-eluting variations that directly target peripheral vascular lesions. Despite the availability of noninvasive techniques to evaluate the target lesion itself, they use TLR data to convince physicians and purchasing entities to buy and use their device. The implication is that avoidance of another procedure to achieve the desired clinical endpoint proves that the new instrument works. However, as I have mentioned in previous editorials, semantics can have negative consequences. Here the problem arises when we attempt to define “works.” The inventor of a device that opens a narrowed or blocked artery wants to make sure that the device indeed does just that. In that case it would be appropriate to claim that it “works.”
If the lesion remains open and does not re-narrow we may conclude the device not only works but is also “effective.” The manufacturer and the FDA will want to make sure that it also does no harm and is “safe.” All are hopeful that it will improve the patient’s condition and have “clinical utility.” Certainly, success can be defined in many ways and clinical benefit must reign supreme. Accordingly, a device that is effective, safe and has clinical utility may be considered “successful” and, if cost effective, worth using. However, we are all aware that some procedures can improve a patient’s condition through a placebo effect. Therefore, it is incorrect for researchers to suggest that low TLR rates equate with clinical success. The most reliable judge of the efficacy of the procedure will be what happens to the targeted lesion and not what happens to the patient. It is more salient that we are assured that the device provides persistent improvement in luminal diameter at the site of the treated lesion.
It may help to further define the problem with TLR if we use a hypothetical example of a new medicated stent inserted to open a single SFA lesion responsible for toe gangrene. If that stent keeps the stenotic lesion widely patent, it should be considered effective even if the patient ultimately requires an above-knee amputation. On the other hand if the stent occludes in the recovery room, yet the toe subsequently heals without any further intervention, that stent did not work. In the latter scenario the patient will not have had a revascularization and so will not be included with the patients requiring TLR. Thus the stent would appear to have had more clinical utility or to have been more”successful” than it really was. Similarly, TLR will not be negatively impacted when, as in some circumstances of stent occlusion, a patient decides to live with discomfort rather than consent to another procedure. Furthermore, investigators of that stent may have a perverse incentive after occlusion to minimize TLR by not performing another procedure. On the other hand a bypass of an artery with an open and functional stent would negatively impact TLR statistics for that type of stent. This may occur if the stented lesion was not the only cause of distal ischemia.What concerns me most about TLR, even more than its limited relevance, is that this statistic is used to support data that otherwise would not stand up to scrutiny. It is often included in trials where numbers are small or where Industry bias is obvious. Accordingly, I am hopeful that researchers seriously consider describing TLR as target lesion recurrence rates omitting target lesion revascularization from their presentations and manuscripts. If they insist on using this irrelevant statistic then they should provide information as to why the revascularization was performed.
Was it for lesion recurrence or failure to improve the indicated condition? If the lesion recurred but TLR was not performed, was that because recovery had been achieved despite restenosis of the target lesion? Was it because the patient was not offered further treatment? Perhaps the patient succumbed before TLR could have been provided?
I may be accused of being overly cynical, but it may have been because the patient had decided that the better part of valor would be to run away and join a witness protection program rather than take part in that clinical trial.