We Need to Compare Devices for Lower-Limb Revascularization

August 30, 2016

Lawrence A. Garcia, MD
From St. Elizabeth’s Medical Center, Brighton, Massachusetts.

Peripheral vascular disease is an ever-growing epidemic in the United States and throughout the world.1,2 Previous methods of therapy using medicine and exercise to the point of risk, critical limb ischemia, or rest symptoms and then performing an open surgical revascularization have been replaced with a revascularize-first approach. Principally, revascularization has been an endovascular-first approach that has become the standard of care, supplanting surgical revascularization as the default first-line therapy. 

Fortunately, there has been a large increase in the scientific data to support many, if not all, of the devices approved by the US Food and Drug Administration (FDA) and currently in use for lower-extremity revascularization in both the above- and below-knee territories.3-10 Unfortunately, there remains no good data set to compare one device to another, because most devices and their data, either the pivotal trial or subsequent registries, are driven only for approval, rarely compare to another revascularization strategy, and never compare to another device. Because of this conundrum there remains no “gold standard” for any one therapy or target of therapy. This glaring failure of the scientific community leads to the inability to choose one device over another for a particular lesion subset and, more importantly, an inability to discuss clearly with our patients which choice is “best” to treat their current obstructive disease. 

In trying to identify the best choice for a given situation, challenges arise involving trial endpoints. We have, unfortunately, accepted trial outcomes with use of nonbinary results. In the past, the goal of any revascularization was primary patency. However, the outcomes in lower-limb endovascular therapies have been held to a standard from surgical literature for primary patency that was more assisted primary patency rates. This has shoehorned endovascular outcomes into a combination of target lesion revascularization and primary patency with the use of Kaplan-Meier estimates of patency. 

The usefulness of this patency measurement is degraded further by its use in trial outcome reporting. For example, most trials use a 12-month endpoint for their 1-year patency. One would expect this to mean that the cohort of patients in any trial would be assessed at 12 months, and the number reported would be the outcome for the cohort at 12 months. However, in practice, the 12-month endpoint is a firm endpoint of those that have been assessed, likely through ultrasound outcomes, and those subjects not yet assessed are presumed patent at that time point. This is true of all current trial designs and outcomes, and it is one of the biggest failures in our reporting of data. If one reviews the final assessments at the 14-month endpoint (the point where all subjects have been assessed), the outcomes of every trial are drastically different than what was reported initially (as in the Zilver PTX, IN.PACT, and SUPERB trials). In some cases, the 12-month “reported” outcome is more than 10% different from the 14-month outcome (for example, IN.PACT). In other words, in some cases, the subjects who were evaluated as patent within the first window may present later in the reporting phase of the 14-month window, thereby decreasing the overall patency. Or, as in a recently reported study, because of a subject drop-out after the 9-month patency report, the patency actually went up at the 12-month endpoint.11 

If we as scientists can take these issues into consideration and understand there are always discrepancies across all trials regarding subjects enrolled and outcomes reported, we may begin to understand the limitations of the structure of outcome reporting. In this way we may glean the most important point from any trial: its true outcomes. With that understanding, if we review major trials with the 14-month endpoint as the final 1-year outcome, every major trial to date in the SFA has had a “primary patency” between 73% and 79%.7-9 It is remarkable that despite the heterogeneity of the subjects as to race, risk factors, and so on, all primary patency rates fall in the same range. A recent review in Circulation12,13 presented a debate format arguing for one device over another and discussed the related issues. These data are the best we have in the infrainguinal segment, and all trials/registries described have moved the scientific data set forward and should be commended for doing so. However, no one device has been studied using direct comparator designs against any other device except for simple angioplasty.3-6

The water becomes even muddier when the additional “registries” are then reviewed beyond the pivotal trial.14-16 To some extent, all major trials have randomized controlled trial (RCT) subjects that generally represent the outcomes in the strictest sense, or the “best” subjects that can be treated with a particular device. However, in some cases, registries have a full 10% increase in primary patency compared to the RCT,16 and in one case there was no difference in the primary patency from the RCT for lesion lengths over 3 times the length of those tested in the RCT.15 These successes fail to mention the critical finding in the registry of an ever increasing use of stenting in their outcome primary patency. This raises a question: is this a device registry, or a stent registry, or both? 

What may be clear to some remains unclear to many. The unfortunate reality for lower-extremity revascularization is that the scientific pursuit of what is “best” remains mired in a data set that currently cannot identify a victor. The “winners” are identified anecdotally, and not in direct comparator trials. This may change with the IMPERIAL trial sponsored by Boston Scientific, which is now half enrolled and will compare the Eluvia drug-eluting stent (Boston Scientific) to the Zilver PTX drug-eluting stent (Cook Medical). We look forward to this trial because it sets the stage for other devices to fully compare themselves to the other devices currently on the market. These trials work toward the same goal of all interventionalists: patient satisfaction, safety, and durability in endovascular revascularization.  

Editor's note: Dr. Garcia reports research for Abbott, Medtronic, noncompensated advising for Boston Scientific, equity in Arsenal, Primacea, Tissue Gen, CV Ingenuity, Spirox, Scion CV, Syntervention, and Essential Medical, and owndership of Innovation Vascular Partners Consulting. He reports having served as the national or global principal investigator for two studies described herein, including SUPERB and DEFINITIVE LE.

Original article source: Garcia LG. We need to compare devices for lower-limb revascularization. Vasc Dis Manag. 2016;13(9):E217-E219.


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