Despite the widespread acceptance of percutaneous methods for treating lower extremity peripheral arterial disease, there exist few studies that objectively assess the benefits of such intervention in comparison to standard therapy. In this regard, the Foxhollow company should be congratulated for its boldness in planning a randomized comparison of Silverhawk plaque excision versus surgical bypass in patients with limb-threatening ischemia. The PROOF study will be designed with amputation-free survival as the primary endpoint; again, an excellent choice on the part of the company.
Foxhollow’s decision to perform a second study, the SWIFT non-randomized registry of patients undergoing atherectomy seems unwise. In this study; the planned endpoints of patency and restenosis are of little value without a concurrent control arm. Comparison to historical controls is difficult – especially given differences in baseline patient characteristics such as lesion length, degree of stenosis, and concomitant antiplatelet or statin therapy. In fact, the SWIFT study appears remarkably similar to the company’s prior TALON trial; with the few exceptions of core laboratory analysis and objective imaging for patency determinations.
Of course, the true competitors of atherectomy are balloon angioplasty and stenting. And, these three modalities (Silverhawk, POBA, and stenting) are most often used in patients with significant limiting claudication. Thus, the most valuable trial would be a randomized comparison of Silverhawk atherectomy with balloon or stent, using an objective and (most importantly) meaningful endpoint such as walking distance at one year. Patency and ankle brachial index would be important secondary endpoints, but should not be primary.
But, back to the PROOF trial, this randomized comparison of Silverhawk versus surgical bypass is reasonable, and no endpoint could be more objective than amputation-free survival. However, the use of this endpoint mandates an appropriately long duration of follow-up. The reason for this becomes evident when one realizes that the risk of amputation with observation alone is not high – at least early on. And, few would argue that a percutaneous therapy is associated with lower mortality than surgical bypass. So, the price of a greater periprocedural mortality rate with bypass must be repaid over time with improved limb salvage. Choosing to assess amputation-free survival early on, for example at one-year, would tend to artificially favor atherectomy on the basis of a lower periprocedural mortality rate. Not waiting long enough for atherectomy failures to result in limb loss will bias the results in favor of Silverhawk, just as even observation alone would ‘beat’ surgery with respect to amputation-free survival early on.
In summary, among the two studies on the docket for Foxhollow, the SWIFT registry seems redundant, with little potential to provide new information. By contrast, the PROOF trial appears quite useful provided patients with true limb threatening ischemia are enrolled and provided that the planned six month and one year interim analyses are abandoned in favor of longer, more meaningful assessments.