Paclitaxel Focus of Device Controversy

The technology behind percutaneous treatment for the coronary arteries has advanced much more rapidly than for the peripheral vasculature, but the use of paclitaxel, a chemotherapeutic agent, as a go-to antiproliferative for any part of the anatomy could be near an end. The FDA published a letter to physicians in January stating that a medical journal article suggested that paclitaxel-bearing drug-eluting stents (DESs) and drug-coated balloons (DCBs) for the peripheral arteries had demonstrated an unexpectedly high long-term mortality rate compared to bare-metal stents and non-coated balloons. However, the conclusions drawn in that medical journal are the subject of a dispute that may determine whether paclitaxel has any future at all in the circulatory system.

The article in the Journal of the American Heart Association describes a meta-analysis covering more than two dozen randomized, controlled trials for both DES and DCB devices, all coated with paclitaxel. The authors stated that all-cause death at both two and five years for paclitaxel devices was significantly higher than for their non-eluting counterparts when used in the arteries of the lower extremities, but that more study is warranted, in part because only two of those studies ran for a full five years. The authors hypothesize that the crystalline form of paclitaxel, which has a longer half-life than other formulations, may be the culprit.

Medtronic, the Dublin-based manufacturer of the In.Pact Admiral DCB, took issue with the JAHA authors in an article in the Journal of the American College of Cardiology, stating that there is no statistically significant difference in mortality between DCBs and plain angioplasty balloons at five years. As is the case with the JAHA analysis, there are a number of moving parts in the Medtronic summary, including that the data are drawn from patients in a variety of nations that exhibit different patterns of post-procedural care, not to mention differences in the use of dual anti-platelet therapy (DAPT). The company argued that much of the difference in mortality outcomes could hinge on the more aggressive use of DAPT in patients treated with bare-metal stents and plain angioplasty balloons.

Whether any of this clinical data will translate into regulatory action is impossible to forecast, but the FDA advised that it still sees the benefit of these devices as outweighing the risks. If Medtronic’s view – that the mortality rates at five years out, at least in statistical terms – wins the day, device makers might be on the hook for nothing more than a somewhat greater post-market surveillance liability. Makers of DCBs might already be on that track, as the Centers for Medicare & Medicaid Services (CMS) declared it will pay what clinicians and device makers see as a sub-optimal rate for these devices, unless and until CMS sees some compelling data that the difference in cost between DCBs and plain balloons is justified by outcomes.