Unlike alarming evidence suggesting an increased risk of death with the use of paclitaxel-coated balloons and stents in the peripheral, a meta-analysis of 26 randomized controlled trials and 4,590 patients finds no increased risk of mortality when drug-coated balloons (DCBs) were used in coronary arteries.
DCBs are a guideline-recommended treatment strategy for in-stent restenosis (ISR) and are under clinical investigation for lesions without prior stent implantation.
This is good news given that the peripheral field was recently shaken by data from a large meta-analysis suggesting that the use of paclitaxel-coated devices to treat peripheral artery disease (PAD) was associated with a higher risk of all-cause late mortality – at both 2 years and up to 5 years – compared with alternative therapeutic modalities. (The mortality signal was confirmed by independent analyses of the U.S. Food and Drug Administration.)
Just a little over 1 year after publication of the PAD data, Bruno Scheller, MD, University of Saarland, Homburg, Germany, and colleagues now report their coronary results in the Journal of the American College of Cardiology. In contrast to the PAD experience with paclitaxel-coated devices for superficial femoral artery interventions, paclitaxel-coated coronary balloons were associated with trends toward lower mortality at 6 to 12 months and 2 years compared with control treatments. This difference favoring DCB use reached significance at 3 years (relative risk [RR]: 0.73; p = 0.047) with a similar reduction seen in cardiac mortality (RR: 0.53; p = 0.009).
For total mortality, the number needed to treat was 36 to prevent 1 death. By contrast, the all-cause mortality data from the peripheral meta-analysis showed a number‐needed‐to‐harm of 29 patients at 2 years and 14 patients at up to 5 years.
Given the large number of patients analyzed, the authors were able to perform a comprehensive set of subanalyses to further confirm the robust safety data in the coronaries.
Difficult to Explain
The authors of the original PAD paper and now the coronary meta-analysis authors all find it difficult to explain the PAD results. Paclitaxel concentrations in the vessel wall immediately after DCB inflation are high and serve as a reservoir. But the dose administered by a coronary DCB is approximately 750 times lower than that of systemic cancer therapy with paclitaxel, challenging the plausibility of a drug effect when local therapies do not have systemic effects.
In an accompanying commentary to the JACC paper, Fernando Alfonso, MD, PhD (Hospital Universitario de La Princesa, Madrid, Spain), and colleagues noted that as paclitaxel-coated balloons were becoming the standard of care for interventions in the femoral region, the
unexpected results of the first meta-analysis fueled a heated controversy. Fierce critics highlighted major methodological shortcomings of the study plus the lack of any plausible pathophysiological explanation.
Alfonso and his coauthors noted that the mortality benefit of paclitaxel-coated balloons was mainly driven by de novo lesion data, an indication less well-established than ISR. Consequently, they wrote, the mortality benefit should only be considered hypothesis-generating, yet it reinforces the safety of these balloons for selected patients with lesions in native coronary vessels.
They added that the long-term safety data from the coronary study is important given that most previous randomized controlled trials were not adequately powered to be completely reassuring regarding safety. The results also complement the available clinical evidence of these balloons curbing restenosis in patients with coronary ISR and de novo lesions.
Overall, they noted that the data reassure the safety of coronary revascularization with paclitaxel-coated balloons.
Scheller B, Vukadinovic D, Jeger R, et al. Survival After Coronary Revascularization With Paclitaxel-Coated Balloons. J Am Coll Cardiol 2020;75:1017-1025. http://www.onlinejacc.org/content/75/9/1017
Alfonso F, Rivero F, Granada JF, et al. Safety of Paclitaxel-Coated Balloons in the Coronary Arteries. J Am Coll Cardiol 2020;75:1029-1032. http://www.onlinejacc.org/content/75/9/1029
Katsanos K, Spiliopoulos S, Kitrou P, Krokidis M, Karnabatidis D. Risk of death following application of paclitaxel-coated balloons and stents in the femoropopliteal artery of the leg: a systematic review and meta-analysis of randomized controlled trials. J Am Heart Assoc 2018;7:e011245. https://www.ahajournals.org/doi/full/10.1161/JAHA.118.011245