Drug-coated balloons (DCBs) have come to market as a promising tool to improve patency after endovascular revascularization for femoropopliteal arterial lesions. One major advantage of DCB angioplasty over stent placement is that the lesions are still free from metallic implant, therefore leaving the same endovascular and surgical options for restenotic lesions as are available for de novo lesions. Although there are now multiple manufactured DCBs available in the western market which outperformed plain balloon angioplasty in primary patency, much is not yet known about the differences between these DCBs. Each DCB employs a different drug type, drug dose, coating technology, and excipient, and therefore each DCB may have different clinical outcomes. In animal studies, high-dose DCBs demonstrated more effective suppression of intimal hyperplasia [1]. However, there has only been a very limited number of clinical trials conducted which directly compare different types of DCBs. Mori et al. collected data in their LANDMARK registry to compare the 2 year clinical outcomes between low dose Lutonix DCBs (Becton Dickinson and Company, Franklin Lakes, New Jersey) and high-dose IN.PACT DCBs (Medtronic Vascular, Santa Clara, CA, USA) [2]. In the registry, propensity score matching was utilized to minimize the background noise. The outcomes demonstrated that primary patency and freedom from target lesion revascularization were comparable between the two DCBs. No difference was found in the lesions with CTO, TASC-II C/D, or severe calcification. The outcomes were similar to those reported in the COMPARE, randomized controlled study, where comparable rates of primary patency and freedom from major adverse events were demonstrated between IN.PACT DCBs and low dose Ranger DCBs (Boston Scientific, Marlborough, MA, USA) [3].

One large scale prospective study which is currently being conducted in Japan, is the Popcorn registry. The study recruited 3165 limbs where DCB angioplasty was performed for femoropopliteal lesions [4]. In the study, multivariate analysis showed that the usage of Lutonix DCBs presented a 2.4-fold increase in risk of restenosis compared to IN.PACT DCBs. The outcomes were contradictory to the LANDMARK study [4]. The difference between the two registries might have arisen for the following reasons: first, in the LANDMARK registry, the criteria of restenosis included a decrease in 0.20 or more in resting ankle-brachial index (ABI). This criteria cannot exclude the possibility of the cause of the decreased ABI being a de novo lesion without any restenosis. Second, the data from the two registries were not core laboratory adjudicated. Core laboratory assessment of the primary patency by ultrasound specialists adds substantial rigor to the data quality. Third, the selection of DCBs was at the discretion of interventionists in both registries, which might have introduced selection bias. Even though propensity score matching was performed to minimize the background difference in the LANDMARK registry, results should be interpreted with caution. Multiple factors which could have influenced the primary patency were not adjusted for in the registry. For example, the type or size of balloons used for predilatation or true/subintimal wire passage were not adjusted for in this study. Noncompliant balloon, scoring balloon or balloon size for predilatation might have affected the degree of dissection and acute gain after predilatation. The IN.PACT DCB, compatible with a 0.035 wire, might have more often been used after subintimal wire passage. In order to compare the primary patency of the two DCB products by using propensity score matching, these factors need to be adjusted for.

Finally, there was no data as to the safety of the DCBs including rates of mortality and major amputation. After the sensational publication of meta-analysis by Katsanos et al. demonstrating the increased mortality after the usage of paclitaxel devices [5], the US Food and Drug Administration urged caution in their usage. Katsanos et al. also demonstrated that the use of drug-coated balloons increased the risk of major amputations [6]. They also detected a significant dose dependent association between paclitaxel exposure and risk of major amputation/mortality [5, 6]. Although various studies from real world data have shown no significant increase in mortality rates following paclitaxel device usage [7,8,9], the concern has not been fully eliminated. We need to continuously accumulate data to monitor the safety and efficacy of the paclitaxel devices.