論文ID: CJ-25-0087
Background: This study compared procedural complications, patency, and adverse events between a stent strategy and drug-coated balloon (DCB) treatment after using the JETSTREAM atherectomy device for severely calcified femoropopliteal (FP) lesions.
Methods and Results: We retrospectively analyzed multicenter data from 588 patients who underwent endovascular therapy for severely calcified de novo FP lesions between April 2018 and December 2023 at 8 centers in Japan. Patients were categorized into 2 groups based on the revascularization method: stent strategy and DCB after JETSTREAM atherectomy. Propensity score matching (PSM) was performed to compare primary patency, clinically driven target lesion revascularization (CD-TLR), and the occurrence of acute limb ischemia (ALI)/major amputation at 1 year. After PSM, 82 matched pairs of patients were identified, with no significant intergroup differences in baseline characteristics. The rates of primary patency, CD-TLR, ALI, and major amputation were similar between the 2 groups. However, the rate of distal embolization was significantly higher in the DCB after JETSTREAM group. (18.3% vs. 1.2%; P<0.001) Baseline characteristics had no interaction effects on the association between the 2 strategies and the 1-year restenosis risk.
Conclusions: DCB after JETSTREAM atherectomy demonstrated comparable safety, except for distal embolization, and high efficacy in patients with severely calcified FP lesions, suggesting that it may be an alternative revascularization method to the stent strategy.
Catheter intervention for femoropopliteal (FP) artery lesions with severe calcification presents challenges, such as difficulties in wire passage, device passage, and balloon dilation failure. However, recent advances in catheter devices and improved techniques for managing calcification have gradually mitigated these issues.1–3 When treated with the latest stents, calcification is no longer identified as a predictor of restenosis.4–6 A multicenter study in Japan reported that drug-coated balloon (DCB) treatment for FP lesions is less effective for severely calcified lesions and is associated with restenosis as a prognostic factor.7 In response, the JETSTREAM atherectomy device (Boston Scientific, Marlborough, MA, USA) has been approved for use in Japan in 2023 and is now available for routine clinical practice. Clinical trial data shows that when a DCB is deployed after using the JETSTREAM atherectomy device for severely calcified FP lesions, the primary patency rate at 6 months is 96.7%, indicating favorable treatment outcomes.8 However, these trials involved relatively simple patient and lesion characteristics, and it remains unclear whether these results are applicable in real-world clinical settings. If the DCB-after-JETSTREAM strategy proves to be effective for treating severely calcified FP lesions in clinical practice, clinicians may face a dilemma in choosing between JETSTREAM- and stent-based strategies. If the JETSTREAM-based strategy demonstrates efficiency comparable to that of stent-based treatment, then FP lesions can be treated with a DCB, preserving future revascularization options in case of restenosis. However, no comparative study has assessed these 2 strategies in this patient population. Therefore, the aim of the present study was to evaluate the safety and efficiency of JETSTREAM-based treatment for FP lesions with severe calcification compared with a stent-based approach.
We retrospectively reviewed the medical records of patients with FP lesions who underwent revascularization with endovascular therapy (EVT) at 8 cardiovascular centers in Japan between January 2018 and December 2023. This study was designed as a multicenter retrospective chart review study.
The inclusion criteria were age ≥20 years, symptomatic lower limb ischemia with atherosclerotic lesions, de novo lesions, and severely calcified lesions. The exclusion criteria were non-atherosclerotic lesions, mid-to-distal popliteal lesions, and contralateral lesions in the same patient.
In all, 588 consecutive patients (588 lesions) with severely calcified FP who underwent revascularization with EVT were included in the study. Patients were categorized into 2 groups based on the revascularization method, namely those treated with a stent strategy and those treated with a DCB after JETSTREAM atherectomy. A 1 : 1 propensity score matching (PSM) analysis was performed to adjust for differences in baseline, lesion, and procedural characteristics.
Clinical follow-up evaluations were performed up to 12 months, using ankle-brachial index (ABI) measurements, duplex ultrasound, computed tomography, or angiography. Follow-up data were obtained from hospital records or by contacting the patients, family members, or referring physicians. A study flowchart is shown in Figure 1.
Study flowchart. DCB, drug-coated balloon; LEAD, lower extremity artery disease; PACSS, peripheral artery calcification scoring system.
The study was conducted in accordance with the principles of the Declaration of Helsinki. The study protocol was approved by the Nagoya Heart Center (Reference no. NHC2023-0821-03), in addition to the ethics committees or institutional review boards of the participating centers. Given the retrospective nature of the study, the requirement for written informed consent from patients was waived.
InterventionEVT was performed at the discretion of the treating physician, who selected either the stent strategy or DCB after JETSTREAM atherectomy. All procedures were performed under local anesthesia, with intravenous anesthesia administered as needed, depending on institutional protocols. Depending on the complexity of the lesion and aortoiliac artery tortuosity, either an ipsilateral antegrade or contralateral crossover approach was chosen. For the ipsilateral antegrade approach, a 6-Fr sheath, 6-Fr Destination (Terumo, Tokyo, Japan), or 6-Fr patent sheath (Medikit, Tokyo, Japan) was introduced through the ipsilateral common femoral artery. For the contralateral crossover approach, a 6-Fr Destination, 6-Fr patent sheath, or 6-Fr sheathless PV (Asahi Intec, Aichi, Japan) was inserted via the contralateral femoral artery. When using the JETSTREAM atherectomy device, a 7-Fr sheath was required instead of a 6-Fr sheath. After sheath insertion, unfractionated heparin was administered to achieve an activated clotting time of >250 s. A 0.014-/0.018-/0.035-inch guidewire was used depending on lesion characteristics and physician preference. A retrograde approach was used when necessary. In the stent strategy group, the following stents were used as final devices: Zilver PTX stent (Cook Medical, Bloomington, IN, USA); Eluvia stent (Boston Scientific, Marlborough, MA, USA); S.M.A.R.T stent (Cordis Endovascular, Warren, NJ, USA); Supera stent (Abbott, Chicago, IL, USA); and VIABAHN stent (W.L. Gore & Associates, Newark, DE, USA). For the group with a DCB after the use of the JETSTREAM atherectomy device, the following DCBs were used as final devices: IN.Pact (Medtronic, Dublin, Ireland); Ranger (Boston Scientific, Marlborough, MA, USA); and Lutonix (BARD, Tempe, AZ, USA). The specific method of JETSTREAM atherectomy was left to the discretion of the attending physician.
Antiplatelet therapy with aspirin (100 mg daily), clopidogrel (75 mg daily), prasugrel (3.75 mg daily), or cilostazol (100 mg twice daily) was started at least 1 week before EVT. Therapy was continued for at least 1 month after the placement of bare-metal stents and for at least 3 months after the placement of drug-coated and drug-eluting stents. At least 1 antiplatelet drug was maintained after EVT in all patients. In patients with comorbidities, such as atrial fibrillation, direct oral anticoagulants or warfarin were used in combination.
EndpointsThe primary endpoints of the study were procedural complications, primary patency, clinically driven target lesion revascularization (CD-TLR), and the occurrence of acute limb ischemia (ALI) or major amputation at 1 year.
DefinitionsProcedural success was defined as a residual stenosis of <30% without a suboptimal result. Severely calcified lesions were classified using the peripheral artery calcification scoring system Grades 3–4, which categorize lesion calcification severity based on angiographic findings.9 Chronic limb-threatening ischemia (CLTI) included heterogeneous conditions with varying degrees of ischemia that may delay wound healing and increase amputation risk.10 Procedural complications included access-site bleeding, pseudoaneurysm, transfusion, vessel perforation, and distal embolization. Primary patency was defined as the absence of restenosis in the treated vessel or the need for revascularization. Restenosis was defined as either a peak systolic velocity ratio >2.4; >50% stenosis on angiography, duplex ultrasound, or computed tomography; or a decrease of 0.2 in the resting ABI.11 CD-TLR was defined as repeat EVT for a target lesion exhibiting >50% stenosis at follow-up. Major amputation was defined as amputation above the ankle.
Statistical AnalysisBaseline characteristics are presented as the mean±SD for continuous variables and as frequency (percentage) for categorical variables. The significance of differences in baseline characteristics was assessed using the Chi-squared test or Fisher’s exact test for categorical variables and the t-test or Mann-Whitney U test for continuous variables. To minimize intergroup differences, the propensity score was calculated using a multivariate logistic regression model with the strategy (stent strategy vs. DCB after JETSTREAM atherectomy) as the dependent variable. All baseline characteristics, including age, sex, body mass index, ambulatory status, Rutherford classification, hypertension, diabetes, dyslipidemia, hemodialysis, chronic kidney disease, coronary artery disease, cerebral vascular disease, atrial fibrillation, current smoking, preprocedural ABI, popliteal lesion, chronic total occlusions (CTO), reference diameter, lesion length, number of runoffs, and the use of adjunctive devices (intravascular ultrasound, scoring balloon, cutting balloon, high-pressure balloon) were included as covariates. Matching was performed using the logic of the propensity score. A caliper cut-off of 0.20 was used to obtain a satisfactory balance.12 Primary patency, CD-TLR, and ALI/major amputation rates were compared using the Kaplan-Meier method, followed by the log-rank test after PSM.
P<0.05 (two-tailed) was considered statistically significant. All statistical analyses were performed using JMP version 14.0.2 (SAS Institute Inc., Cary, NC, USA).
Before PSM, 467 patients were treated with the stent strategy and 121 were treated with a DCB after using the JETSTREAM atherectomy device. After PSM, 82 matched patient pairs were identified for the analysis. Baseline patient, lesion, and procedural characteristics are summarized in Tables 1 and 2, respectively. Before matching, several significant differences were observed in patient and lesion characteristics, with the stent strategy group being older (74.9 vs. 72.8 years; P=0.02), having a lower percentage of men (68.7% vs. 77.7%, P=0.05), ambulatory patients (78.4% vs. 94.2%, P<0.001), patients with coronary artery disease (49.7% vs. 65.3%, P=0.002), current smokers (15.9% vs. 57.9%, P<0.001), intravascular ultrasound use (78.8% vs. 95.9%, P<0.001), and the use of scoring/cutting balloons (25.5% vs. 43.0%, P<0.001), a lower ABI (0.48 vs. 0.58; P=0.001), a higher prevalence of CTO (43.7% vs. 24.0%; P<0.001), and larger (6.01 vs. 5.77 mm; P=0.001) and longer (182 vs. 155 mm; P=0.009) lesions that the DCB after JETSTREAM group. After PSM, there were no significant differences in baseline patient, lesion, and procedural characteristics between the 2 groups.
Baseline Characteristics Before and After PSM
| Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|
| Stent | DCB+JETSTREAM | P value | Stent | DCB+JETSTREAM | P value | |
| No. patients | 467 | 121 | 82 | 82 | ||
| Age (years) | 74.9±9.1 | 72.8±8.7 | 0.02 | 72.9±8.7 | 73.1±8.9 | 0.88 |
| Male sex | 321 (68.7) | 94 (77.7) | 0.05 | 61 (74.4) | 58 (70.7) | 0.60 |
| BMI (kg/m2) | 24.5±3.6 | 22.6±3.3 | 0.06 | 23.5±4.1 | 22.8±3.6 | 0.24 |
| Ambulatory | 366 (78.4) | 114 (94.2) | <0.001 | 77 (93.9) | 76 (92.7) | 0.75 |
| Rutherford class | ||||||
| 2 | 51 (10.9) | 21 (17.4) | <0.001 | 15 (18.3) | 14 (17.1) | 0.99 |
| 3 | 187 (40.0) | 67 (55.4) | 40 (48.8) | 43 (53.4) | ||
| 4 | 39 (8.4) | 10 (8.3) | 5 (6.1) | 5 (6.1) | ||
| 5 | 159 (34.1) | 17 (14.1) | 18 (22.0) | 16 (19.5) | ||
| 6 | 31 (6.6) | 6 (5.0) | 4 (4.9) | 4 (4.9) | ||
| Hypertension | 394 (84.4) | 105 (86.8) | 0.50 | 74 (90.2) | 72 (87.8) | 0.62 |
| Diabetes | 334 (71.5) | 82 (67.8) | 0.42 | 60 (73.2) | 54 (65.9) | 0.31 |
| Dyslipidemia | 270 (57.8) | 81 (66.9) | 0.07 | 55 (67.1) | 54 (65.9) | 0.87 |
| Hemodialysis | 266 (57.0) | 64 (52.9) | 0.42 | 37 (45.1) | 38 (46.3) | 0.88 |
| CKD | 124 (30.0) | 35 (28.9) | 0.83 | 33 (40.2) | 25 (30.5) | 0.19 |
| Coronary artery disease | 232 (49.7) | 79 (65.3) | 0.002 | 51 (62.2) | 47 (57.3) | 0.52 |
| Cerebrovascular disease | 78 (16.7) | 15 (12.4) | 0.24 | 9 (11.0) | 12 (14.6) | 0.48 |
| Current smoker | 74 (15.9) | 70 (57.9) | <0.001 | 36 (43.9) | 35 (42.7) | 0.87 |
| Atrial fibrillation | 71 (15.2) | 18 (14.9) | 0.93 | 14 (16.9) | 10 (12.1) | 0.38 |
Unless indicated otherwise, data are given as the mean±SD or n (%). BMI, body mass index; CKD, chronic kidney disease; DCB, drug-coated balloon; PSM, propensity score matching.
Lesion and Procedural Characteristics Before and After PSM
| Before PSM | After PSM | |||||
|---|---|---|---|---|---|---|
| Stent | DCB+JETSTREAM | P value | Stent | DCB+JETSTREAM | P value | |
| No. patients | 467 | 121 | 82 | 82 | ||
| Preprocedural ABI | 0.48±0.29 | 0.58±0.32 | 0.001 | 0.53±0.28 | 0.55±0.34 | 0.69 |
| Popliteal lesion | 205 (43.9) | 58 (47.9) | 0.43 | 42 (51.2) | 39 (47.6) | 0.76 |
| Chronic total occlusion | 204 (43.7) | 29 (24.0) | <0.001 | 22 (26.8) | 23 (28.1) | 0.86 |
| Reference diameter (mm) | 6.01±0.77 | 5.77±0.58 | 0.001 | 5.80±0.68 | 5.81±0.56 | 0.93 |
| Lesion length (mm) | 181.9±103.4 | 154.6±93.6 | 0.009 | 164.7±96.9 | 166.1±99.7 | 0.92 |
| Runoff | ||||||
| No runoff | 30 (6.4) | 6 (5.0) | 0.007 | 5 (6.1) | 3 (3.7) | 0.88 |
| 1 | 198 (42.4) | 36 (29.8) | 29 (35.4) | 28 (34.2) | ||
| 2 | 183 (39.2) | 51 (42.2) | 32 (39.0) | 35 (42.7) | ||
| 3 | 56 (12.0) | 28 (23.1) | 16 (19.5) | 16 (19.5) | ||
| IVUS | 368 (78.8) | 116 (95.9) | <0.001 | 76 (92.7) | 77 (93.9) | 0.75 |
| Scoring/cutting balloon | 119 (25.5) | 52 (43.0) | <0.001 | 28 (34.2) | 31 (37.8) | 0.63 |
| High-pressure balloon | 384 (82.2) | 93 (76.9) | 0.19 | 68 (82.9) | 63 (76.8) | 0.33 |
| Stent type | NA | NA | ||||
| Eluvia | 222 (47.5) | – | 40 (48.8) | – | ||
| Zilver PTX | 6 (1.3) | – | 1 (1.2) | – | ||
| S.M.A.R.T. | 83 (17.8) | – | 7 (8.5) | – | ||
| Supera | 137 (29.3) | – | 33 (40.2) | – | ||
| Viabahn | 19 (4.1) | – | 1 (1.2) | – | ||
| DCB type | NA | NA | ||||
| IN.PACT Admiral | – | 31 (25.6) | – | 21 (25.6) | ||
| Ranger | – | 87 (71.9) | – | 59 (72.0) | ||
| Lutonix | – | 3 (2.5) | – | 2 (2.4) | ||
| Distal protection device | – | 64 (52.9) | – | 37 (45.1) | ||
Unless indicated otherwise, data are given as the mean±SD or n (%). ABI, ankle-brachial index; IVUS, intravascular ultrasound. Other abbreviations as in Table 1.
Post-procedural ABI and complications rates, except for distal embolization during a procedure, were similar between the 2 groups (Table 3). Distal embolization was significantly more frequent in the DCB after JETSTREAM atherectomy group. (18.3% vs. 1.2%; P<0.001), but was successfully managed in all cases. The 1-year primary patency rate was 87.2% in the stent strategy group and 91.6% in the DCB after JETSTREAM atherectomy group, with no significant difference between the 2 groups (Figure 2A). Moreover, there were no significant differences between the 2 groups in terms of CD-TLR and the rate of ALI/major amputation at 1 year (Figures 2B,3).
Intervention Results
| Stent | DCB+JETSTREAM | P value | |
|---|---|---|---|
| No. patients | 82 | 82 | |
| Postprocedural ABI | 0.97±0.21 | 0.96±0.17 | 0.81 |
| Access site bleeding/pseudoaneurysm | 1 (1.2) | 1 (1.2) | 1.0 |
| Transfusion | 1 (1.2) | 2 (2.4) | 0.56 |
| Vessel perforation | 1 (1.2) | 1 (1.2) | 1.0 |
| Distal embolization | 1 (1.2) | 15 (18.3) | <0.001 |
Unless indicated otherwise, data are given as the mean±SD or n (%). Abbreviations as in Tables 1,2.
Kaplan-Meier curves for (A) primary patency and (B) freedom from clinically driven target lesion revascularization (CD-TLR) in the groups treated with a stent strategy or a drug-coated balloon (DCB) after the JETSTREAM atherectomy device for severely calcified femoropopliteal lesions.
Kaplan-Meier curves for (A) acute limb ischemia (ALI) and (B) major amputation in the groups treated with a stent strategy or a drug-coated balloon (DCB) after the JETSTREAM atherectomy device for severely calcified femoropopliteal lesions.
As shown in Figure 4, there were no statistically significant interaction effects between different variables and the restenosis risk in the 2 treatment strategy groups (P for interaction>0.05).
Forest plot showing the hazard ratios (HRs) for the association between treatment strategy (stent vs. drug-coated balloon after JETSTREAM) and restenosis risk in different subgroups. No significant interaction effects were found. CLTI, chronic limb-threatening ischemia.
Two key findings emerged from the present study. First, there were no significant differences in the rates of primary patency and freedom from CD-TLR at 1 year between the stent and DCB after JETSTREAM atherectomy groups. Second, for FP lesions with severe calcification, there was no difference in safety between the 2 treatment strategies, except for distal embolization.
To date, no study has evaluated the effectiveness of the JETSTREAM atherectomy device in treating FP lesions with severe calcification, which is commonly encountered in clinical practice in Japan. In clinical trials of the safety and efficacy of rotational atherectomy in patients with peripheral arterial disease with FP lesions in Japan, 22.6% of patients were on dialysis and 32.3% had CTO, with a lesion length of 122 mm.8 In the present study, after PSM, approximately 30% of patients had CTO and approximately 45% of patients were on dialysis, whereas the mean lesion length was 165 mm, presenting a complex lesion background. Despite this, the primary patency rate was approximately 90%, indicating a favorable patency outcome. Studies of rotational atherectomy from overseas have reported freedom from CD-TLR rates at 1 year for the same complex lesions of 88.0–92.6%,13–15 which is comparable to the rates observed in the present study.
However, recent advances in stent technology, specifically the introduction of the Eluvia stent, have improved patency rates. According to the CAPSICUM (contemporary outcomes after paclitaxel-eluting peripheral stent implantation for symptomatic lower limb ischemia with superficial femoral or proximal popliteal lesion) study, calcification was not identified as a prognostic factor for restenosis.5 In addition, the use of the Supera stent for severe calcified FP lesions has been considered, but the BURDOCK (best endovascular therapy for calcified femoropopliteal artery disease with interwoven nitinol stent backup strategy) study report did not identify calcification as a predictor of restenosis.6
These findings suggest that calcification is not a prognostic factor of restenosis and that a stent-based treatment strategy may be sufficient. However, restenosis and re-occlusion can still occur as a result of other factors. Re-occlusion after stent placement is associated with poor prognosis, and the presence of stents limits treatment options, making it preferable to avoid unnecessary stent placement in initial treatments.16 Among patients being treated with the stent strategy in the present study, the most commonly used stent was the Eluvia stent. Notably, endoscopic findings suggest that the Eluvia stent has a thrombotic predisposition, raising concerns about potential stent occlusion.17
The strategy of using a DCB after JETSTREAM atherectomy has been considered as an alternative to stent placement. However, there have been no direct comparisons with stent-based treatments. Therefore, we conducted a comparative analysis in the present study. Because this was a retrospective study with differences in patient and lesion characteristics, analysis was performed after PSM. As expected, there were no significant differences in patency rates and CD-TLR between the 2 groups, suggesting that both treatments are useful for FP lesions with severe calcification in terms of patency. A previous study reported that there was no difference in the efficacy and safety between the DCB or stent strategy in patients with CLTI.18
One concern when using the JETSTREAM atherectomy device is the increased risk of perioperative complications. Previous international reports have indicated complication rates of 0–11%.8,13–15,19 In the present study, the complication rate, except for distal embolization, in the JETSTREAM group was approximately 5%, which was comparable to the rate in the stent group. However, distal embolization occurred more frequently in the JETSTREAM group, highlighting the need for preventive interventions, such as distal protection or other appropriate measures. For example, one study reported that filters significantly reduce distal embolism, making them a viable option.20 In the present study, distal protection was used in approximately half the patients, but its use should be considered in all patients to prevent distal embolization. If this complication can be mitigated with appropriate prevention, DCB after JETSTREAM atherectomy could be considered an alternative to stent-based treatment. In Japan, only the JETSTREAM atherectomy device is currently available, but international reports suggest that a directional atherectomy device is also useful for FP lesions with severe calcification.21 A recent report comparing directional atherectomy and excimer laser atherectomy showed 1-year patency rates of 88% and 81%, respectively, indicating favorable outcomes.22 In addition, intravascular lithotripsy has demonstrated sufficient lesion dilation in cases of severe calcification, with a reported 1-year patency rate of 80%.23,24 These devices, if approved for use in Japan in the future, may be alternative treatment options to stent therapy.
Future studies are needed to directly compare the outcomes of a JETSTREAM atherectomy device with those of other atherectomy devices, as well as with traditional stent-based treatment.
In summary, there were no significant differences in primary patency, freedom from CD-TLR at 1 year, or perioperative complications (except for distal embolization) between stent-based treatment and DCB after JETSTREAM atherectomy for FP lesions with severe calcification. However, this study was a retrospective study with a follow-up period of only 1 year. Therefore, further prospective trials with longer follow-up periods are necessary to fully evaluate the long-term outcomes and potential advantages of atherectomy devices compared with stents.
Study LimitationsThis study has some important limitations. First, the number of patients was small because of PSM to overcome baseline differences between the 2 groups. Second, the study was retrospective and was not conducted in a core laboratory. Finally, the study cohort was limited to Japanese patients. Further prospective studies are warranted to confirm our findings in other populations.
DCB deployment after using a JETSTREAM atherectomy device showed comparable safety, except for distal embolization, and high efficacy in patients with severely calcified FP lesions, suggesting that it may be an alternative revascularization method to the stent strategy.
None.
This study did not receive specific fundings.
T.N. is a consultant for Asahi Intecc., BD, Boston Scientific, COOK Medical, Cordis, Kaneka Medix, NIPRO, and OrbusNeich. All other authors report that they have no relationships relevant to the content of this paper.
This study was approved by the Nagoya Heart Center (Reference no. NHC2023-0821-03), in addition to the ethics committees or institutional review boards of the other participating centers.
The deidentified participant data will not be shared.
