Midterm Outcome of Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty versus Drug-Coated Balloon Angioplasty Alone for Femoropopliteal Arteriosclerosis Obliterans.

Journal Pre-proof Midterm Outcome of Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty versus Drug-Coated Balloon Angioplasty Alone for Femoropopliteal Arteriosclerosis Obliterans. Zhiwen Cai, Lianrui Guo, Lixing Qi, Shijun Cui, Zhu Tong, Jianming Guo, Zhonggao Wang, Yongquan Gu PII:

S0890-5096(19)30589-8

DOI:

https://doi.org/10.1016/j.avsg.2019.06.014

Reference:

AVSG 4551

To appear in:

Annals of Vascular Surgery

Received Date: 13 March 2019 Revised Date:

24 May 2019

Accepted Date: 4 June 2019

Please cite this article as: Cai Z, Guo L, Qi L, Cui S, Tong Z, Guo J, Wang Z, Gu Y, Midterm Outcome of Directional Atherectomy Combined with Drug-Coated Balloon Angioplasty versus Drug-Coated Balloon Angioplasty Alone for Femoropopliteal Arteriosclerosis Obliterans., Annals of Vascular Surgery (2019), doi: https://doi.org/10.1016/j.avsg.2019.06.014. This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. © 2019 Published by Elsevier Inc.

1

Midterm Outcome of Directional Atherectomy Combined with Drug-Coated

2

Balloon Angioplasty versus Drug-Coated Balloon Angioplasty Alone for

3

Femoropopliteal Arteriosclerosis Obliterans.

4

Zhiwen Cai, Lianrui Guo, Lixing Qi, Shijun Cui, Zhu Tong, Jianming Guo, Zhonggao

5

Wang, Yongquan Gu*

6

Department of Vascular Surgery, Xuanwu Hospital and Institute of Vascular Surgery,

7

Capital Medical University, Beijing, China

8

ZC: [email protected]; LG: [email protected]; LQ: [email protected]; SC:

9

[email protected]; ZT: [email protected]; JG: [email protected]; ZW:

10 11

[email protected]; YG: [email protected]

*Correspondence: Dr Yongquan Gu [email protected]

12 13

Total word count: 4149.

14 15

Declaration of Conflicting Interests

16

The authors declared no potential conflicts of interest with respect to the research, authorship,

17

and/or publication of this article.

18 19

Acknowledgments

20

This work is supported by the Beijing municipal administration of hospitals clinical technology

21

innovation program [grant number XMLX201610]; the Beijing municipal administration of

22

hospitals climbing talent training program [grant number DFL20150801]; the Beijing outstanding

23

talents project [grant number 2016000020124G108]; the Beijing Municipal Administration of

24

Hospitals Incubating Program [grant number PX2018035], and the Beijing municipal

25

administration of hospitals clinical technology innovation program [grant number XMLX201836].

1

26

Midterm Outcome of Directional Atherectomy Combined with Drug-Coated

27

Balloon Angioplasty versus Drug-Coated Balloon Angioplasty Alone for

28

Femoropopliteal Arteriosclerosis Obliterans.

29 30

Abstract： ：

31

Objective: Compare the therapeutic effects of directional atherectomy combined with drug-coated

32

balloon angioplasty with drug-coated balloon angioplasty alone in the treatment of

33

femoropopliteal arteriosclerosis obliterans.

34

Methods: From June 2016 to June 2018 in our hospital, patients with femoropopliteal

35

arteriosclerosis obliterans received endovascular therapy, they present with life-limiting

36

claudication or severe chronic limb ischemia. The patients were randomized to receive directional

37

atherectomy combined with drug-coated balloon angioplasty (n=45) or drug-coated balloon

38

alone(n=49). 94 patients were enrolled in our study with 72 males and the mean age was 67±10

39

years. The mean lesion length was 112±64 mm.

40

Results: There were no significant differences in the baseline characteristics of patients and lesions

41

between the two randomized groups(P>0.05). Flow-limiting dissections occurred more frequently

42

in the DCB group (n=12; 24.5%) than the DA-DCB group (n=2; 4.4%; P=0.006). The technical

43

success rate in the DA-DCB group was superior to the DCB group (95.6% vs. 75.5%, P=0.006).

44

The mean follow-up was 16.7±6.1 months in the DCB group and 15.3±5.8 months in the

45

DA-DCB group. No amputations were performed. The overall mortality in the DCB group was

46

4.1% (2/49) while all patients survived in the DA-DCB group. The 12-months and 24-months

47

primary patency in the DA-DCB group were greater than the DCB group (80.5% vs. 75.7%, 67.1% 2

48

vs. 55.1%), however using all available patency data, no significant differences over time were

49

observed (P=0.377).

50

Conclusion：In this study, directional atherectomy combined with drug-coated balloon angioplasty

51

can decrease the flow-limiting dissection rate in the treatment of femoropopliteal arteriosclerosis

52

obliterans compared with drug-coated balloon angioplasty alone. There was no significant

53

difference between the two groups in terms of primary patency rate which was needed to be

54

further clarified.

55

Key-words: Directional atherectomy; Drug-coated balloon; Femoropopliteal arteriosclerosis

56

obliterans

57 58 59

Introduction

60

With the improvement of living standards, the change of diet structure and the extension of life

61

expectancy, the incidence of lower limb atherosclerosis shows an obvious rising trend and has

62

become a common and frequently-occurring disease.1 Once, bypass surgery was the first choice to

63

treat lower extremity atherosclerotic occlusion. However, endovascular therapy has the advantages

64

of less trauma, fewer complications and rapid recovery. At present, it has been widely used in

65

clinical practice. Despite the obvious advantages, the application in lesions with high mechanical

66

stress is still a challenge. In femoropopliteal artery disease, the stress of knee joint movement on

67

blood vessels is often related to high restenosis rate, stent fracture and occlusion. As a result, the

68

popliteal artery is considered to be a non-stent area.2 Although the effect of a new generation of

69

stents in this anatomical area has been improved, it has damaged the vascular remodeling and 3

70

interfered with the selection of future surgical methods.

71

The “leave nothing behind” strategies, such as directional atherectomy (DA), drug-coated balloons

72

(DCBs) angioplasty, or combination therapy have been supported by a wide range of vascular

73

surgeons. DA can safely and effectively remove arteriosclerotic plaques, restore blood flow, and

74

reduce the use of stents by physical methods.3

75

DCB carries anti-hyperplasia drugs (such as paclitaxel) on the surface of the balloon. When DCB

76

angioplasty is performed on the target lesions, the vascular intima is dilated and pressurized, and

77

single-dose anti-hyperplasia drugs are temporarily released and transferred to the vascular wall,

78

playing a role in inhibiting intimal hyperplasia and thereby inhibiting restenosis. Many

79

randomized controlled studies have shown that DCBs are superior to uncoated balloons.4-9

80

Atherectomy prior to the use of DCB may have an advantage in decreasing the plaque burden,

81

increasing the size of the lumen, preventing dissection and improving the efficiency of drug

82

delivery into the blood vessel wall. One hypothesis is that DA combined with DCBs not only

83

promotes the entry of anti-proliferative drugs into the vascular wall, improves the uptake of drugs

84

and inhibits intimal hyperplasia, but also inhibits the inflammatory response caused by platelet

85

activation after mechanical injury.10 This prospective study was the first trail in China to compare

86

the therapeutic effects of DA combined with DCBs with DCBs alone in the treatment of

87

femoropopliteal artery stenosis or occlusion.

88

Material and methods

89

Study Design

90

This single center, prospective randomized controlled study, was approved by the local

91

Investigational Review Board. Patients with femoropopliteal arteriosclerosis obliterans received 4

92

percutaneous endovascular surgery in our hospital from June 2016 to June 2018. They suffered

93

from lifestyle-limiting claudication or severe ischemia symptom (rest pain, ulceration or

94

gangrene).

95

Inclusion criteria:(1) all patients signed an informed consent form;(2) digital subtraction

96

angiography (DSA) revealed femoropopliteal artery stenosis ≥70%, or occlusion (3) with

97

unobstructed vascular inflow;(4) with at least a vessel runoff;(5) good compliance and regular

98

follow-up. Exclusion criteria :(1) patients with cerebrovascular diseases less than half a year;(2)

99

arterial

thrombosis;(3)

abnormal

liver

function,

serum

creatinine ＞ 176umol/L;(4)

100

contraindications on paclitaxel, antiplatelet or anticoagulation;(5) abnormal protein C, protein S

101

and antithrombin III;(6) abnormal number of platelets and lower fibrinogen;(7) unsatisfactory

102

control of blood pressure, blood glucose and lipid;(8) unable to quit smoking completely;(9) poor

103

compliance makes regular follow-up impossible.

104

Endovascular Interventions and Medical Care

105

All patients received percutaneous puncture with the Seldinger technique under local anesthesia,

106

and the contralateral femoral artery retrograde puncture or ipsilateral femoral artery anterograde

107

puncture was used to establish the approach.

108

In the DCB group, the stenosis was predilated by uncoated balloon catheters to avoid drug loss,

109

and then was dilated by Orchid paclitaxel-coated peripheral balloon catheters (Acotec Scientific,

110

Beijing, China) at least 180s (the same diameter as the target vessel, 10mm longer than the lesion

111

segment). If flow-limiting dissection or residual stenosis >50% which diagnosed by angiographic

112

examination occurs, an uncoated balloon was used to dilate again (>2min). When the

113

flow-limiting dissections and the rebound (residual stenosis is estimated to be >50%) still exist, 5

114

bailout stents need to be implanted.

115

In the DA-DCB group, SilverHawk or TurboHawk plaque excision system (Medtronic,

116

Minneapolis, MN, USA) was used firstly. All patients who underwent atherectomy were used an

117

embolic protection device (Spider FX; Medtronic, Minneapolis, MN, USA) placed at the distal

118

end of the stenosis vascular, slightly larger than the vessel diameter. Under the guidance of the

119

guidewire, the target lesions were treated with the plaque excision system near-to-far, the

120

debulking speed and angle were controlled. Every time according to the fixed direction, adjust the

121

debulking angle 15 ° - 30 °, 4 to 6 times in total. For every 1-2 times of removal, the plaque debris

122

in the collection tank should be cleaned after exiting the system, so as to avoid falling off to the

123

distal end and causing an embolism. After the removal of the plaques, the lesion site was

124

pre-dilated with an uncoated balloon, and then was treated with DCBs angioplasty. Similarly, an

125

uncoated balloon was used for re-dilation of the flow-limiting dissections(>2min). Bailout stents

126

were used to remedy flow-limiting dissections or rebound vessels (>50%).

127

All patients received aspirin (100mg/d) and clopidogrel (75mg/d) 3 days before surgery. Post

128

procedure, two antiplatelet drugs (aspirin 100mg/d, clopidogrel 75mg/d) were recommended to

129

take orally for 6 months, followed by a long-term oral administration of one antiplatelet drug.

130

Follow-up

131

Patients were evaluated up to hospital discharge, at 30 days, and at 6,12,18,24 months after

132

endovascular interventions. Follow-up visits at each interval included clinical manifestations

133

(claudication distance, relief of rest pain, ulcer healing), physical examination, Rutherford classi-

134

fication and ankle-brachial index (ABI). The vascular ultrasound examinations were performed at

135

6,12,18 and 24 months in our hospital without being aware of which endovascular intervention 6

136

was used. Further DSA should be performed if the vascular ultrasound reveals restenosis >50%.

137

Endpoints and definitions

138

The most important outcome in this study was primary patency rate. Primary patency was defined

139

as no significant restenosis (<50%) or occlusion with no clinically driven reintervention.

140

Significant vascular stenosis (≥50%) was defined as the ratio of blood flow velocity at the

141

systolic stage of the lesion segment to that at the proximal 1cm greater than 2.5 based on color

142

doppler vascular ultrasonography. When patients have clinical symptoms and DSA indicates

143

moderate stenosis at the treatment site (50%-70%) or just DSA indicates severe stenosis (≥70%),

144

they need to receive reintervention whether they have clinical manifestations or not.

145

Secondary outcomes were technical success, limb amputation and any death. Technical success

146

was defined as residual stenosis of the treated vessel <30%, no perforation of the vessel wall, and

147

no embolism at the distal end. Bailout stenting was considered as technical failure.

148

Statistical Analysis

149

SPSS19.0 software was used for data analysis. Continuous variables were presented as means ±

150

standard deviation and compared by means of a paired Student t test, while categorical variables

151

were presented as the counts and compared by means of chi-square test or Fisher’s exact test.

152

Cumulative primary patency rates were estimated using the Kaplan-Meier method. P<0.05 was

153

considered as statistical significance.

154

Results

155

From June 2016 to June 2018, a total of 94 patients were enrolled in this prospective study. 45

156

patients were treated with DA-DCB and 49 with DCB, including 72 males (70.3%) and 22

157

females (29.7%) with an average age of 67 years. The TurboHawk peripheral plaque excision 7

158

system was used in 23 patients and the SilverHawk atherectomy device was applied in the

159

remaining 22. Patient and lesion characteristics are summarized in Table 1. No baseline patient

160

characteristics were statistically significantly different between randomized treatment groups. The

161

majority of lesions were de novo femoropopliteal lesions in both groups. There was no significant

162

difference between the study arms with regards to lesion location, TASC classification, lesion

163

length, reference vessel diameter or vessel runoff.

164

Acute Outcomes

165

No procedure-related adverse events occurred (including hemorrhage, distal embolization,

166

perforation and death) in both groups. In 14 cases (31.1%), debris was collected in the filter basket,

167

no distal embolization occurred. The most common procedural complications were flow-limiting

168

dissections which were treated by bailout stenting. Flow-limiting dissections occurred more

169

frequently in the DCB group (n=12; 24.5%) than in the DA-DCB group (n=2; 4.4%; P=0.006). So

170

technical success rate in the DA-DCB group was superior to the DCB group (95.6% vs. 75.5%,

171

P=0.006). The mean ABI at discharge in the DA-DCB group improved 0.33±0.25 and the DCB

172

group was 0.32±0.25(P=0.847).

173

Follow-up Outcomes

174

The mean follow-up was 16.7±6.1 months in the DCB group and 15.3±5.8 months in the

175

DA-DCB group. No amputations were performed. The overall mortality in the DCB group was

176

4.1% (2/49). One died of cardiac failure at 8 months and another died of unknown causes at 6

177

months. All patients survived in the DA-DCB group. A clinically-driven TLR was performed in

178

two patients who had restenosis in the DCB group. One patient was treated with DCB angioplasty

179

at 9 months, another with a nitinol interwoven stent at 8 months. Two DA-DCB patients received 8

180

DA again after restenosis at 4 months and 1 year respectively.

181

In Figure 1, the primary patency rate at 12 and 24 months, respectively, was 80.5% and 67.1% for

182

the DA-DCB group, 75.7% and 55.1% for the DCB group. Using all available patency data at 12

183

and 24 months, no significant differences over time were observed (generalized estimating

184

equations logistic regression P=0.377).

185

Discussion

186

With the improvement of living standards and aging of the population, the incidence of peripheral

187

atherosclerotic disease is increasing continuously. In 2010, there were about 200 million people

188

with lower limb arteriosclerosis obliterans worldwide, increasing by 23.5% every decade.1

189

Femoropopliteal artery lesions are most common in symptomatic lower limb arteriosclerosis

190

obliterans.11 Exposure of the femoropopliteal artery to high mechanical stress often leads to stent

191

rupture, with the highest risk of postoperative restenosis.12 Currently, endovascular surgery for the

192

treatment of popliteal atherosclerotic occlusion includes uncoated balloon dilatation, stent

193

implantation, freezing balloon, cutting balloon, drug-coated balloon, atherectomy and other

194

surgical methods. The JOINT multi-center trial showed that the patency rate of the

195

femoropopliteal artery after percutaneous endovascular therapy was 76% after one year and 56%

196

after five years13. Rastan et al. found that the 2-year phase patency rate of the popliteal artery

197

lesions treated by Nitinol stent and simple balloon dilation was 64% in the stent group and 31% in

198

the balloon group (P<0.001).14

199

DA is the most commonly used technique for removing atherosclerotic plaques. Physical methods

200

were used to remove plaque and neointima in the lumen, significantly reduced the volume load

201

and avoided early restenosis caused by elastic retraction of the vascular wall.3 It can help restore 9

202

blood flow and reduce the use of stents. In the DEFINITIVE LE study15, the 1-year patency rate

203

for moderate-length popliteal artery lesions (5.0-9.9cm) was 74%, and for long-segment lesions

204

(10cm) was 65%. Some studies have shown that atherectomy has no significant advantages in the

205

perioperative period and long-term improvement of clinical benefits compared with balloon

206

associated with stent implantation.16 It can help to achieve good angiographic success, but has no

207

significant effect on reducing the restenosis rate.17 This reason may be that DA causes damage to

208

the vascular media and deeper layers, which leads to obvious restenosis process and counteracts

209

its advantage in improving vascular compliance.18

210

DCB is a newly emerging percutaneous interventional therapy in recent years. Paclitaxel is

211

currently the most widely used anti-intimal hyperplasia drug in DCBs. The known mechanism is

212

related to the disruption of the microtubule function. After combining with microtubules,

213

paclitaxel inhibits spindle formation and stops cell division, thereby inhibits cell proliferation and

214

generation after interventional therapy.19 On the other hand, paclitaxel can remain in the vascular

215

tissue for a long time. When the balloon expands, with the expansion time reaching 30-60 seconds,

216

paclitaxel can reach the outer membrane of the artery and maintain for several weeks.20 After the

217

single application of DCB, the concentration of paclitaxel in the superficial femoral artery tissue

218

could still be measured at 3-5ng/mg 28 days later.21

219

Many trails have demonstrated the satisfactory effects of using DCBs for femoropopliteal artery

220

lesions.4,6,7,8 There are still two points of concern regarding the use of DCBs: the high risk of

221

flow-limiting dissections increases the usage of bailout stents;22 poor efficacy for calcification

222

lesions.23 There is a great difference in the utilization rate of bailout stent in the reported

223

literature.24 In our study, flow-limiting dissections occurred in 12 patients (24.5%) who received 10

224

DCBs alone, and all of them were treated with bailout stents. In the subgroup analysis of the

225

THUNDER trial25, the non-limiting flow laminae after DCBs did not cause an unsatisfactory

226

effect even without the use of bailout stents, suggesting that a more conservative approach might

227

achieve the same effect. Nevertheless, the primary goal of the "leave nothing behind" strategy is to

228

avoid stent implantation in vessel segments exposed to mechanical stress. Regarding calcified

229

lesions, Tepe et al.6 found that calcified lesions had a higher rate of lumen loss after DCBs therapy,

230

suggesting that plaque resection for vascular preparation could be conducive to the

231

anti-proliferation effect of DCBs.

232

Several trials had been carried out to demonstrate the efficacy of DA combined with DCBs to treat

233

lower limb atherosclerosis disease. Cioppa et al.14 treated heavily calcified femoropopliteal artery

234

lesions with DA combined with DCBs. The mean lesion length was 115mm with a total of 30

235

patients. The rate of bailout stent was 6.5%, and the primary patency rate was 90% after 12

236

months. In a retrospective study by Sixt et al.26, a total of 89 patients with femoropopliteal artery

237

restenosis received DA, including 29 patients in the combined with DCBs group and 60 patients in

238

the combined with uncoated balloon group. Kaplan-Meier survival analysis showed that the 1-year

239

restenosis rate for DCBs was 15.3% while the uncoated balloon group was 56.2%. Multivariate

240

Cox regression analysis of restenosis showed that the risk ratio of DCBs group was 0.28 compared

241

with the uncoated balloon group (0.12-0.66; P=0.0036). The DEFINITIVE AR trial27 compared

242

the treatment of femoropopliteal artery lesions by DA combined with DCBs (DARRT) versus

243

DCBs alone. A total of 102 patients with lifestyle-limiting claudication or rest pain were randomly

244

divided into the DAART group (n=48) and the DCBs group (n=54), with an average lesion length

245

of 11.2±4.0cm and 9.7±4.1 cm. Results showed no statistical difference in either primary patency 11

246

rate (84.6% vs. 81.3%, P=0.78) or freedom from TLR (92.7% vs. 92.0%, P=0.90) at 12 months.

247

Stavroulakis et al.2 reported that from the perspective of primary patency rate, DA combined with

248

DCBs was more advantageous than DCBs alone, but TLR，LLL and other aspects still need to be

249

further proved.

250

In our study, DA combined with DCBs can reduce the incidence of flow-limiting dissections

251

compared with DCBs alone. There was no difference in baseline data between the two random

252

groups. The 12-months and 24-months primary patency in the DA-DCB group were greater than

253

the DCB group (80.5% vs. 75.7%, 67.1% vs. 55.1%), however with no statistical difference

254

(P=0.377). In our opinion, DA causes damage to the vascular media may counteract its advantage

255

in decreasing the plaque burden. On the other hand, the follow-up time was not long enough to

256

show the advantage of combined treatment.

257

Although several trails showed the curative effect of DA combined with DCBs in the treatment of

258

femoropopliteal arteriosclerosis occlusion is satisfactory, some complications still exist. In our

259

study, an embolic protection device was used in each patient (100%) with an embolus capture rate

260

of 31.1%. No distal arterial embolism occurred, significantly protecting the blood flow in vessel

261

runoff. In addition, aneurysm formation limits its wide application. In the DEFINITIVE LE trial17,

262

the overall aneurysm formation rate was 0.5% at 30 days while 0.6% at the TALON trial.28

263

Reducing the damage to the vascular wall can reduce the toxicity of paclitaxel. In any case, it is

264

important to avoid the damage to the vascular outer membrane during DA. The combination of

265

DA and DCBs prolongs the operative time, which is related to the repeatedly replace the catheter

266

and clean the plaque collection tank. The increased dose of repeat angiography and the

267

hospitalization cost is significantly higher than that of DCBs alone. 12

268

Limitations

269

This study was a single-center prospective randomized controlled study. The main shortcoming

270

was the small sample size, and some patients’ follow-up did not reach 24 months. Therefore, it

271

was necessary to expand the sample size and conduct a long-term follow-up.

272

Conclusion

273

DA combined with DCBs in the treatment of femoropopliteal atherosclerotic occlusion has a

274

satisfactory effect, and it can reduce the incidence of flow-limiting dissection. However, there was

275

no significant difference between the two groups in terms of primary patency rate. A multicenter

276

randomized controlled study with a large sample size was needed to further clarify the difference

277

in efficacy between the two surgical methods.

278

Reference

279

1. Fowkes F G, Rudan D, Rudan I, et al. Comparison of global estimates of prevalence and risk

280

factors for peripheral artery disease in 2000 and 2010: a systematic review and analysis[J]. Lancet,

281

2013, 382(9901):1329-40.

282

2. Stavroulakis K, Schwindt A, Torsello G, et al. Directional Atherectomy With Antirestenotic

283

Therapy vs Drug-Coated Balloon Angioplasty Alone for Isolated Popliteal Artery Lesions[J].

284

Journal of Endovascular Therapy, 2016, 24(2): 181-188.

285

3. Yongquan G, Lianrui G, Lixing Q, et al. Plaque excision in the management of lower-limb

286

ischemia of atherosclerosis and in-stent restenosis with the SilverHawk atherectomy catheter. [J].

287

International Angiology, 2013, 32(4):362-7.

288

4. Tepe G, Zeller T, Albrecht T. Local Delivery of Paclitaxel to Inhibit Re-Stenosis During

289

Angioplasty of the Leg[J]. New England Journal of Medicine, 2008, 358(7):689. 13

290

5. Werk M, Albrecht T, Meyer D R, et al. Paclitaxel-coated balloons reduce restenosis after

291

femoro-popliteal angioplasty: evidence from the randomized PACIFIER trial. [J]. Circulation

292

Cardiovascular Interventions, 2015, 5(6):831-840.

293

6. Tepe G, Laird J, Schneider P, et al. Drug-coated balloon versus standard percutaneous

294

transluminal angioplasty for the treatment of superficial femoral and popliteal peripheral artery

295

disease: 12-month results from the IN. PACT SFA randomized trial. [J]. Circulation, 2015,

296

131(5):495.

297

7. Dierk S, Stephan D, Thomas Z, et al. The LEVANT I (Lutonix paclitaxel-coated balloon for the

298

prevention

299

first-in-human randomized trial of low-dose drug-coated balloon versus uncoated balloon

300

angioplasty[J]. Jacc Cardiovascular Interventions, 2014, 7(1):10.

301

8. Rosenfield K, Jaff M R, White C J, et al. Trial of a Paclitaxel-Coated Balloon for

302

Femoropopliteal Artery Disease[J]. New England Journal of Medicine, 2016, 63(3):145-153.

303

9. Fanelli F, Cannavale A, Boatta E, et al. Lower limb multilevel treatment with drug-eluting

304

balloons: 6-month results from the DEBELLUM randomized trial[J]. Journal of Endovascular

305

Therapy An Official Journal of the International Society of Endovascular Specialists, 2012,

306

19(5):571.

307

10. Beschorner U, Zeller T. Combination of mechanical atherectomy and drug-eluting balloons for

308

femoropopliteal in-stent restenosis. [J]. Journal of Cardiovascular Surgery, 2014, 55(3):347-9.

309

11. Kasapis C, Gurm HS. Current approach to the diagnosis and treatment of femoral-popliteal

310

arterial disease. A systematic review. Curr Cardiol Rev 2009; 5:296–311.

311

12. Cioppa A, Stabile E, Popusoi G, et al. Combined treatment of heavy calcified femoro-popliteal

of

femoropopliteal

restenosis)

trial

14

for

femoropopliteal

revascularization:

312

lesions using directional atherectomy and a paclitaxel coated balloon: One-year single centre

313

clinical results. [J]. Cardiovascular revascularization medicine: including molecular interventions,

314

1900, 13(4):219-23.

315

13. Soga Y, Tomoi Y, Sato K, et al. Clinical outcome after endovascular treatment for isolated

316

common femoral and popliteal artery disease. Cardiovasc Interv Ther. 2013; 28:250–257.

317

14. Rastan A, Krankenberg H, Baumgartner I, et al. Stent placement vs. balloon angioplasty for

318

popliteal artery treatment: two-year results of a prospective, multicenter, randomized trial. J

319

Endovasc Ther. 2015; 22:22–27.

320

15. McKinsey JF, Zeller T, Rocha-Singh KJ, et al. Lower extremity revascularization using

321

directional atherectomy 12-month prospective results of the DEFINITIVE LE study. JACC

322

Cardiovasc Interv. 2014; 7:923–933.

323

16. Diamantopoulos A, Katsanos K. Atherectomy of the femoropopliteal artery: a systematic

324

review and meta-analysis of randomized controlled trials. [J]. Journal of Cardiovascular Surgery,

325

2014, 55(5):655-65.

326

17. Zeller T, Krankenberg H, Steinkamp H, et al. One-Year Outcome of Percutaneous Rotational

327

Atherectomy With Aspiration in Infrainguinal Peripheral Arterial Occlusive Disease: The

328

Multicenter Pathway PVD Trial[J]. Pflügers Archiv, 2009, 334(1):39-49.

329

18. Shammas N W. Commentary: The Adluminal Origin of Restenosis in Peripheral Artery

330

Interventions and Its Implications for the Development of Future Treatment Strategies: Searching

331

Deep into the Arterial Wall[J]. Journal of Endovascular Therapy, 2015, 22(5):716-718.

332

19. Axel D I, Kunert W, Göggelmann C, et al. Paclitaxel Inhibits Arterial Smooth Muscle Cell

333

Proliferation and Migration In Vitro and In Vivo Using Local Drug Delivery[J]. Circulation, 1997, 15

334

96(2):636.

335

20. Schmidt A, Piorkowski M, Werner M, et al. First experience with drug-eluting balloons in

336

infrapopliteal arteries: restenosis rate and clinical outcome. [J]. Journal of the American College of

337

Cardiology, 2011, 58(11):1105-1109.

338

21. Tellez A, Dattilo R, Mustapha J A, et al. Biological effect of orbital atherectomy and

339

adjunctive paclitaxel-coated balloon therapy on vascular healing and drug retention: early

340

experimental insights into the familial hypercholesterolaemic swine model of femoral artery

341

stenosis. [J]. Eurointervention Journal of Europcr in Collaboration with the Working Group on

342

Interventional Cardiology of the European Society of Cardiology, 2014, 10(8):1002.

343

22. Cortese B, Granada JF, Scheller B, et al. Drug-coated balloon treatment for lower extremity

344

vascular disease intervention: an international positioning document. Eur Heart J. 2016; 37:1096–

345

1103.

346

23. Tepe G, Beschorner U, Ruether C, et al. Drug-eluting balloon therapy for femoropopliteal

347

occlusive disease: predictors of outcome with a special emphasis on calcium. J Endovasc Ther.

348

2015; 22:727–733.

349

24. Laird JR, Schneider PA, Tepe G, et al. Durability of treatment effect using a drug-coated

350

balloon for femoropopliteal lesions: 24-month results of IN. PACT SFA. J Am Coll Cardiol. 2015;

351

66:2329–2338.

352

25. Tepe G, Zeller T, Schnorr B, et al. High-grade, non-flow-limiting dissections do not negatively

353

impact long- term outcome after paclitaxel-coated balloon angioplasty: an additional analysis from

354

the THUNDER study. J Endovasc Ther.2013;20:792–800.

355

26. Sixt S, Cancino O G C, Treszl A, et al. Drug-coated balloon angioplasty after directional 16

356

atherectomy improves outcome in restenotic femoropopliteal arteries[J]. Journal of Vascular

357

Surgery, 2013, 58(3):682.

358

27. Zeller T, Langhoff R, Rocha-Singh K J, et al. Directional Atherectomy Followed by a

359

Paclitaxel-Coated Balloon to Inhibit Restenosis and Maintain Vessel Patency: Twelve-Month

360

Results of the DEFINITIVE AR Study[J]. Circulation Cardiovascular Interventions, 2017, 10(9).

361

28. Ramaiah V, Gammon R, Kiesz S, et al. Midterm outcomes from the TALON Registry: treating

362

peripherals with SilverHawk: outcomes collection. J Endovasc Ther.2006;13:592–602.

17

Table 1. Baseline characteristics of patients and lesions Characteristics

DCB(n=49)

DA-DCB(n=45)

P

67±11

0.943

Age，y

67±9

Men (%)

35(71.4)

37(82.2)

0.217

Smoker (%)

24(49.0)

23(51.1)

0.836

Hypertension (%)

41(83.7)

31(68.9)

0.091

Diabetes mellitus (%)

32(65.3)

24(53.3)

0.237

Coronary artery disease (%)

14(28.6)

18(40.0)

0.243

Hyperlipidemia (%)

33(67.3)

28(62.2)

0.603

Chronic kidney disease (%)

3(6.1)

4(8.9)

0.907

Cerebrovascular disease (%)

11(22.4)

10(22.2)

0.979

Rutherford category (%)

0.478

3

32(58.3)

34(37.5)

4

9(16.7)

7(20.0)

5

8(8.3)

4(10.0)

Ankle-brachial index

0.56±0.26

0.61±0.26

Lesion location (%)

0.389 0.799

SFA

33(67.3)

30(66.7)

Popliteal

1(2.1)

2(4.4)

Both

15(30.6)

13(28.9)

Lesion type (%)

1.000

De novo

47(95.9)

43(95.6)

Restenosis

2(4.1)

2(4.4)

TASC II classification (%)

0.902

A

7(14.3)

7(15.6)

B

17(34.7)

18(40.0)

C

23(46.9)

19(42.2)

D

2(4.1)

1(2.2)

Lesion length，mm

111±63

113±66

0.914

Reference vessel diameter，mm

4.9±0.6

5.1±0.5

0.062 0.856

Vessel runoff (%) 1

18(36.7)

19(42.2)

2

15(30.6)

13(28.9)

3

16(32.7)

13(28.9)

DA: Directional atherectomy. DCB: Drug-coated balloon. SFA: Superficial femoral artery.

Figure 1. Kaplan-Meier curves showing total primary patency