3-year results of ZEPHYR (ZilvEr PTX for the Femoral ArterY and Proximal Popliteal ArteRy) registry

Transcription

1 3-year results of ZEPHYR (ZilvEr PTX for the Femoral ArterY and Proximal Popliteal ArteRy) registry (no. UMIN ) Osamu Iida, MD FACC 1 ; Mitsuyoshi Takahara, MD, PhD 2 ; Yoshimitsu Soga, MD 3 ; Masatsugu Nakano, MD, PhD 4 ; Yasutaka Yamauchi, MD, PhD 5 ; Kan Zen, MD, PhD 6 ; Daizo Kawasaki, MD, PhD 7 ; Shinsuke Nanto MD, PhD, FACC 8 ; Hiroyoshi Yokoi, MD 9 ; and Masaaki Uematsu, MD, PhD, FACC 1, on behalf of the ZEPHYR investigators. 1 Cardiovascular Center, Kansai Rosai Hospital; 2 Department of Metabolic Medicine, Osaka University Graduate School of Medicine; 3 Department of Cardiology, Kokura Memorial Hospital; 4 Division of Cardiology, Saiseikai Yokohama-City Eastern Hospital; 5 Cardiovascular Center, Kikuna Memorial Hospital; 6 Department of Cardiovascular Medicine, Omihachiman Community Medical Center; 7 Cardiovascular Division, Department of Internal Medicine, Morinomiya Hospital; 8 Department of Advanced Cardiovascular Therapeutics, Osaka University Graduate School of Medicine; 9 Cardiovascular Center, Fukuoka Sanno Hospital

2 DISCLOSURE Conflict of interest: None Funding Source: General Incorporated Association Japan Endovascular Treatment (JET) Conference, New-Hamamatsu Building, Hamamatsucho, Minato-ku, Tokyo , Japan. Disclosures: Dr. Nanto has received grant support from Terumo, Japan.

3 BACKGROUND Zilver paclitaxel-eluting stent (PTX), a recently developed drug-eluting stent (DES), has shown superior long-term outcomes for femoropopliteal (FP) lesions relative to percutaneous transluminal angioplasty (PTA) and provisional bare metal stent (BMS) in clinical trials. Primary patency@2 years Primary Zilver PTX (DES) : 74.8% PTA with provisional BMS: 57.3% Optimal PTA: 53.4% PTA: 26.5% Dake MD, et al. J Am Coll Cardiol 2013;61:

4 Real-world Outcomes Remain Unknown However, the population in these trials seems less severe than a real-world population in clinical practice. To date, real-world outcomes of Zilver-PTX implantation for FP lesions including challenging ones remain to be systematically studied. Population in clinical trials Population in clinical practice Type A Type B Type C Type D

5 1-year incidence rate One-year results of ZEPHYR study (1) n=690 Age 73.6±8.8 Diabetes mellitus 69% 50% 40% Hemodialysis 30% CLI 32% CTO 45% 30% 20% Restenosis 24% ISR 15% 10% Lesion length (cm) 17±10 Calcification 65% 0% MALE Restenosis One-year incidence of restenosis was estimated to be 37%, while 1-year MALE was observed in 22%, indicating that MALE accounted for 58% in lesions with restenosis. Iida O, et al. JACC Cardiovasc Interv. 2015;8:

6 1-year incidence One-year results of ZEPHYR study (2) 1) lesion length 16 cm 2) EEM area 27 mm 2 60% 50% 40% 30% 20% 10% 3) MSA 12 mm 2 0% MALE 0 (n = 146) Restenosis 1 (n = 192) Number of risk factors 2-3 (n = 231) 1-year restenosis rate was as low as 15% in cases with none of these risk factors, whereas it reached 51% in those with 2 risk factors. Iida O, et al. JACC Cardiovasc Interv. 2015;8:

7 OBJECTIVE To investigate whether these three risk factors for oneyear restenosis would still have a predictive impact on longer-term restenosis risk.

8 METHODS study design The original ZEPHYR study was a prospective multicenter observational study, enrolling FP lesions of symptomatic PAD patients treated with Zilver-PTX. Collection of 3-year follow-up data is now in progress. The original study enrolled 831 lesions in 797 limbs of 690 patients Both pre- and post-ivus data are available in 569 lesions in 546 limbs of 486 patients 3-year follow-up data are already collected and therefore currently available in 187 lesions in 184 limbs of 169 patients 3-year follow-up data in the other cases are now collecting

9 METHODS outcome & statistical analysis Outcome measures Primary endpoint Secondary endpoint Study endpoints 3-year restenosis with a tolerance of ± 2 months Major adverse limb event (MALE) Definition Assessed by DUS* (peak systolic velocity ratio > 2.4) or by angiography ( 50% diameter stenosis) *DUS: duplex ultrasonography Major amputation or any reintervention, including both surgical or endovascular reintervention Statistical analysis For calculating the restenosis rate, MALE was counted as restenosis: Restenosis rate = P MALE + (1 P MALE ) P Restenosis *P MALE : MALE rate in the overall population, *P restenosis : Restenosis rate in MALE-free subgroup 95% CIs were estimated by 100,000-time bootstrap resampling. Statistical analysis was performed by R version (R Core Team).

10 RESULTS BACKGROUND CHARACTERISTICS of cases with pre- and post-ivus data available Patient characteristics (n = 486) Age (years) 74 ± 8 Male sex 354 (73%) Body mass index (kg/m 2 ) 22.3 ± 3.3 Hypertension 416 (86%) Hyperlipidemia 347 (71%) Diabetes mellitus 335 (69%) Hemodialysis 137 (28%) History of smoking, past/current 228 (47%) / 100 (21%) Coronary artery disease 238 (49%) Cerebrovascular disease 85 (17%) Number of antiplatelet agents 2.2 ± 0.5 Data were from the original database.

11 RESULTS Lower limb characteristics (n = 546) Critical limb ischemia 152 (28%) Lesion characteristics (n = 569) Chronic total occlusion 243 (43%) Restenosis 130 (23%) Lesion length (cm) 16 ± 10 Calcification 337 (59%) IVUS-evaluated distal EEM area (mm 2 ) 28 ± 10 IVUS-evaluated MSA (mm 2 ) 15 ± 4 Data were from the original database.

12 3-year incidence of restenosis & MALE 60% 50% 40% 30% 20% 10% MALE Restenosis 0% 1 yr 2 yr 3 yr The 1- and 3-year restenosis rate was 36% [28 43%] and 51% [42 60%], respectively, indicating that the majority (70% [58 81%]) of 3-year restenosis occurred during the first one year. (n = 187, whose 3-year follow-up data are currently available.)

13 Primary patency rate Risk stratification Risk factor 1) lesion length 16 cm, 2) EEM area 27 mm 2, 3) MSA 12 mm 2 100% 80% 0 factor 74% [56-89%] 60% 40% 20% 1 factor 2 factors 57% [43-70%] 29% [16-43%] odds ratio 2 fold odds ratio 7 fold 0% 0 yr 1yr 2 yr 3 yr (n = 187, whose 3-year follow-up data are currently available.)

14 SUMMARY The current study investigated 3-year real-world outcomes of Zilver-PTX treatment for FP lesions in clinical practice. During 3-year follow-up, restenosis occurred in around a half of cases, whereas MALE occurred in one third. Risk factors for 1-year restenosis, i.e., Lesion length 16cm, EEM area 27mm 2, and MSA 12 mm 2, were predictive for 3-year restenosis risk.

15 CONCLUSION The ZEPHYR registry demonstrated real-world 3-year outcomes after Zilver-PTX implantation for FP lesions, including challenging cases. Lesion length, distal EEM area and MSA were independent predictors for restenosis.

16 Acknowledgments Kansai Rosai Hospital Osamu Iida, Kiyonori Nanto, Masaaki Uematsu Kokura Memorial Hospital Yoshimitsu Soga, Yusuke Tomoi Saiseikai Yokohama-City Eastern Hospital Keisuke Hirano, Masatsugu Nakano Kikuna Memorial Hospital Yasutaka Yamauchi Omihachiman Community Medical Center Kan Zen Shin-Koga Hospital Yoshiaki Shintani Yamagata University School of Medicine Hiroki Takahashi Hyogo College of Medicine Masashi Fukunaga, Kojiro Miki Kanazawa Medical University Hospital Taketsugu Tsuchiya Sendai Kousei Hospital Kenji Suzuki, Akiko Tanaka Japanese Red Cross Fukuoka Hospital Nobuhiro Suematsu, Shunji Hayashidani Graduate School of Medicine, Kyoto University Takeshi Kimura, Junichi Tazaki Matsuyama Red Cross Hospital Terutoshi Yamaoka Tokyo Rosai Hospital Makoto Utsunomiya Sanda City Hospital Daisuke Ogasawara JA Hokkaido Engaru Kosei General Hospital Takahide Suzuki Shinshu University Graduate School of Medicine Yusuke Miyashita Fukuyama City Hospital Yoichiro Naito, Kenzo Kagawa, Makoto Nakahama Hikone Municipal Hospital Tsuyoshi Miyazawa Kobe Rosai Hospital Kyozo Inoue Japanese Red Cross Kyoto Daini Hospital Yoshinori Tsubakimoto Morinomiya Hospital Daizo Kawasaki Tokai University School of Medicine Norihiko Shinozaki Sakakibara Heart Institute Michiaki Higashitani Asahikawa Medical University Nobuyoshi Azuma, Atsuhiro Koya Kawakita General Hospital Atsushi Tosaka Osaka University Graduate School of Medicine Mitsuyoshi Takahara Fukuoka Sanno Hospital Hiroyoshi Yokoi Nishinomiya Hospital Affairs, Nishinomiya Municipal Central Hospital Shinsuke Nanto JET Administrative Office Kaori Shimogama ZEPHYR Secretariat, N. Practice, Co.,Ltd. Noriko Fujii

17 3-year results of ZEPHYR (ZilvEr PTX for the Femoral ArterY and Proximal Popliteal ArteRy) registry (no. UMIN ) Osamu Iida, MD FACC 1 ; Mitsuyoshi Takahara, MD, PhD 2 ; Yoshimitsu Soga, MD 3 ; Masatsugu Nakano, MD, PhD 4 ; Yasutaka Yamauchi, MD, PhD 5 ; Kan Zen, MD, PhD 6 ; Daizo Kawasaki, MD, PhD 7 ; Shinsuke Nanto MD, PhD, FACC 8 ; Hiroyoshi Yokoi, MD 9 ; and Masaaki Uematsu, MD, PhD, FACC 1, on behalf of the ZEPHYR investigators. 1 Cardiovascular Center, Kansai Rosai Hospital; 2 Department of Metabolic Medicine, Osaka University Graduate School of Medicine; 3 Department of Cardiology, Kokura Memorial Hospital; 4 Division of Cardiology, Saiseikai Yokohama-City Eastern Hospital; 5 Cardiovascular Center, Kikuna Memorial Hospital; 6 Department of Cardiovascular Medicine, Omihachiman Community Medical Center; 7 Cardiovascular Division, Department of Internal Medicine, Morinomiya Hospital; 8 Department of Advanced Cardiovascular Therapeutics, Osaka University Graduate School of Medicine; 9 Cardiovascular Center, Fukuoka Sanno Hospital