Disclosures Advisory committee: Boston Scientific, Medtronic, - PDF document

4/8/19 Gender Related Differences in Peripheral Artery Disease Outcomes Maureen P. Kohi, MD, FSIR Associate Professor of Clinical Radiology Chief, Interventional Radiology University of California, San Francisco Disclosures • Advisory committee: Boston Scientific, Medtronic, Philips • Consulting: Medtronic, Cook, Boston Scientific, Bard, Philips 1

4/8/19 Women are not 70 kg men 2

4/8/19 Must be Hormones… Hirsch AT et al. Circulation 2012;125:1449-72 3

4/8/19 Different Comorbidities for PAD Traditional risk factors Women-specific or or comorbidities “Novel” comorbidities • Diabetes mellitus • Depression • Cigarette smoking • Hypothyroidism • Advanced age • Arthritis • Dyslipidemia • Osteoporosis • Hypertension • Inflammation Grenon SM et al. J Vasc Surg 2014; 60: 396-403 Barochiner J et al. Vasc Health Risk Manag 2014;10:115-28 Different Presentation of PAD for Women • More likely to be older – Postmenopausal state lacks the atheroprotective effects of hormones – Symptoms go unnoticed or mistaken for other diseases – Less likely to present with intermittent claudication – More likely to live alone and socially isolated • More likely to present with advanced disease – Chronic limb ischemia – More femoropopliteal and multi-level infrainguinal disease • Have poor lower extremity strength and greater functional impairment McCoach CE et al. Vasc Med 2013;18:19-26 Vouyouka AG et al. J Vasc Surg 2010;52:1196-202 4

4/8/19 Treatments & Outcomes POBA DCB • Outcomes from a multisite 12-month follow-up data set from the Excellence in Peripheral Artery Disease (XLPAD) registry – 898 patients, 50% women • Propensity score method used to balance sample sizes and baseline characteristics between genders • No difference in mortality rate • Women had higher 12-month reintervention rate Jeon-Slaughter H et al. Am J Cardiol 2017; 119:490-6 5

4/8/19 • Meta-analysis with 10 articles comprised a sample size of 1,292 patients • Rate of TLR in DCB-treated patients was significantly lower compared with patients treated with PTA at 6 months (odds ratio [OR], 0.24; 95% confidence interval [CI], 0.11-0.53; P<.0004), 12 months (OR, 0.28; 95% CI, 0.13-0.62; P<.002), and 24 months (OR, 0.25; 95% CI, 0.10-0.61; P<.002) • Decreased late lumen loss and binary restenosis was demonstrated at 6 months in patients treated with DCBs compared with patients treated with PTA (mean difference, 0.74; 95% CI, 0.97 to 0.51; <.00001; OR, 0.34; 95% CI, 0.23-0.49; P< .00001) • CONCLUSIONS: Treatment with DCBs compared with PTA results in reduced rates of reintervention in patients with PAD J Vasc Surg 2017;65:558-70 6

4/8/19 Women are not 70 kg men • Conclusions: The reduced TLR rate following DCB treatment was maintained over the 5-year follow up period • LLL at 6-month follow up – Men: 0.42 mm DCBs vs. 1.76mm PTA – Women: 0.37mm DCBs vs. 1.61mm PTA • TLR at 5-years follow up – Men: 17% DCBs vs. 71% PTA – Women: 38% DCBs vs. 52% PTA Tepe G et al. JACC 2015;8:102-8 7

4/8/19 • CONCLUSIONS: DCB are safe and effective in delaying rather than preventing restenosis in long, complex lesions and restenosis of the femoropopliteal tract Schmidt A et al. JACC Cardiovasc Interv 2016;9:715-24 • At 12 months, the rate of primary patency among patients who had undergone angioplasty with the drug-coated balloon was superior to that among patients who had undergone conventional angioplasty (65.2% vs. 52.6%, P = 0.02) • The proportion of patients free from primary safety events was 83.9% with the drug- coated balloon and 79.0% with standard angioplasty (P = 0.005 for noninferiority) • There were no significant between-group differences in functional outcomes or in the rates of death, amputation, thrombosis, or reintervention • CONCLUSIONS: Among patients with symptomatic femoropopliteal peripheral artery disease, percutaneous transluminal angioplasty with a paclitaxel-coated balloon resulted in a rate of primary patency at 12 months that was higher than the rate with angioplasty with a standard balloon. The drug-coated balloon was noninferior to the standard balloon with respect to safety Rosenfield K et al. N Engl J Med 2015;373:145-53 8

4/8/19 http://www.fda.gov/downloads/AdvisoryCommittees/CommitteesMeetingMaterials/MedicalDevices/MedicalDevicesAdvisoryCommittee/ CirculatorySystemDevicesPanel/UCM400614.pdf Thieme M et al. JACC Cardiovasc Interv 2017 Aug 28;10(16):1682-1690 9

4/8/19 • Primary patency remained significantly higher among patients treated with DCB compared with PTA (69.5% versus 45.1%; P<0.001) • The rates of clinically driven target lesion revascularization were 15.2% and 31.1% (P=0.002) for the DCB and PTA groups, respectively • Functional outcomes were similarly improved between treatment groups even though subjects in the DCB group required significantly fewer reinterventions versus those in the PTA group (P<0.001 for target lesion revascularization, P=0.001 for target vessel revascularization) • There were no device or procedure-related deaths • CONCLUSIONS: Durable and superior treatment effect among patients treated with DCB versus standard PTA, with significantly higher primary patency and lower clinically driven target lesion revascularization, resulting in similar functional improvements with reduced need for repeat interventions Schneider PA et al. Circ Cardiovasc Interv 2018;11(1):e005891 IN.PACT SFA Trial Primary Patency at 3-years 2 Dr. Kohi, LINC 2018 10

4/8/19 IN.PACT SFA Trial Primary Patency through 3 Years Females performed as well as males 1 Dr. Kohi, LINC 2018 IN.PACT SFA Trial Freedom from CD-TLR through 3 Years Females performed as well as males 1 Dr. Kohi, LINC 2018 11

4/8/19 • Primary patency rate was significantly higher with DCB (76.3% for DCB versus 57.6% for PTA, P =0.003) • Rate of clinically driven target lesion revascularization was significantly lower in the DCB cohort (7.9% versus 16.8%, P =0.023) • Improvements in ankle-brachial index, Rutherford class, and quality of life were comparable, but the PTA cohort required twice as many revascularizations • CONCLUSIONS: The data demonstrate superior safety and effectiveness of the Stellarex DCB in comparison with PTA, and plasma levels of paclitaxel fall to low levels within 1 hour Krishnan P et al. Circulation 2017;136:1102-1113 Stellarex Results 12 month 12 month Primary Patency CD-TLR P = 0.48 P = 0.078 100% 100% 81.7% 78.8% 75% 75% 50% 50% 9.9% 25% 25% 5.2% 0% 0% male female male female Maureen Kohi, MD 12

4/8/19 • Primary patency rate was higher in males than females (84.5% vs.72.8%, P value=0.015) • Rate of freedom from CD-TLR was 96.2% in males and 90.7% in females (P value=0.0370) • Angiographic core lab geographic miss was higher in females (18.4% of cases) versus 11.6% in males P=0.067) Schroë H et al. Catheter Cardiovasc Interv 2018;91(3):497-504 13

4/8/19 Why is there a Gender Gap?? • Lack of awareness – “Women don’t get atherosclerotic disease!” • Higher reintervention rate at long term follow up for women • Several data points have demonstrated worse outcomes for women following DCBs when compared to men, yet other trials have demonstrated no differences • There may exist a potential platform difference • We need a larger data set in order to determine the role of DCBs in the treatment and management of women with PAD 14

4/8/19 This is NOT our Patient Population! This is… 15

4/8/19 Thank you! maureen.kohi@ucsf.edu 16