Disclosures Medical management and Research Funding from Novartis - PowerPoint PPT Presentation

4/7/2017 Disclosures Medical management and • Research Funding from Novartis exercise – Current state of the • Funding from NHLBI/PCORI to study evidence in claudication interventions to improve functioning in PAD Mary M. McDermott, MD Jeremiah Stamler Professor of Medicine Northwestern University Feinberg School of Medicine April 7, 2017 Statin Therapies to Reduce Therapeutic Goals for PAD Cardiovascular Risk • Reduce cardiovascular events – Statins • Statin medication is indicated for all – Smoking cessation patients with PAD to reduce – Anti-platelet therapy cardiovascular risk – Blood pressure control • Statins reduce risk of cardiovascular • Increase pain-free walking distances events by about 25% – Supervised exercise – Revascularization – Medications 1

4/7/2017 Statin Therapies to Reduce Smoking Cessation Cardiovascular Risk in PAD • Patients with PAD who smoke cigarettes • Potent statins recommended at highest or use other tobacco forms must be tolerated dose advised at every visit to quit smoking – Atorvastatin – Rosuvastatin • Develop a plan that includes – Simvastatin pharmacotherapy • Generally safe and often well tolerated – Varenicline – Bupropion – Nicotine replacement therapy • Refer to a smoking cessation program Anti-platelet therapy to Vorapaxar reduce cardiovascular events • Novel anti-platelet agent • Aspirin(75 to 325 mgs) or clopidogrel (75 mgs) • Antagonist of protease-activated receptor-1 (PAR-1) • Evidence does not support combined • PAR-1 receptors exist on aspirin + clopidogrel to prevent CVD – Platelets (activation) events in PAD – Vascular endothelium • Role of vorapaxar added to existing anti- – Smooth muscle platelet therapy for people with PAD is unclear 2

4/7/2017 Anti-coagulation to prevent Vorapaxar cardiovascular events • No effect on cardiovascular event rates in people with PAD • Anti-coagulation is not indicated to reduce • Reduced rates of acute limb ischemia and cardiovascular events in patients with PAD. lower extremity revascularization rates in PAD • Associated with increased risk (bleeding) Circulation. 2013;CIRCULATIONAHA.112.000679, originally published March 15, 2013 Anti-Hypertensive Therapy • Anti-hypertensive therapy should be Medical Management to administered to people with PAD and HTN to Improve walking ability in PAD reduce risk of cardiovascular events. • ACE Inhibitors and ARBs may be particularly patients with claudication effective in preventing cardiovascular events in PAD. 3

4/7/2017 Cilostazol and Pentoxifylline Cilostazol for PAD • Phosphodiesterase type 3 inhibitor • Vasodilator • Anti-platelet properties • Provides modest benefit- about 40% improvement in treadmill walking • Side effects common – Headache, palpitations, diarrhea, Gerhard-Herman, et al. Circulation. 2016;CIR.0000000000000470 lightheadedness Mean Change in Maximal Walking Distance Supervised Treadmill Exercise in Response to Supervised Exercise for PAD Interventions 2012 meta-analysis • 25 Randomized Clinical Trials • Supervised treadmill exercise vs. control • 1,054 patients with claudication • Program length: 4-104 weeks Fakhry F et al, J Vasc Surg 2012;56:1132-1142. Fakhry F et al, J Vasc Surg 2012;56:1132-1142. 4

4/7/2017 Characteristics of More Effective 2017 Proposed Decision Supervised Walking Exercise Programs Memorandum from CMS in PAD • “Evidence is sufficient to provide coverage for • Exercise Frequency: > 3 times weekly. patients with symptoms of intermittent • Exercise duration: > 30 minutes per session. claudication to treat peripheral artery disease.” • Walking to maximal claudication pain may be best. • Program duration of at least six months. What is needed to implement CMS coverage of supervised exercise for claudication supervised treadmill exercise for claudication • 12-week sessions • Additional 36 sessions may be obtained with • Treadmill for exercise training justification – Treadmills starting at 0.50 miles per hour • Three sessions/week • Exercise physiologist or RN • Hospital or out-patient hospital setting • Delivered by qualified personnel with basic and • Cardiac rehabilitation programs can advanced cardiac life support training and training administer supervised exercise to PAD in exercise for PAD patients • Must take place under direct supervision of a • Cardiac stress test prior to exercise physician 5

4/7/2017 Summary: Prescription for Supervised Supervised Treadmill Exercise Treadmill Exercise • Three times weekly exercise • Supervised treadmill exercise improves • Start with 15 minutes of walking time per treadmill walking performance in PAD session • Improvement is observed 4-12 weeks after • Increase walking time each week by 5 onset of exercise minutes • Goal is 45 to 60 minutes of treadmill walking • Even with medical insurance, attendance per session three times weekly can be a challenge 2016 Clinical Practice Guidelines 12-week home-based exercise for Home-based exercise for PAD program in PAD • 180 participants. • Practice Guidelines: Class IIA, Level of • Randomized to supervised treadmill exercise, Evidence A home-based walking exercise, or control. • Home based exercise is reasonable to • 12 week home-based walking exercise prescribe to improve walking performance in intervention PAD. – Three days walking per week. – Medical center visits once monthly – Step-counter used to provide feedback . Gardner AW et al, J Am Heart Assoc 2014;3:e001107 6

4/7/2017 Change in peak treadmill walking Home based exercise improves six minute time by supervised vs. home-based walk distance more than supervised exercise exercise P <0.05 vs. control Overall P value < P <0.05 vs. supervised Overall P value = 0.028* Change in peak walking time 0.001* P <0.05 vs. control 6MWT total distance (m) P <0.05 vs. control (seconds) Gardner AW et al, J Am Heart Assoc 2014;3:e001107. Gardner AW et al, J Am Heart Assoc 2014;3:e001107. Summary: How to Implement Home-Based Home-based walking exercise Exercise in PAD • Advise participants to walk for exercise at • Growing evidence suggests that home- least three –preferably 4/5 days per week based exercise has benefit for PAD • Start with 10-15 minutes per session of • Successful programs incorporate behavioral exercise change strategies • Increase walk time by 5 minutes each week • Set goals • Effective programs have patients return to • Monitor progress the medical center at least once monthly for • Activity monitor may help feedback 7

4/7/2017 Home-based exercise: Summary: Exercise for PAD Additional considerations • Walking exercise is effective for patients • Successful home-based programs require with PAD behavioral change interventions – Supervised • Requires more self-motivation – Home-based • Not as easy to ‘prescribe’ • CMS coverage likely coming soon for • Improves over ground walking more than supervised exercise supervised treadmill exercise • Home-based therapies require behavioral • Benefits may be more durable than change techniques supervised exercise – Important long-term therapeutic option SILC Trial: Changes in 6 minute walk performance by group among PAD Strength Training in PAD participants with and without intermittent claudication • Improves treadmill walking in PAD ǂ P-value<0.001 Change in 6-minute walk (Meters) • Not as effective as walking exercise 20 15 • Improves quality of life and patient 10 perceived walking * P-value = 0.33 5 0 -5 -10 -15 -20 Diet Strength Treadmill N=42 N=47 N=42 * Pair-wise P-value (diet vs. strength); ǂ Pair-wise P-value (diet vs. treadmill) McDermott MM et al, JAMA 2009;301:165-174. McDermott MM et al, JAMA 2009;301:165-174. 8

4/7/2017 SILC Results: Change in treadmill walking performance among PAD participants with and without claudication Change in Performance (Meters) Upper and Lower Extremity 250 ǂ P-value<0.0001 200 Ergometry Exercise in PAD * P-value = 0.001 150 100 50 0 Diet Strength Treadmill N=39 N=41 N=45 Total treadmill walking distance * Pair-wise P-value (diet vs. strength); ǂ ǂ Pair-wise P-value (diet vs. treadmill) ǂ ǂ McDermott MM et al, JAMA 2009;301:165-174. Ergometry improves maximum walking Randomized Controlled Trial: Upper distance in PAD patients with Limb Ergometry in Peripheral Arterial claudication (N=104) Disease Patients • 104 patients with PAD Statistical significance: • Randomized: * P < .05; ** P < .01: – to upper-limb aerobic ergometry exercise indicates significantly higher than control – lower limb aerobic ergometry exercise patients; – control •†† P < .01: indicates • 24 week follow-up significantly higher than baseline – Outcomes measured every six weeks • Primary outcomes: – Absolute walking distance – Time to onset of claudication Zwierska I et al, J Vasc Surg 2005;42:1122-1130. Zwierska I et al, J Vasc Surg 2005;42:1122-1130. 9