ACC NY Cardiovascular Symposium

Transcription

1 ACC NY Cardiovascular Symposium Peripheral Vascular Disease: Watch the Heart and the Brain Evolving Role of Exercise, ACE-Inhibitors, Interventional and Surgical Options Mark A. Creager, M.D President, American Heart Association Dartmouth-Hitchcock Heart and Vascular Center Geisel School of Medicine at Dartmouth Lebanon, NH

2 None Conflicts of Interest

3 Peripheral Artery Disease (PAD) The presence of a stenosis or occlusion in the aorta or arteries of the limbs Usually caused by atherosclerosis Associated with an increased risk of death, myocardial infarction, and stroke May impair walking or cause critical limb ischemia

4 Global Prevalence of PAD The global burden of PAD is estimated to be 202 million persons The prevalence increases with age In HIC, the prevalence of PAD is similar between women and men In LMIC, the prevalence of PAD was higher in women than men at most ages Fowkes FG, et al. Lancet. 2013;382(9901): Estimated Age-Specific PAD Prevalence for Women and Men in HIC and LMIC Age, Women, % Men, % years HIC LMIC HIC LMIC

5 The German Epidemiological Trial on ABI Study: Event-free Survival by PAD status Diehm, C. et al. Circulation 2009;120:

6 Percent REACH Registry One Year Event Rates for the Composite of CV Death, MI and Stroke The REACH Registry recruited >68,000 outpatients aged 45 years with established CV disease or 3 risk factors from 44 countries CAD PAD CVD Risk Factors CAD CVD PAD Risk Factors Approximately 25% of the patients with PAD had a history of MI, 30% had angina, 16% had a previous stroke, and 15% had a previous TIA Steg PG et al,. JAMA 2007;297(11):

7 Contemporary PAD Outcomes in Germany n = 41,882 PAD patients hospitalized during Followed until 2013, (mean 1144 days) 7,825 patients were amputated and 10,880 died. Death Amputation Reinecke et al. Eur Heart J 2015;36:

8 Physican Use of Secondary Prevention Therapies in PAD Statin use 18.7% 57.5% PAD with CVD PAD without CVD ACE/ARB use 20.8% 34.3% p<0.0001* Anti-platelet therapy use 27.4% 65.8% * Statistical comparison by Chi-square test 0 20% 40% 60% 80% Pande et al., Circulation, 2011

9 Existing disease The Efficacy of Statin Therapy The Heart Protection Study Incidence of events Statin Control (n=10,269) (n=10,267) Previous MI Other CHD No prior CHD or CBV disease PAD Diabetes All patients Risk vs Control Statin favored Placebo 24% Reduction (P<.0001) Heart Protection Study Collaborative Group. Lancet. 2002;360:7-22.

10 REACH Registry: Statin Therapy and Adverse Limb Outcomes in Patients with PAD Multivariate modeling Statin use (Y/N) (N = 5,861) Multivariate modeling Time-varying statin use (N = 5,006) Multivariate modeling Propensity analysis (N = 5,642) All-cause mortality 0.82 ( ) P= ( ) P= ( ) P=0.51 CV mortality 0.83 ( ) P= ( ) P= ( ) P=0.21 Non-fatal MI 0.89 ( ) P= ( ) P= ( ) P=0.004 Non-fatal stroke Non-fatal stroke 0.73 ( ) P= ( ) P= ( ) P= ( ) P= ( ) P= ( ) P=0.006 Worsening claudication or Worsening claudication or new CLI new CLI 0.82 ( ) P= ( ) P= ( ) P= ( ) P= ( ) P= ( ) P= New limb revascularization 0.83 ( ) P= ( ) P= ( ) P= New limb revascularization 0.83 ( ) P= ( ) P= ( ) P= New New amputation amputation (0.48 ( ) 0.86) P= P= (0.44 ( ) 0.82) P= P= (0.43 ( ) 0.74) P< P< Days from Randomization Kumbhani D J et al. Eur Heart J 2014

11 Atorvastatin in Patients With Claudication and PAD Mean change from baseline in PFWT (sec) mg 80 mg Placebo PFWT=pain-free walking time. *P=.03. No change in ABI over 12 months. Mohler ER et al. Circulation. 2003;108: Baseline Month 3 Month 6 Month 12 *

12 ACE Inhibitors in PAD The HOPE Trial No. of Patients History of CAD 7477 No history of CAD 1820 Prior MI 4892 No prior MI 4405 CBV disease 1013 No CBV disease 8284 Peripheral vascular disease 4051 No peripheral vascular disease 5246 Microalbuminuria 1956 No microalbuminuria 7341 Relative risk in ramipril group Reduced Increased HOPE Study Investigators. N Engl J Med. 2000;342:

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14 CHARISMA: Affect of Clopidogrel plus Aspirin vs. Aspirin Alone on MI, Stroke, or CV Death Population RRR (95% CI) P Qualifying CAD, CVD, or PAD 0.88 (0.77, 0.998).046 (n=12,153) Multiple risk factors 1.20 (0.91, 1.59).20 (n=3,284) Overall population* (0.83, 1.05).22 (N=15,603) Clopidogrel better Placebo better Bhatt DL, Fox KA, Hacke W, et al. New England Journal of Medicine, 2006

15 CHARISMA: Outcomes in the PAD Cohort P Cacoub et al., Euopean Heart Jounal, 2009

16 TIMI TRA2 o P: Effect of Vorapaxar on CV Events in PAD Event Rate 14% 12% 10% 8% 6% 4% 2% CV Death, MI, or Stroke N = 3767 Placebo Vorapaxar Hazard Ratio 0.94; 95% CI ( ) p = % 11.3% 0% Days from Randomization Morrow DA, Braunwald E, Bonaca MP. N Engl J Med. 2012; 366:

17 Event Rate (%) 5 5% 4% 4 3% 3 2% 2 1% 1 0% Effect of Vorapaxar on Limb Vascular Events in PAD Hospitalization for Acute Limb Ischemia Pre-specified, adjudicated N = 3767 Placebo Vorapaxar Hazard Ratio % CI 0.39 to 0.86 p = Bonaca et al Circulation. 2013;127: Days from randomization 3.9% 2.3%

18 Effect of Vorapaxar on Limb Vascular Events 25% 25 20% 20 15% 15 Event Rate (%) 10% 10 Peripheral Revascularization Prespecified N = 3767 Placebo Vorapaxar 22.2% 18.4% 5% 5 Hazard Ratio 0.84; 95% CI 0.73 to 0.97 p = % Days from randomization Bonaca et al Circulation. 2013;127:

19 Treatment of Symptomatic PAD Medical Therapy Exercise Training Revascularization Endovascular Intervention vs. Open Surgical Revscularizartion

20 Effect of Cilostazol on Maximal Walking Distance: A Meta-analysis Nine randomized, placebo controlled trials Percent Mean Change from Baseline in Maximal Walking Distance * * Cilostazol 100 mg Cilostazol 50 mg Placebo Pentoxifylline Pande et al., Vasc Med : 181

21 Claudication: Exercise vs. Endoluminal Revascularization The CLEVER Study Peak Walking Time Change from Baseline to Six (6) Months minutes Minutes n = 22 n = 43 n = 46 Pair-Wise Comparisons Difference (minutes) P Value Exercise vs. OMC 4.6 (95% CI, ) <0.001 Stenting vs. OMC 2.5 (95% CI, ) 0.02 Exercise vs. Stenting 2.1 (95% CI, ) 0.04 TP Murphy et al., Circulation, Published online

22 The ERASE Trial Endovascular Revascularization and Supervised Exercise vs. Supervised Exercise for Intermittent Claudication Fahkry et al., JAMA. 2015;314(18):

23 The IRONIC Trial: Improved Walking Distance with an Invasive vs. Noninvasive Strategy n =158 Nordanstig J et al. Circulation. 2014;130:

24 The IRONIC Trial: Improved Quality of Life with an Invasive Strategy Nordanstig J et al. Circulation. 2014;130:

25 The BASIL Study Angioplasty vs Bypass Surgery on Amputation Free Survival in Patients with CLI BASIL Trial Participants, Lancet, 366:1925, 2005

26 NHLBI-sponsored prospective, randomized, multicenter, open label superiority trial 2,100 patients at 120 clinical sites in United States and Canada 4-year trial extending from , with each patient having minimum of 2 year follow-up

27 Thank you!