Dott. Marco De Carlo Cardiothoracic and Vascular Dept . University of Pisa - Italy

1. 18th EUROCHAP EuropeanChapterCongress of the International UnionofAngiology XIX MLAVS 2009 Annual Meeting of the Mediterranean League ofAngiology and VascularSurgery After CARP and COURAGE Studies:Should we screen patients with PAD for asymptomatic coronary disease? Dott. Marco De Carlo Cardiothoracic and VascularDept. Universityof Pisa - Italy

2. Vascularcomorbidity >60 years Ness J. J Am Geriatr Soc 1999;47:1255-6

3. PAD: impact on prognosis 3649 subjects (average age, 64 yrs) followed-up for 7.2 years % Hooi JD. J ClinEpid 2004;57:294–300

4. Non-cardiacsurgery Perioperative risk of death/MI 30-day risk of cardiac death or myocardial infarction Poldermans D. Eur Heart J 2009 Aug 27 [Epub] 

5. The carp trial McFalls EO. NEJM 2004;351:2795-804

6. CARP: aim • To assess the benefit of prophylactic coronary artery revascularizationbefore major vascular surgery in patients at increased risk for perioperative cardiac complications and with clinically stable, angiographically significant coronary artery disease McFalls EO. NEJM 2004;351:2795-804

7. Carp: Patientpopulation • Allpatientsscheduledforvascularsurgerywerescreened • Patientscouldbeenrolledif: • judged at high riskofcardiaccomplications • had >70% coronarystenosis at angiography • wereamenableto PCI or CABG McFalls EO. NEJM 2004;351:2795-804

8. CARP: Enrollment Only 8.7% of 5859 screenedpatientswereenrolled!

9. CARP: Patientallocationand treatment No revasc 7.0% revasc 3.6% McFalls EO. NEJM 2004;351:2795-804

10. CARP: Patient profile VariableRevasc No Revasc P Value (N=258) (N=252) Age, yr 65.6±11.1 67.2±10.4 0.10 Previous MI (%) 111 (43.0) 103 (40.9) 0.62 Previous CHF (%) 31 (12.0) 19 (7.5) 0.09 Previous CVA (%) 54 (20.9) 47 (18.7) 0.50 Diabetes (%) 97(37.6) 101(40.0) 0.84 Current smoker (%) 128 (49.6) 114 (45.2) 0.41 Leftventricular EF % 54±12 55±12 0.36 3V disease (%) 91 (35.3) 79 (31.3) 0.69 Previous CABG (%) 38 (14.7) 39 (15.5) 0.83 McFalls EO. NEJM 2004;351:2795-804

11. Carp: results McFalls EO. NEJM 2004;351:2795-804

12. CARP: subgroup analysis § The criteria include ≥3 among: age >70, angina, Q waves on ECG, previous CHF, previous ventricular tachycardia, or diabetes mellitus

13. Carp: conclusions • Coronary artery revascularization before elective vascular surgery does not significantly alter the long-term outcome • Thus, among patients with stable cardiac symptoms, preventive coronary artery revascularization cannot be recommended

14. CarpstudyLimitations • Only 8.7% ofscreenedpatientswereenrolled • Cardiacriskstratificationwasnotuniform • Only 32% of the enrolledpatientshad 3-vessel disease • CHF rate wasalmostdouble in “Revasc” arm • Relevant crossover betweenrandomizationarms • Complete revascwith PCI in 61.9%; no useof DES • Periproceduralmortalityof PCI was 1.4% • 3.9% mortalityafteruncomplicated CABG or PCI beforevascularsurgery

15. Carp: stratification on coronary angiography Garcia S. Am J Cardiol 2008;102:809-13

16. Carp: stratification on coronary angiography Survival 2.5 years after vascular surgery Garcia S. Am J Cardiol 2008;102:809-13

17. Carp: stratification on coronary angiography Garcia S. Am J Cardiol 2008;102:809-13

18. Decrease-v trial • CARP showed that prophylactic coronary revascularization does not improve postoperative outcome • Verify whether at least those patients with severe CAD benefit from this strategy • Patients with ≥3 risk factors underwent stress imaging; those with extensive stress-induced ischemia (≥5 segments or ≥3 walls) were randomized • All received beta-blockers, and antiplatelet therapy was continued during surgery Poldermans D. JACC 2007;49:1763–9

19. Decrease-v: flowchart

20. Decrease-v: results All-Cause Death or Myocardial Infarction at 1 year Prophylacticrevascularization Prophylacticrevascularization P>0.2 P>0.2 Best medicaltherapy Best medicaltherapy Poldermans D. JACC 2007;49:1763–9

21. Decrease-v: limitations Poldermans D. JACC 2007;49:1763–9

22. Systematic vs. selective coronary angiography • CARP and DECREASE-V showed that prophylactic coronary revascularization does not improve postoperative outcome, but have many limitations • 30-day cardiovascular complication rates of vascular surgery remain as high as 15-20% (mortality 3-5%) • Patients with Revised Cardiac Risk Index ≥2 were randomized to “systematic” or “selective” (after stress imaging) coronary angiography and consequent revascularization • All received beta-blockers, and aspirin therapy was continued during surgery Monaco M. JACC 2009;54:989–96

23. Systematic vs. selective coronary angiography Monaco M. JACC 2009;54:989–96

24. Systematic vs. selective coronary angiography Systematicangiography Selectiveangiography Systematic Selective Monaco M. JACC 2009;54:989–96

25. Registry of 624 consecutive vascular surgery patients Landesberg G. Eur Heart J 2007;28:533-9

26. Revascularization vs medical therapy for stable cad Hachamovitch R. Circulation 2003; 107:2900-6

27. benefit of revascularizationfor stable cad 20% Hachamovitch R. Circulation 2003; 107:2900-6

28. courage: PCI VS MEDICAL THERAPY FOR STABLE CAD Boden WE et al. NEJM 2007;356:1503-16

29. COURAGE Trial The Revenge of the Clinical Cardiologist Interventionalists Vs. ClinicalCardiologists

30. Courage trial • Population: 2287 pts with objective evidence of myocardial ischemia and significant CAD • Primary end point: death and non-fatal MI • Results: • PCI showed no benefit in the primary end point vs. medical therapy (19% vs. 18.5%, p=0.62) • PCI showed a significant benefit in angina relief at 1 and 3 years, that was not sustained at 5 years Boden WE et al. NEJM 2007;356:1503-16

31. limitations: Enrollment • 32,468 (91.4%) patientswereexcluded! • -8,677 didnotmeetinclusioncriteria • 5,155 hadundocumented ischemia • 3,961 due to vessel anatomy • -6,554 wereexcludedforlogistic • reasons • -18,360 hadone or more exclusions • 4,513 hadundergonerecent (<6 mo) revascularization • 4,939 hadinadequate EF • 2,987 hadcontraindicationto PCI • 2,542 had a seriouscoexistingillness • 1,285 hadconcomitantvalvulardisease • 1,203 hadclass IV angina • 1,071 had a failureofmedicaltherapy • 947 had LM stenosis >50% • 722 hadonly PCI restenosis (no newlesion) • 528 hadcomplicationsafterMI Highly selected study population ! Boden WE et al. NEJM 2007;356:1503-16

32. Limitations: end point choice All cause deathwas a wrong endpoint (itshouldhavebeencardiacdeath!) Boden WE et al. NEJM 2007;356:1503-16

33. Critical point: crossover to PCI • 15.7%of patients randomized to PCI were not treated or did not complete follow-up vs. 8.5% of the patients assigned to OMT who were lost to follow-up. • Trial design projection:no more than 10% of OMT patients would cross over to PCI. • Reality:25.5%of OMTcrossed overto PCI but their outcome was evaluated as they were on drug therapyonly(intention-to-treat principle). • For various reasons,4%of the PCI patients were not treated with an intervention but their outcome was evaluated as they were (intention-to-treat principle)

34. Limitations: incomplete revasc 1149 patients total 46 (4%) procedure not attempted 27 (2%) no lesions crossed 1077 patients (94%) had PCI attempted 1577/1688 lesions had PCI success (93%) 787 patients (69%) had 2 or 3 vessel ds. 590 pts (59%) received 1 stent 416 pts (41%) received ≥2 stents At least 371 of 787 pts (47%) with multivessel disease had incomplete revascularization 97% BMS 3% DES Boden WE et al. NEJM 2007;356:1503-16

35. Limitations: MI definition Anycardiacbiomarkerelevation Spontaneous MI PCI+OMT=108 OMT=119 Periprocedural MI PCI+OMT=35 OMT=9 GP IIb/IIIa inhib. and clopidogrel, which minimize periprocedural MIs, were rarely used A 2.8% MI rate seems high for patients with stable angina Boden WE et al. NEJM 2007;356:1503-16

36. Clinical relevance of postprocedural MI ICTUS trial: periproceduralMI, definedas CK-MB>ULN, is mostly inconsequential. Only large MIs should be included in a meaningful clinical end point 7.9% 6.6% 4-Year Mortality (%) HR 0.88 (0.41-1.92) p=0.75 Yes No In-hospital MI Hirsh A et al. Lancet 2007;369:827-35

37. limitations: compliance to medical Tx • LDL <85 mg/dl in ~ 70% of pts • SBP <130 mmHg in~ 65% of pts • DPB <85 mmHg in ~ 94% of pts • HgBA1C <7.0% in ~ 45% of pts

38. Limitations: compliance to medical therapy CRUSADE registry (1995-2002) Duke Clinical Research Institute, AHA 2005.

39. PCI in Chronic Stable Coronary Syndromes… • Improves symptoms from coronary lesions • usually better than drugs • similar to bypass surgery (in most patients) • May reduce death and MIs in some patients

40. ESC guidelinesforpci (2005): stable cad Silber S. Eur Heart 2005;26:804–847

41. ESC guidelines non-cardiac surg.:Stress testing Poldermans D. Eur Heart J 2009 Aug 27 [Epub] 

42. ESC guidelines non-cardiac surg.:prophylactic revascularization Poldermans D. Eur Heart J 2009 Aug 27 [Epub] 

43. conclusions • Patientswith PAD have a 4- to 10-fold increase in cardiacdeath and MI • Patientsundergoingvascularsurgerystillhave a high perioperativecardiacmortality and morbidity • CARP and DECREASE-V failedto prove a clinical benefit fromprophylacticcoronaryrevascularizationbeforevascularsurgery, even in patientswithlargemyocardial ischemia • … so why screening for CAD in PAD patients?

44. conclusions • Even in patientswith severe PAD, requiringvascularsurgery, systematic screening isprobablyunnecessary, considering the lackof benefit ofprophylacticcoronaryrevascularization • Patientswith multiple clinicalriskfactorsforincreasedcardiacriskprobablydeservecoronaryangiography, particularlypatientswith CHF and insulin-dependentdiabetes

45. conclusions • Neither the presenceoflargemyocardial ischemia at stress imagingnor the angiographicseverityofcoronarystenoses are efficientmeanstoidentifythosepatientswith PAD who are at highestriskof acute coronaryevents • Thereisstillroomforinvestigation!

48. AIM of TRIAL To determine the impact of a strategy of systematic coronary angiography on immediate- and long-term outcome of patients at medium-high risk who were undergoing surgical treatment of peripheral arterial disease.

49. 208 PATIENTS werefoundtohave a RevisedCardiacRiskIndex (RCRI) ≥ 2 and wererandomizatedinto 2 groups: • The “selectivestrategy” group A consistedof 103 patientswhoeventuallyunderwentcoronaryangiography at the timeofperipheralangiographyas a resultof a positive stress test • The “systematicstrategy” group B consistedof 105 patientswhounderwentoutrightcoronaryangiography at the timeofperipheralangiography, without a noninvasive test beingperformed.