18 th eurochap european chapter congress of the international union of angiology xix mlavs 2009...

1818thth EUROCHAP EUROCHAPEuropean Chapter CongressEuropean Chapter Congressof the International Union of Angiologyof the International Union of Angiology

XIX MLAVS 2009XIX MLAVS 2009Annual Meeting of the Mediterranean LeagueAnnual Meeting of the Mediterranean League

of Angiology and Vascular Surgeryof Angiology and Vascular Surgery

Ness J. J Am Geriatr Soc 1999;47:1255-6

%

3649 subjects (average age, 64 yrs) followed-up for 7.2 years

Hooi JD. J Clin Epid 2004;57:294–300

Poldermans D. Eur Heart J 2009 Aug 27 [Epub]

30-day risk of cardiac death or myocardial infarction30-day risk of cardiac death or myocardial infarction

McFalls EO. NEJM 2004;351:2795-804

To assess the benefit of To assess the benefit of prophylactic coronary prophylactic coronary artery revascularizationartery revascularization before major vascular before major vascular surgery in patients at increased risk for surgery in patients at increased risk for perioperative cardiac complications and with perioperative cardiac complications and with clinically stable, angiographically significant clinically stable, angiographically significant coronary artery diseasecoronary artery disease

McFalls EO. NEJM 2004;351:2795-804

All patients scheduled for vascular surgery All patients scheduled for vascular surgery were screenedwere screened

Patients could be enrolled if:Patients could be enrolled if:1.1. judged at high risk of cardiac complicationsjudged at high risk of cardiac complications2.2. had >70% coronary stenosis at angiographyhad >70% coronary stenosis at angiography3.3. were amenable to PCI or CABGwere amenable to PCI or CABG

McFalls EO. NEJM 2004;351:2795-804

1654

1025

626

731

633

363

21554 11 8

29510

low cardiac riskurgent vasc. surgeryprior CABG or PCIcomorbiditiesrefusal<70% coronary stenosisnot amenable to PCI or CABGleft main diseaseEF <20%aortic stenosisrefusalrandomized

Only 8.7% of 5859 screened patients were enrolled!Only 8.7% of 5859 screened patients were enrolled!Only 8.7% of 5859 screened patients were enrolled!Only 8.7% of 5859 screened patients were enrolled!

No revasc 7.0%No revasc 7.0%No revasc 7.0%No revasc 7.0% revasc 3.6%revasc 3.6%revasc 3.6%revasc 3.6%

McFalls EO. NEJM 2004;351:2795-804

VariableVariable RevascRevasc No RevascNo Revasc P ValueP Value

(N=258)(N=258) (N=252)(N=252)

Age, yr Age, yr 65.6±11.1 65.6±11.1 67.2±10.4 67.2±10.4 0.100.10

Previous MI (%) Previous MI (%) 111 (43.0) 111 (43.0) 103 (40.9) 103 (40.9) 0.620.62

Previous CHF (%) Previous CHF (%) 31 (12.0) 31 (12.0) 19 (7.5) 19 (7.5) 0.090.09

Previous CVA (%) Previous CVA (%) 54 (20.9) 54 (20.9) 47 (18.7) 47 (18.7) 0.500.50

Diabetes (%)Diabetes (%) 97(37.6) 97(37.6) 101(40.0) 101(40.0) 0.840.84

Current smoker (%) Current smoker (%) 128 (49.6) 128 (49.6) 114 (45.2) 114 (45.2) 0.410.41

Left ventricular EF % Left ventricular EF % 54±12 54±12 55±12 55±12 0.360.36

3V disease (%) 3V disease (%) 91 (35.3)91 (35.3) 79 (31.3)79 (31.3) 0.690.69

Previous CABG (%) Previous CABG (%) 38 (14.7) 38 (14.7) 39 (15.5) 39 (15.5) 0.830.83

VariableVariable RevascRevasc No RevascNo Revasc P ValueP Value

(N=258)(N=258) (N=252)(N=252)

Age, yr Age, yr 65.6±11.1 65.6±11.1 67.2±10.4 67.2±10.4 0.100.10

Previous MI (%) Previous MI (%) 111 (43.0) 111 (43.0) 103 (40.9) 103 (40.9) 0.620.62

Previous CHF (%) Previous CHF (%) 31 (12.0) 31 (12.0) 19 (7.5) 19 (7.5) 0.090.09

Previous CVA (%) Previous CVA (%) 54 (20.9) 54 (20.9) 47 (18.7) 47 (18.7) 0.500.50

Diabetes (%)Diabetes (%) 97(37.6) 97(37.6) 101(40.0) 101(40.0) 0.840.84

Current smoker (%) Current smoker (%) 128 (49.6) 128 (49.6) 114 (45.2) 114 (45.2) 0.410.41

Left ventricular EF % Left ventricular EF % 54±12 54±12 55±12 55±12 0.360.36

3V disease (%) 3V disease (%) 91 (35.3)91 (35.3) 79 (31.3)79 (31.3) 0.690.69

Previous CABG (%) Previous CABG (%) 38 (14.7) 38 (14.7) 39 (15.5) 39 (15.5) 0.830.83

McFalls EO. NEJM 2004;351:2795-804

McFalls EO. NEJM 2004;351:2795-804

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

Coronary artery revascularization before Coronary artery revascularization before elective vascular surgery does not significantly elective vascular surgery does not significantly alter the long-term outcomealter the long-term outcome

Thus, among patients with Thus, among patients with stable cardiac stable cardiac symptomssymptoms, , preventive coronary artery preventive coronary artery revascularization cannot be recommendedrevascularization cannot be recommended

Only 8.7% of screened patients were enrolledOnly 8.7% of screened patients were enrolled Cardiac risk stratification was not uniformCardiac risk stratification was not uniform Only 32% of the enrolled patients had 3-vessel diseaseOnly 32% of the enrolled patients had 3-vessel disease CHF rate was almost double in “Revasc” armCHF rate was almost double in “Revasc” arm Relevant crossover between randomization armsRelevant crossover between randomization arms Complete revasc with PCI in 61.9%; no use of DESComplete revasc with PCI in 61.9%; no use of DES Periprocedural mortality of PCI was 1.4%Periprocedural mortality of PCI was 1.4% 3.9% mortality after uncomplicated CABG or PCI 3.9% mortality after uncomplicated CABG or PCI

before vascular surgerybefore vascular surgery

Garcia S. Am J Cardiol 2008;102:809-13


Survival 2.5 years after vascular surgerySurvival 2.5 years after vascular surgery

CARP showed that prophylactic coronary CARP showed that prophylactic coronary revascularization does not improve postoperative revascularization does not improve postoperative outcomeoutcome

Verify whether at least those patients with severe Verify whether at least those patients with severe CAD benefit from this strategyCAD benefit from this strategy

Patients with Patients with ≥3 risk factors ≥3 risk factors underwent stress underwent stress imaging; those imaging; those with extensive stress-induced with extensive stress-induced ischemiaischemia (≥5 segments or ≥3 walls) were randomized (≥5 segments or ≥3 walls) were randomized

All received All received beta-blockersbeta-blockers, and , and antiplatelet therapy antiplatelet therapy was continued during surgerywas continued during surgery

Poldermans D. JACC 2007;49:1763–9


All-Cause Death or Myocardial Infarction at 1 yearAll-Cause Death or Myocardial Infarction at 1 year

Prophylactic revascularization

Best medical therapy

P>0.2

P>0.2

Prophylactic revascularization

Best medical therapy

CARP and DECREASE-V showed that prophylactic CARP and DECREASE-V showed that prophylactic coronary revascularization does not improve coronary revascularization does not improve postoperative outcome, but have many limitationspostoperative outcome, but have many limitations

30-day cardiovascular complication rates of vascular 30-day cardiovascular complication rates of vascular surgery remain as high as 15-20% (mortality 3-5%)surgery remain as high as 15-20% (mortality 3-5%)

Patients with Patients with Revised Cardiac Risk Index ≥2 Revised Cardiac Risk Index ≥2 were were randomized to randomized to “systematic” or “selective” (after stress “systematic” or “selective” (after stress imaging) coronary angiography imaging) coronary angiography and consequent and consequent revascularizationrevascularization

All received All received beta-blockersbeta-blockers, and , and aspirin therapy aspirin therapy was was continued during surgerycontinued during surgery

Monaco M. JACC 2009;54:989–96

Monaco M. JACC 2009;54:989–96

Monaco M. JACC 2009;54:989–96

Systematic angiography

Selective angiography

Systematic

Selective

Landesberg G. Eur Heart J 2007;28:533-9

Hachamovitch RHachamovitch R. . Circulation 2003; 107:2900-6Circulation 2003; 107:2900-6

20%


Boden WE et al. NEJM 2007;356:1503-16

COURAGE Trial COURAGE Trial The Revenge of the Clinical CardiologistThe Revenge of the Clinical Cardiologist

InterventionalistsVs.Clinical Cardiologists


Population: Population: 2287 pts with objective evidence of 2287 pts with objective evidence of myocardial ischemia and significant CADmyocardial ischemia and significant CAD

Primary end pointPrimary end point: death and non-fatal MI: death and non-fatal MI ResultsResults: :

PCI showed no benefit in the primary end point PCI showed no benefit in the primary end point vs. medical therapy (19% vs. 18.5%, p=0.62)vs. medical therapy (19% vs. 18.5%, p=0.62)

PCI showed a significant benefit in angina relief PCI showed a significant benefit in angina relief at 1 and 3 years, that was not sustained at 5 at 1 and 3 years, that was not sustained at 5 yearsyears

0

10000

20000

30000

40000

50000

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d

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ized

0

10000

20000

30000

40000

50000

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ized

32,468 (91.4%) patients were excluded!32,468 (91.4%) patients were excluded!-8,677 did not meet inclusion criteria-8,677 did not meet inclusion criteria

5,155 had undocumented ischemia5,155 had undocumented ischemia3,961 due to vessel anatomy3,961 due to vessel anatomy

-6,554 were excluded for logistic -6,554 were excluded for logistic reasonsreasons-18,360 had one or more exclusions-18,360 had one or more exclusions

4,513 had undergone recent (<6 mo) 4,513 had undergone recent (<6 mo) revascularizationrevascularization4,939 had inadequate EF4,939 had inadequate EF2,987 had contraindication to PCI2,987 had contraindication to PCI2,542 had a serious coexisting illness2,542 had a serious coexisting illness1,285 had concomitant valvular disease1,285 had concomitant valvular disease1,203 had class IV angina1,203 had class IV angina1,071 had a failure of medical therapy1,071 had a failure of medical therapy947 had LM stenosis >50%947 had LM stenosis >50%722 had only PCI restenosis (no new lesion)722 had only PCI restenosis (no new lesion)528 had complications after MI528 had complications after MI

32,468 (91.4%) patients were excluded!32,468 (91.4%) patients were excluded!-8,677 did not meet inclusion criteria-8,677 did not meet inclusion criteria

5,155 had undocumented ischemia5,155 had undocumented ischemia3,961 due to vessel anatomy3,961 due to vessel anatomy

-6,554 were excluded for logistic -6,554 were excluded for logistic reasonsreasons-18,360 had one or more exclusions-18,360 had one or more exclusions

4,513 had undergone recent (<6 mo) 4,513 had undergone recent (<6 mo) revascularizationrevascularization4,939 had inadequate EF4,939 had inadequate EF2,987 had contraindication to PCI2,987 had contraindication to PCI2,542 had a serious coexisting illness2,542 had a serious coexisting illness1,285 had concomitant valvular disease1,285 had concomitant valvular disease1,203 had class IV angina1,203 had class IV angina1,071 had a failure of medical therapy1,071 had a failure of medical therapy947 had LM stenosis >50%947 had LM stenosis >50%722 had only PCI restenosis (no new lesion)722 had only PCI restenosis (no new lesion)528 had complications after MI528 had complications after MI

Highly selected study population !


All cause death was a wrong endpoint (it should have been cardiac death!)All cause death was a wrong endpoint (it should have been cardiac death!)


15.7%15.7% of patients randomized to PCI were not treated or did of patients randomized to PCI were not treated or did not complete follow-up vs. not complete follow-up vs. 8.5%8.5% of the patients assigned to of the patients assigned to OMT who were lost to follow-up.OMT who were lost to follow-up.

Trial design projection:Trial design projection: no more than no more than 10%10% of OMT patients of OMT patients would cross over to PCI.would cross over to PCI.

Reality:Reality: 25.5%25.5% of OMTof OMT crossed overcrossed over to PCI but their outcome to PCI but their outcome was evaluated as they were on drug therapywas evaluated as they were on drug therapy onlyonly (intention-(intention-to-treat principle).to-treat principle).

For various reasons,For various reasons, 4%4% of the PCI patients were not treated of the PCI patients were not treated with an intervention but their outcome was evaluated as they with an intervention but their outcome was evaluated as they were (intention-to-treat principle)were (intention-to-treat principle)

Critical point: crossover to PCI

1149 patients total1149 patients total

46 (4%) procedure not attempted46 (4%) procedure not attempted27 (2%) no lesions crossed27 (2%) no lesions crossed

1077 patients (94%) had PCI attempted1077 patients (94%) had PCI attempted

1577/1688 lesions had PCI success (93%)1577/1688 lesions had PCI success (93%)

787 patients (69%) had 2 or 3 vessel ds.787 patients (69%) had 2 or 3 vessel ds.590 pts (59%) received 1 stent590 pts (59%) received 1 stent416 pts (41%) received ≥2 stents416 pts (41%) received ≥2 stentsAt least 371 of 787 pts (47%) with multivessel At least 371 of 787 pts (47%) with multivessel disease had incomplete revascularization disease had incomplete revascularization

97% BMS97% BMS3% DES3% DES


Any cardiac biomarker elevationAny cardiac biomarker elevation

A 2.8% MI rate seems high for patients with stable anginaA 2.8% MI rate seems high for patients with stable angina

Spontaneous MISpontaneous MIPCI+OMT=108PCI+OMT=108OMT=119OMT=119

Periprocedural MIPeriprocedural MIPCI+OMT=35PCI+OMT=35OMT=9OMT=9

GP IIb/IIIa inhib. and clopidogrel, which minimize GP IIb/IIIa inhib. and clopidogrel, which minimize periprocedural MIs, were rarely used periprocedural MIs, were rarely used


Hirsh A et al. Lancet 2007;369:827-35

ICTUS trial: periprocedural MI, defined as CK-MB>ULN, is mostly inconsequential. Only large MIs should be

included in a meaningful clinical end point

ICTUS trial: periprocedural MI, defined as CK-MB>ULN, is mostly inconsequential. Only large MIs should be

included in a meaningful clinical end point

4-Y

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ity

(%)

4-Y

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Mo

rtal

ity

(%)

7.9%7.9%6.6%6.6%

HR 0.88 (0.41-1.92)p=0.75

YesYes NoNo

In-hospital MIIn-hospital MIIn-hospital MIIn-hospital MI

• LDL <85 mg/dl in LDL <85 mg/dl in ~ 70% of pts~ 70% of pts• SBP <130 mmHg inSBP <130 mmHg in ~ 65% of pts~ 65% of pts• DPB <85 mmHg in ~ 94% of ptsDPB <85 mmHg in ~ 94% of pts• HgBA1C <7.0% in ~ 45% of ptsHgBA1C <7.0% in ~ 45% of pts

21

364346

71

0

20

40

60

80

100

ASA BB Lipid ASA + BB ASA+BB+Lipid

Pa

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%)

Duke Clinical Research Institute, AHA 2005.

CRUSADE registry (1995-2002)CRUSADE registry (1995-2002)

• Improves symptoms fromImproves symptoms from coronary lesions coronary lesions

usually better than drugsusually better than drugs similar to bypass surgerysimilar to bypass surgery (in most patients) (in most patients)

• May reduce death and MIs inMay reduce death and MIs in some patients some patients

• Improves symptoms fromImproves symptoms from coronary lesions coronary lesions

usually better than drugsusually better than drugs similar to bypass surgerysimilar to bypass surgery (in most patients) (in most patients)

• May reduce death and MIs inMay reduce death and MIs in some patients some patients

PCI in Chronic StablePCI in Chronic StableCoronary Syndromes…Coronary Syndromes…PCI in Chronic StablePCI in Chronic StableCoronary Syndromes…Coronary Syndromes…

ESC GUIDELINES FOR PCI (2005):ESC GUIDELINES FOR PCI (2005):STABLE CADSTABLE CAD

Silber S. Eur Heart 2005;26:804–847

Patients with PAD have a 4- to 10-fold increase in Patients with PAD have a 4- to 10-fold increase in cardiac death and MIcardiac death and MI

Patients undergoing vascular surgery still have a Patients undergoing vascular surgery still have a high perioperative cardiac mortality and morbidityhigh perioperative cardiac mortality and morbidity

CARP and DECREASE-V failed to prove a clinical CARP and DECREASE-V failed to prove a clinical benefit from prophylactic coronary benefit from prophylactic coronary revascularization before vascular surgery, even in revascularization before vascular surgery, even in patients with large myocardial ischemiapatients with large myocardial ischemia

… … so why screening for CAD in PAD patients?so why screening for CAD in PAD patients?

Even in patients with severe PAD, requiring Even in patients with severe PAD, requiring vascular surgery, vascular surgery, systematic screening is systematic screening is probably unnecessaryprobably unnecessary, considering the lack of , considering the lack of benefit of prophylactic coronary benefit of prophylactic coronary revascularizationrevascularization

Patients with multiple clinical risk factors for Patients with multiple clinical risk factors for increased cardiac risk probably deserve increased cardiac risk probably deserve coronary angiography, particularly patients coronary angiography, particularly patients with CHF and insulin-dependent diabeteswith CHF and insulin-dependent diabetes

Neither the presence of large myocardial Neither the presence of large myocardial ischemia at ischemia at stress imaging stress imaging nor the nor the angiographic severity angiographic severity of coronary stenoses are of coronary stenoses are efficient means to identify those patients with efficient means to identify those patients with PAD who are at highest risk of acute coronary PAD who are at highest risk of acute coronary events events

There is still room for investigation!There is still room for investigation!

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.

AIM of TRIAL

208 PATIENTS were found to have a Revised Cardiac Risk Index (RCRI) ≥ 2 and were randomizated into 2 groups:

The “selective strategy” group A consisted of 103 patients who eventually underwent coronary angiography at the time of peripheral angiography as a result of a positive stress test

The “systematic strategy” group B consisted of 105 patients who underwent outright coronary angiography at the time of peripheral angiography, without a noninvasive test being performed.

The primary end point was the MACE incidence at follow-up;

The secondary end point was the occurrence of a MACE between the screening and 30 days after the surgical procedure.

END POINT

A strategy of routine coronary angiography positively impacted long-term outcome of peripheral arterial disease surgical patients at medium-high risk.

This is the first such demonstration in a randomized, prospective trial.

McFalls EO. J Vasc Surg 2007;46:694-700

P<0.001 vs. other groups

McFalls EO. J Vasc Surg 2007;46:694-700

Primary end point:Primary end point: composite of all-cause death and nonfatal MI composite of all-cause death and nonfatal MI

between screening and 30-days after the between screening and 30-days after the index surgical procedureindex surgical procedure

Secondary end point:Secondary end point: composite of all-cause death and nonfatal MI composite of all-cause death and nonfatal MI

at 1 yearat 1 year


McFalls EO. EHJ 2008;29:394–401

P=0.03

McFalls EO. EHJ 2008;29:394–401

1.1. Angina pectorisAngina pectoris2.2. Prior MIPrior MI3.3. Heart failureHeart failure4.4. Stroke/TIAStroke/TIA5.5. Renal dysfunction (serum creatinine >2 mg/dL or a Renal dysfunction (serum creatinine >2 mg/dL or a

creatinine clearance of <60 mL/min)creatinine clearance of <60 mL/min)6.6. Diabetes mellitus requiring insulin therapyDiabetes mellitus requiring insulin therapy



20%20%

85%85%

60%60%

40%40%

Primary end point:Primary end point:long-term mortalitylong-term mortality

Secondary end points:Secondary end points:myocardial infarctionmyocardial infarctionstrokestrokelimb losslimb lossdialysisdialysis

McFalls EO. NEJM 2004;351:2795-804


Survival in patients with left main diseaseSurvival in patients with left main disease

18 th eurochap european chapter congress of the international union of angiology xix mlavs 2009...

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