Revascularization Strategies (SYNTAX, BARI 2D, and STICH) Angioplasty Summit 2010 Seoul, Korea. David R. Holmes, MD Mayo Clinic Rochester, MN

Transcription

1 Revascularization Strategies (SYNTAX, BARI 2D, and STICH) Angioplasty Summit 2010 Seoul, Korea David R. Holmes, MD Mayo Clinic Rochester, MN

2 Presenter Disclosure Information David R. Holmes, Jr., M.D. Revascularization Strategies (SYNTAX, BARI 2D, and STICH) The following relationships exist related to this presentation: No relationships to disclose

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4 STICH Trial Background Surgical ventricular reconstruction has been developed for management of heart failure related to ventricular remodeling caused by coronary artery disease. It has been suggested that surgical ventricular reconstruction may reduce rate of hospitalization and improve ventricular function better than CABG alone. Jones RH et al: N Engl J Med 360:1705, 2009

5 STICH Trial 1000 patients with EF 35%, amenable to CABG randomly assigned to either CABG plus surgical ventricular reconstruction vs CABG alone Primary end point: Composite of death from any cause and hospitalization for cardiac causes Jones RH et al: N Engl J Med 360:1705, 2009

6 Probability Death from Any Cause or Hospitalization for Cardiac Causes P=0.90 CABG STICH Trial CABG + SVR Death from Any Cause P=0.98 CABG + SVR CABG No. at risk Years since randomization CABG CABG SVR Jones RH et al: N Engl J Med 360:1705, Years since randomization

7 STICH Trial Primary Outcome HR for P for Subgroup Pt (no.) event (95% CI) interaction Age 0.48 ³65 yr ( ) <65 yr ( ) NYHA heart failure class 0.97 I or II ( ) III or IV ( ) CCS angina class 0.39 No angina or ( ) or class II Class III or IV ( ) LVEF % ( ) >28% ( ) Jones RH et al: N Engl J Med 360:1705, CABG + SVR CABG better better

8 Conclusions: Adding surgical ventricular reconstruction to CABG reduced the left ventricular volume, as compared with CABG alone. However, this anatomical change was not associated with a greater improvement in symptoms or exercise tolerance or with a reduction in the rate of death or hospitalization for cardiac causes. (ClinicalTrials.gov number, NCT )

9 119 articles referenced by PubMed related To the COURAGE Trial

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12 True, True and Unrelated: The results of Hypothesis II of the STICH Trial will remain true, true and unrelated and will go down as an expensive but clinically meaningless exercise in surgical research. Conte J, Johns Hopkins University J Heart Lung Transplant, 29: , 495, 2010

13 The STICH Trial: Misguided Conclusions The STICH Trial conclusions show that statisticians can defy nature from a flawed database. Buckberg GD, UCLA, J Thorac Cardiovasc Surg, 138: , 65, 2009

14 To Reconstruct or Not The real message of the STICH Trial is this: if one is pondering treatment of patients with poor ventricular function and mild aneurysmal dilatation, do NOT perform SVR surgery because if you do not send the patient to heaven (i.e. kill them) you will only prolong his or her and your own suffering with no clinical benefit. Kieser TM, Univ. of Calgary, J Thorac Cardiovasc Surg,, 138: , 65, 2009

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16 BARI 2D Clinical Trial Compare treatment strategies for patients with Type 2 diabetes mellitus Documented CAD suitable for elective revascularization (1 or more significant lesions) Documented ischemia No prior CABG or PCI within the last 12 months

17 Revascularization Decision BARI 2D Cardiologist a priori selected revascularization method based on clinical and angiographic factors Percutaneous coronary intervention or Coronary artery bypass graft surgery

18 BARI 2D Trial: Study Design 2368 patients with mild to moderate CAD and Type 2 diabetes prior r to randomization. Prospective. Randomized. Mean follow-up 5.3 years CABG Stratum (N= 763) R PCI Stratum (N= 1605) R OMT alone (N= 385) CABG +OMT (N= 378) OMT alone (N= 807) PCI +OMT (N= 798) R R R R Provision (N= 194) Sensitization (N= 191) Provision (N= 190) Sensitization (N= 188) Provision (N= 399) Sensitization (N= 408) Provision (N= 402) Sensitization (N= 396) g g Primary Endpoint: Death (from any cause) Secondary Endpoint: Composite of Death, MI, or Stroke BARI 2D Study Group, NEJM 2009

19 BARI 2D 1593 patients with MVD CABG: 11% suitable for PCI 44% 56% PCI: 49% suitable for CABG Kim LJ et al, JACC Intv 2:384-92, 2009

20 BARI 2D Selection of CABG rather than PCI Based largely on greater extent, severity and complexity of CAD More likely in patients >65 years Less likely in patients with prior PCI More likely in non U.S. centers Less likely after introduction of DES Kim LJ et al, JACC Intv 2:384-92, 2009

21 Conclusions: The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT )

22 BARI 2D Trial: Primary Endpoint Death (%) 20% 15% 10% 5% 0% 13.2% 13.5% Revasc. p = 0.97 n =155 n =161 OMT The 5-year 5 death rate for the group receiving revascularization plus optimal medical therapy was 13.2% vs. 13.5% in the group receiving optimal medical therapy alone The difference between the two treatment groups did not reach statistical significance BARI 2D Study Group, NEJM 2009

23 Prompt Revascularization vs Medical Therapy All-Cause Mortality Death/MI/Stroke Survival (%) Prompt revascularization Intensive medical 88.3% rev 87.8% med Event free (%) 77.2% rev 75.9% med 20 P=0.97 P= Years since randomization Years since randomization

24 BARI 2D Trial: Secondary Endpoint Cardiovascular Event (%) 25% 20% 15% 10% 5% 0% 11.6% 10.0% n=118 n= % 2.8% n=30 n=33 n= % 22.6% n=283 MI Stroke Death/MI/Stroke Revasc. OMT The rates of MI, stroke and the combined secondary endpoint of death, MI, and stroke were similar between the group receiving revascularization plus optimal medical therapy vs. the group receiving optimal medical therapy alone. The difference between the two treatment groups for the combined secondary endpoint of death, MI, and stroke did not reach statistical significance (p=0.70) BARI 2D Study Group, NEJM 2009

25 BARI 2D Trial: Primary Endpoint Death (%) 20% 15% 10% p = % 13.5% The 5-year 5 death rate for the group receiving insulin sensitization therapy was 13.2% vs. 13.5% in the group receiving insulin provision therapy. 5% 0% n =156 n =160 Sens. Prov. The difference between the two treatment groups did not reach statistical significance. BARI 2D Study Group, NEJM 2009

26 Insulin Sensitization vs Insulin Provision All-Cause Mortality Death/MI/Stroke % IS 77.7% IS Survival (%) Insulin sensitization Insulin provision 87.9% IP Event free (%) 75.4% IP 20 P=0.89 P= Years since randomization Years since randomization

27 BARI 2D Primary Conclusion Overall similar mortality and CV events Prompt revascularization vs delayed or no revascularization Insulin sensitization vs insulin provision Among high-risk patients selected for CABG Prompt revascularization reduces major CV events compared with delayed or no revascularization (P=0.01) Among lower-risk risk patients selected for PCI Prompt revascularization and delayed or no revascularization had similar rates for major CV events

28 Cumulative Rate of First Revascularization % 96% 97% 97% 97% 97% 80 79% Prompt revascularization Event rate (%) % 19% 28% 33% 38% Intensive medical 42% 0 3% 0 6 mo Years since randomization

29 Conclusions Optimal medical therapy is required for diabetic patients with CAD Despite optimal medical therapy, 42% of diabetic patients will still undergo revascularization during 5 years FU Revascularization strategies chosen depend in large part on severity and extent of disease Clinical decision making still works

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31 SYNTAX Left Main Trial Patient Disposition All randomized patients (n=1,800) Patients with 3-vessel 3 disease (n=1,095) Patients with left main disease (n=705) CABG (n=348) TAXUS (n=357) Withdrew consent (n=12) Lost to follow-up (n=1) Discontinued treatment (n=1) 12-month clinical follow-up CABG (n=336, 96.6%) Morice MC et al: Circ, 2010 (in press) 12-month clinical follow-up TAXUS (n=355, 99.4%)

32 SYNTAX Left Main Trial Cumulative event rate (%) All-Cause Death P= % 4.2% CABG (n=348) PCI (n=357) Months since allocation Morice MC et al: Circ, 2010 (in press)

33 Cumulative event rate (%) SYNTAX Left Main Trial CABG (n=348) Myocardial Infarction P= % Months since allocation Morice MC et al: Circ, 2010 (in press) PCI (n=357) CVA P= % 2.7% Months since allocation 0.3%

34 SYNTAX Left Main Trial Cumulative event rate (%) CABG (n=348) Repeat Revascularization P= % 6.7% Months since allocation Morice MC et al: Circ, 2010 (in press) PCI (n=357) Death/ CVA/MI P= Months since allocation 9.1% 7.0%

35 SYNTAX Left Main Trial 1-Year MACCE Cumulative event rate (%) Mean baseline SYNTAX score CABG 15.5±4.3 TAXUS 15.7±4.4 D-5.3 (-13.6,( 3.0) P=0.19 CABG (n=103) TAXUS (n=118) 13.0% 7.7% Months since allocation Morice MC et al: Circ, 2010 (in press) Mean baseline SYNTAX score CABG 27.2±3.0 TAXUS 27.0± D-2.9 (-12.8,( 7.0) P=0.53 CABG (n=92) TAXUS (n=103) 15.5% 12.6% Months since allocation Mean baseline SYNTAX score CABG 42.1±7.6 TAXUS 43.8±9.1 D12.4 (3.1, 21.7) P=0.008 CABG (n=150) TAXUS (n=135) 25.3% 12.9% Months since allocation

36 SYNTAX Trial Conclusions Patients with LM disease who had revascularization with PCI had comparable safety and efficacy outcomes to CABG at 1 year. Morice MC et al: Circ, 2010 (in press)

37 MACCE to 2 Years Left Main Population Patients, % CABG (n=348) Death/CVA/MI Revasc TAXUS (n=357) P=0.48 P=0.01 P= MACCE Similar LM MACCE rates through 2 years between PCI and CABG PCI of LM is safe and feasible Cumulative MACCE (%) Cumulative MACCE (%) Cumulative MACCE (%) SYNTAX Score 33 P= % 17.8% Months Since Allocation SYNTAX P=0.91 Score % 22.4% SYNTAX Score 22 Months Since Allocation P= % 15.5% Months Since Allocation

38 EuroSCORE and SYNTAX Trial Background Whether SYNTAX score should be used as a stand-alone alone tool or whether its performance may be improved by the parallel use of clinical scores focusing on co-morbidities, such as EuroSCORE, is a matter of debate. Capodanno D et al: Am Heart J 159:103, 2010

39 The Global Risk Score EuroScore and SYNTAX Score 255 Patients with LMCA PCI SYNTAX score < >27 EuroSCORE >6 L L I L L I I I H Capodanno D et al: Am Heart J 159:103,

40 2-Year Survival Cardiac death-free survival (%) SYNTAX Score SYNTAX score <19 SYNTAX score SYNTAX score >27 P= Days 96.1% 94.6% 78.1% Capodanno D et al: Am Heart J 159:103, 2010 Global Risk Score Low GRC Intermediate GRC High GRC P< Days 98.4% 84.0% 68.6%

41 Conclusions: We found a significant improvement in the prediction of cardiac mortality with the inclusion of EuroSCORE in a SYNTAX score-based model. The degree of reclassification between treatment threshold categories indicates that clinical and angiographic information are both important for assessing individual risk of patients undergoing left main PCI

42 All-Cause Death to 2 Years Cumulative event rate (%) CABG (n=897) Before 1 year 3.5% vs 4.4% P=0.37 P=0.24 Months since allocation TAXUS (n=903) After 1 year 1.5% vs 1.9% P= % 4.9%

43 Repeat Revascularization to 2 Years Cumulative event rate (%) CABG (n=897) Before 1 year 5.9% vs 13.5% P<0.001 P<0.001 Months since allocation TAXUS (n=903) After 1 year 3.7% vs 5.6% P= % 8.6%

44 MACCE to 2 Years by SYNTAX Score Tercile Low Scores (0-22) Cumulative event rate (%) CABG (n=275) Mean baseline SYNTAX score CABG 16.6±4.0 TAXUS 16.7±4.1 P=0.63 Months since allocation TAXUS (n=299) % 17.4%

45 MACCE to 2 Years by SYNTAX Score Tercile Intermediate Scores (23-32) 32) Cumulative event rate (%) CABG (n=300) Mean baseline SYNTAX score CABG 27.4±2.8 TAXUS 27.3±2.8 P=0.06 Months since allocation TAXUS (n=310) % 16.4%

46 MACCE to 2 Years by SYNTAX Score Tercile High Scores ( 33)( Cumulative event rate (%) CABG (n=315) Mean baseline SYNTAX score CABG 41.5±7.1 TAXUS 41.7±7.8 P<0.001 Months since allocation TAXUS (n=290) % 15.4%

47 2-Year Outcomes in 3VD and LM Subgroups CABG TAXUS 40 P=0.11 P<0.001 P< P=0.48 P=0.01 P=0.27 Patients (%) Death/CVA/MI Revasc MACCE 0 Death/CVA/MI Revasc MACCE 3 vessel disease n=1095 Left main disease n=

48 Summary I In the SYNTAX randomized patients, 2-year 2 MACCE rates were significantly higher for PCI than CABG, mainly driven by higher repeat revascularization in the PCI arm Significant increase of MI compared to CABG at 2 years driven by higher PCI MI rate between years 1 and 2 Significantly higher CVA rate in CABG compared to PCI with the majority of CVAs occurring in the first year Composite safety (death/cva/mi) remains similar between arms at 2 years MACCE rates at 2 years not significantly different for patients with a low (0-22) or intermediate (23-32) 32) baseline SYNTAX score; for patients with high SYNTAX scores (³33), MACCE continued to be increased at 2 years in patients treated with PCI

49 Summary II In the predefined subgroups of patients with either 3VD or LM disease Safety outcomes (death/cva/mi) in the 3VD group were similar for PCI and CABG, but the 2-year 2 revascularization and MACCE rates favored CABG In the LM group, safety outcomes and MACCE rates were similar for PCI and CABG, but the 2-year 2 revascularization rate was lower in the CABG group The 2-year 2 SYNTAX results suggest that CABG remains the standard of care for patients with complex disease (high SYNTAX scores); however, PCI may be an acceptable alternative revascularization method to CABG when treating patients with less complex (low or intermediate SYNTAX score) disease

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51 Improve Survival Improve Symptoms Angina CHF Decrease infarction Improve rhythm control Decreasing need for optimal medical therapy Salvage myocardium

52 In your case, Dave, there s a choice¾elective surgery, outpatient medical therapy, or whatever s in the box that our lovely Carol is holding.

53 Blood is better than drugs for ischemic myocardium Rahimtoola The more disease present, the more blood helps Surgeons can be vicious Modified

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55 Revascularization Strategies Issues Patient demographics Lesion specifics Specific revascularization Timing of the specific revascularization What are the metrics for comparing these issues? At what time do we compare the metrics?

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57 SCENARIOS 50-year year-old Mild, stable angina Proximal RCA stenosis Normal LV function 50-year year-old Unstable angina EF 42% Severe complex 3VD 50-year year-old CHF EF 23% LAD 30% Prox RCA 50% Circ 60%

58 Revascularization Goals Prolong survival Reduce infarction Reduce CHF Alleviate symptoms Reduce ischemia Reduce repeat hospitalization Reduce medical costs

59 Revascularization Goals What is the comparator? How long do we compare against what we are comparing with?

60 Adjunctive therapy Specific anatomic subset Specific revascularization strategy and performance Specific patient demographics

61 Murder Parking Ticket

62 Murder Parking Ticket

63 SYNTAX STICH BARI 2D

64 Days Weeks Months 1 yr 2 yrs >2 yrs

65 Conclusions: The SXscore is a useful tool to predict cardiac mortality and MACE in patients undergoing percutaneous revascularization of the left main coronary artery

66 SYNTAX and Unprotected LMCA Cardiac mortality (%) SXscore 18 SXscore >18-27 SXscore >27 MACE (%) Days No. at risk I tertile II tertile III tertile Days No. at risk I tertile II tertile III tertile Capodanno D et al: Cardiovasc Intervent 2:302,

67 50 SYNTAX and Unprotected LMCA Cardiac Death Node 1 (n=255) SYNTAX score P< >34 Node 2 (n=195) Node 3 (n=60) Days Capodanno D et al: Cardiovasc Intervent 2:302, Days

68 50 SYNTAX and Unprotected LMCA MACE Node 1 (n=255) SYNTAX score P< >37 Node 2 (n=218) Node 3 (n=42) Days Capodanno D et al: Cardiovasc Intervent 2:302, Days

69 Title/drp author: WT/BK Holmes, David Sub/drp Job#: YW105/BK Subject: SYNTAX & Upprot. LMCA, Capodanno Background: BU3 Plot/brdr: open/bu41 Banner/brdr: /BU41 x, y only Side title: YW105 /colhdgs: YW105 Text: WT/BK Highlight: YO114 Subdue: BU31 Footnotes: BU41 COLOR REFERENCE ONLY PPT shooting instructions PPT File to Server (4 images) Artist: mls Start Date: Match: Mayo2bu (CP )

70 Cumulative incidence (%) P=0.461 SYNTAX Score and UPLMCA Unadjusted 2-Year 2 Mortality SYNTAX Score % 4.5% 6.2% Months PCI CABG 8.1% SYNTAX Score >34 P< % 6.8% 8.5% Months PCI CABG 32.7% Number at risk PCI CABG Capodanno D et al: J Am Coll Cardiol Intv 2:731,

71 SYNTAX Score and UPLMCA Unadjusted and Adjusted 2-Year 2 RR of Death with PCI or CABG SYNTAX score 34 Favors PCI Favors CABG Log (hazard ratio) HR (95% CI) P Unadjusted 1.30 ( ) 0.46 Adjusted 0.81 ( ) 0.64 SYNTAX score >34 Unadjusted 4.24 ( ) <0.001 Adjusted 2.54 ( ) Capodanno D et al: J Am Coll Cardiol Intv 2:731,

72 SYNTAX Score and UPLMCA Complete revascularization (%) SYNTAX score 34 SYNTAX score >34 D=40.6% PCI D=12.5% CABG Capodanno D et al: J Am Coll Cardiol Intv 2:731,

73 Title/drp author: WT/BK Holmes, David Sub/drp Job#: YW105/BK Subject: SYNTAX Score and UPLMCA, Capodanno Background: BU3 Plot/brdr: open/bu41 Banner/brdr: /BU41 x, y only Side title: YW105 /colhdgs: YW105 Text: WT/BK Highlight: YO114 Subdue: BU31 Footnotes: BU41 COLOR REFERENCE ONLY PPT shooting instructions PPT File to Server (3 images) Artist: ma Start Date: Match: Mayo2bu (CP )

74 Conclusions: We found a significant improvement in the prediction of cardiac mortality with the inclusion of EuroSCORE in a SYNTAX score-based model. The degree of reclassification between treatment threshold categories indicates that clinical and angiographic information are both important for assessing individual risk of patients undergoing left main PCI

75 The Global Risk Score SYNTAX score < >27 EuroSCORE >6 L L I L L I I I H Capodanno D et al: Am Heart J 159:103,

76 2-Year Survival Cardiac death-free survival (%) SYNTAX Score SYNTAX score <19 SYNTAX score SYNTAX score >27 P= Days 96.1% 94.6% 78.1% Capodanno D et al: Am Heart J 159:103, 2010 Global Risk Score Low GRC Intermediate GRC High GRC P< Days 98.4% 84.0% 68.6%

77 Title/drp author: WT/BK Holmes, David Sub/drp Job#: YW105/BK Subject: Euro Score & SYNTAX, Capodanno Background: BU3 Plot/brdr: open/bu41 Banner/brdr: /BU41 x, y only Side title: YW105 /colhdgs: YW105 Text: WT/BK Highlight: YO114 Subdue: BU31 Footnotes: BU41 COLOR REFERENCE ONLY PPT shooting instructions PPT File to Server (3 images) Artist: mls Start Date: Match: Mayo2bu (CP )

78 STICH Trial Baseline Characteristics CABG with surgical CABG alone ventricular reconstruction Variable (n=499) (n=501) Demographic characteristics Age (yr) Median Interquartile range Female sex, no. (%) 78 (16) 69 (14) Medical history MI, no. (%) 435 (87) 437 (87) Diabetes, no. (%) 173 (35) 171 (34) Chronic renal insufficiency 42 (8) 43 (9) Stroke, no. (%) 28 (6) 28 (6) Angina class III 203 (41) 205 (41) IV 45 (9) 39 (8) NY Heart Assoc HF class III 210 (42) 218 (44) IV 31 (6) 26 (5) Jones RH et al: N Engl J Med 360:1705,

79 Variable Coronary anatomy No. of vessels with stenosis of ³50%, no. (%) STICH Trial Baseline Characteristics CABG alone (n=499) Jones RH et al: N Engl J Med 360:1705, 2009 CABG with surgical ventricular reconstruction (n=501) 1 36 (7) 51 (10) (29) 131 (26) (64) 319 (64) Stenosis of left main coronary artery, no. (%) 50-74% 72 (14) 61 (12) ³75% 31 (6) 33 (7) ³75% stenosis of proximal 388 (78) 369 (74) LAD coronary artery, no. (%)

80 STICH Trial CCS Angina Class No angina Class I-III II Class III-IV IV CABG CABG + SVR Pt (no.) Baseline (n=499) 8 88 Latest follow-up (n=435) Baseline (n=501) 6 83 Latest follow-up (n=428) Jones RH et al: N Engl J Med 360:1705,

81 STICH Trial NYHA Heart Failure Class Class I Class II Class III-IV IV CABG CABG + SVR Pt (no.) Baseline (n=499) Latest follow-up (n=435) Baseline (n=501) Latest follow-up (n=429) Jones RH et al: N Engl J Med 360:1705,

82 Title/drp author: WT/BK Holmes, David Sub/drp Job#: YW105/BK Subject: STICH Trial Background: BU3 Plot/brdr: open/bu41 Banner/brdr: /BU41 x, y only Side title: YW105 /colhdgs: YW105 Text: WT/BK Highlight: YO114 Subdue: BU31 Footnotes: BU41 COLOR REFERENCE ONLY PPT shooting instructions PPT File to Server (7 images) Artist: mls Start Date: Match: Mayo2bu (CP )

83 Conclusions: The majority of diabetic patients with multivessel disease were selected for PCI rather than CABG. Preference for CABG over PCI was largely based on angiographic features related to the extent, location, and nature of CAD, as well as geographic, demographic, and clinical factors. (Bypass Angioplasty Revascularization Investigation in Type 2 Diabetes [BARI 2D]; NCT )

84 BARI 2D 100 US (n=714) CABG-intended patients (%) Non-US (n=594) n=224 n=105 n=180 n=151 n=164 n=166 n=146 n= Jeopardized myocardium (in quartiles) (%) Kim LJ et al: J Am Coll Cardiol Intv 2:384,

85 Selection of CABG Rather than PCI Non-US vs US Rand after DES available Male sex Age ³65 years Prior PCI Triple vessel disease LAD ³70% stenosis Prox LAD ³50% stenosis Total occlusion Class C lesions ³ Kim LJ et al: J Am Coll Cardiol Intv 2:384, Log scale

86 Title/drp author: WT/BK Holmes, David Sub/drp Job#: YW105/BK Subject: BARI 2D Kim Background: BU3 Plot/brdr: open/bu41 Banner/brdr: /BU41 x, y only Side title: YW105 /colhdgs: YW105 Text: WT/BK Highlight: YO114 Subdue: BU31 Footnotes: BU41 COLOR REFERENCE ONLY PPT shooting instructions PPT File to Server (3 images) Artist: mls Start Date: Match: Mayo2bu (CP )

87 Stable Angina Should be Approached with PCI 14 th Annual 2009 Cardiology at Cancun February 2009 David R. Holmes, MD Mayo Clinic Rochester, MN

88 Presenter Disclosure Information David R. Holmes, Jr., M.D. Stable Angina Should be Approached with PCI The following relationships exist related to this presentation: No relationships to disclose

89 How Do We Choose Issues Physician Patient, Family Societal, Health Plan

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91 Expectations Economic stimulus package will work The bathing suit will cover as well as it used to The sun will shine in Cancun while we are there I will not get a headache from the Tequila

92 Mr. or Mrs. Mainstreet Want to live forever Want good health and thinness without sweat or carrot sticks Want to avoid a heart attack or death Most of all, want to avoid a stroke Want to go to heaven Certainly want to avoid surgery Would be nice if it improved their skills at shopping, bargain hunting, golf or fishing

93 Willpower lasts about 30 days and is soluble in alcohol

94 Which Would You Rather Have? Option A Option B LAD 70 0 RCA Circ Coated Stent High dose statin

95 Increasingly Common

96 Psychologic Distress and CAD 381 patients (311 men, 70 women) referred for cardiac rehabilitation Assessment of psychologic distress using self report inventory (SCL 90 R) Distressed defined as SCL 90 R scores >90% for outpatient adults Gau GT et al: Mayo Clin Proc 70:734-42, 2007

97 Cumulative Risk of Early Cardiovascular Rehospitalization % Distressed Non-distressed Gau GT et al: Mayo Clin Proc 70:734, 2007 Days post-discharge from index event CP

98 Psychologic Distress and CAD Psychologic distress adversely affects the prognosis of CAD patients Gau GT et al: Mayo Clin Proc 70:734-42, 2007

99 CP

100 The key to surviving a heart attack is promptly recognizing the warning signals and getting immediate medical attention. Patient Expectations Montana Heart Center Do Not Delay Seeking Treatment. It Could Save Your Life. The Quicker You Seek Treatment Following Symptoms, The Better The Outcome! Treating A Heart Attack - Dealing With A Heart Attack: Heart Disease If you have a heart attack and reach the hospital in time, chances are very good that you will walk out of the hospital within a week or even sooner. (provided by the Faculty of the Harvard Medical School) Fast Action Saves Lives Calling is the fastest way to get lifesaving treatment. If you or someone you are with has any symptoms of a heart attack, call immediately

101 Patient Expectations If I or my spouse recognizes heart symptoms on time and gets me to the cardiologist and the cardiologist says it is my heart and that he/she can treat it, then that treatment will save my life.

102 PCI What do we know? Treatment of choice for acute STEMI; documented to decrease death and recurrent MI Improves outcome in selected patients with ACS Reduces ischemia and symptoms in selected patient subsets

103 PCI What do we know? It is not perfect It treats only the treated area It has the potential for ST or restenosis which while uncommon still occurs It does not do much to reduce weight, stop smoking, exercise, control BP, decrease BS or improve lipids

104 Aphorism Blood is better than drugs for the ischemic myocardium

105 A burglar broke into a house one night. He shined his flashlight around, looking for valuables; and when he picked up a CD player to place in his sack, a strange, disembodied voice echoed from the dark saying, Jesus is watching you

106 He nearly jumped out of his skin, clicked his flashlight off, and froze. When he heard nothing more after a bit, he shook his head, promised himself a vacation after the next big score, then clicked the light on and began searching for more valuables. Just as he pulled the stereo out so he could disconnect the wires, clear as a bell he heard, Jesus is watching you

107 Freaked out, he shined his light around frantically, looking for the source of the voice. Finally, in the corner of the room, his flashlight beam came to rest on a parrot. Did you say that? he hissed at the parrot. Yep,, the parrot confessed, then squawked, I m m just trying to warn you.

108 The burglar relaxed, Warn me, huh? Who in the world are you? Moses,, replied the bird. Moses? Moses? the burglar laughed. What kind of people would name a bird Moses?

109 The kind of people that would name a Rottweiler Jesus.

110 COURAGE Trial Multicenter randomized clinical trial Screened 35,539 patients 2,287 patients randomized Objective evidence of myocardial ischemia Stable angina Randomization PCI + optimal medical therapy vs Optimal medical therapy Boden WE, NEJM 2007; 356:

111 Survival Free of Death from Any Cause and MI 1.0 Medical therapy 0.9 PCI HR % CI P=0.62 NEJM 356(15):1512, Years No. at risk 1,138 1, ,149 1, CP

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113 COURAGE Trial Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. Boden WE, NEJM 2007; 356:

114 Paul Harvey The Rest of the Story No. of Events Outcome PCI Group Med-Rx Group HR (95% CI) P Revasc (PCI or CABG) ( ) 0.71) <0.001 Boden WE, NEJM 2007; 356:

115 Paul Harvey The Rest of the Story Outcomes - Details Large preponderence of procedural MIs death and spontaneous MI actually less after PCI 30 % of OMT patients crossed over because of failure of OMT alone

116 Chronic Stable Angina PCI is very effective in reducing or abolishing angina and improving functional status In patients treated medically, crossover to PCI is frequent PCI is not more effective than aggressive medical therapy in reducing MI and death in stable mildly symptomatic patients Should we really have been surprised

117 Quality of Life COURAGE Trial 2,287 patients with stable CAD to PCI + OMT or OMT alone QOL assessed using Seattle Angina Questionnaire and RAND 36 item health survey Weintraub WS et al: N Engl J Med 359:677-87, 2008

118 Quality of Life Freedom from Angina Angina free (%) PCI + OMT OMT P= P< P< P< P= P=0.010 P= BL Months Weintraub WS et al: N Engl J Med 359:677, 2008 CP

119 Quality of Life PCI + OMT OMT Mean score * * * * Months from baseline *P<0.01 Weintraub WS et al: N Engl J Med 359:677, 2008 CP

120 Angina Frequency Mean score PCI + OMT OMT * * * * * Months from baseline *P<0.01 Weintraub WS et al: N Engl J Med 359:677, 2008 CP

121 Quality of Life COURAGE Trial Improvement in angina frequency depended on severity at baseline Largest clinical improvement with PCI seen in patients with most severe angina at baseline. No improvement in patients with mildest angina. Weintraub WS et al: N Engl J Med 359:677-87, 2008

122 ASK A HEART DISEASE SPECIALIST Cardiac ischemia What is cardiac ischemia? How serious is it? From Ruth in Virginia Mayo Clinic cardiologist Martha Grogan, M.D. and colleagues answer select questions from readers Answer: Cardiac ischemia occurs when blood flow to the heart muscle (myocardium) is obstructed by a partial or complete blockage of a coronary artery. A sudden, severe blockage may lead to a heart attack (myocardial infarction). Cardiac ischemia may also cause a serious abnormal heart rhythm (arrhythmia), which can cause fainting or even sudden death. In some people, especially those with diabetes, cardiac ischemia may cause no signs or symptoms. A doctor may make a diagnosis of cardiac ischemia based on: Medical History, Physical examination, Electrocardiogram, Stress Test, X-rays X of coronary arteries (coronary angiogram) Treatment is directed at improving blood flow to the heart muscle.

123 Nuclear Substudy (n=314/2,287) Hypothesis: Reduction in Ischemia will be greater for patients randomized to PCI+OMT than for those randomized to OMT Serial Rest/Stress Myocardial Perfusion SPECT (MPS) To compare patient management strategy for ischemia reduction Pre-Rx = Off Meds 6-18m = On Meds Documented Pre-Rx Ischemia PCI+OMT (n=159) Repeat MPS* at m OMT (n=155) Repeat MPS* at m *Timing chosen to occur beyond window of in-stent restenosis & delayed to allow effects of medical Rx to be observed Shaw et al: J Nucl Cardiol 2006; 13: Mean = 374±50 days

124 Shaw LJ et al: Circ 117: 283, 2008 Inducible Ischemia PCI + Optimal Medical Therapy (n=159) 8.2% ( %) P= % with ³5% ischemia reduction (P=0.0004) Index 5.5% ( %) 6-18 months Mean = 2.7% (95% CI = -1.7% to -3.8%) Indicate ³5% reduction in myocardial ischemia Optimal Medical Therapy (n=155) 8.6% ( %) 18.9% with ³5% ischemia reduction Index 8.1% ( %) P< months Mean = 0.5% (95% CI = -1.6% to 0.6%) No significant reduction in ischemia CP

125 Residual Ischemia and Outcome Cumulative event-free survival Unadjusted P=0.001 Risk-adjusted P=0.09 0% (n=23) % (n=141) 5-9.9% (n=88) ³10% (n=62) Follow-up (years) Shaw LJ et al: Circ 117: 283, 2008 Hazard ratio (x-fold) Risk-adjusted P=0.09 Unadjusted P= % 5-9.9% ³10% Unadjusted Risk-adjusted CP

126 Rates of Death or MI by Residual Ischemia 40 P= P=0.023 % P= % (n=22) 1%-4.9% (n=160) 5%-9.9% (n=94) 10% (n=61) COURAGE Trial

127 COURAGE Nuclear Substudy Adding PCI to OMT results in greater reduction in ischemia compared with OMT alone Reduction of ischemia is associated with decreased death/mi Severity of residual ischemia is associated with outcome Shaw LJ et al: Circ 117: 283, 2008

128 Meta Analysis PCI in Stable Angina 17 randomized trials 7,513 patients with symptoms/signs of ischemia but no ACS 3,675 assigned to PCI 3,838 assigned to medical therapy Primary endpoint: all cause death Schomig A et al: J Am Coll Cardiol 52:894, 2008

129 Odds Ratios for Cardiac Death in Individual Trials Comparing the PCI-Based Strategy with Medical Treatment Strategy Year of Cardiac deaths/total Trial publication PCI Medical Sievers et al /44 1/44 Dakik et al /21 1/23 AVERT /177 1/164 MASS /72 2/72 Bech et al /90 2/91 ALKK /149 14/151 RITA /504 24/514 TIME /153 33/148 Hambrecht et al /50 0/51 INSPIRE /104 1/101 MASS II /205 25/203 SWISSI II /96 22/105 COURAGE / /1138 Overall 115/ /2805 Random effects model 0.74 (0.51 to 1.06) Fixed effects model 0.74 (0.57 to 0.96) P heterogeneity =0.161 ;I 2 =29% Schomig A et al: J Am Coll Cardiol 52:894, Odds ratio (95% CI) CP

130 Odds Ratios for Nonfatal Myocardial Infarction in Individual Trials Comparing the PCI-Based Strategy with medical Treatment Strategy Year of MI total Trial publication PCI Medical Sievers et al /44 0/44 ACME /115 8/112 ACME /51 6/50 ACIP /192 18/366 Dakik et al /21 0/23 AVERT /177 4/164 MASS /72 3/72 Bech et al /90 0/91 ALKK /149 12/151 RITA /504 23/514 TIME /153 18/148 Hambrecht et al /50 0/51 DANAMI /503 59/505 INSPIRE /104 7/101 MASS II /205 31/203 SWISSI II /96 40/105 COURAGE /1, /1,138 Overall 319/3, /3,838 Random effects model 0.90 ( ) Fixed effects model 0.91 ( ) P heterogeneity =0.263 ;I 2 =17% Schomig A et al: J Am Coll Cardiol 52:894, Odds ratio (95% CI) 10 CP

131 Odds Ratios for Mortality for PCI vs Medical Treatment Trials (no.) Recent MI (<4 weeks) Patients (no.) Yes 4 1,557 No 13 5,956 Angiography required before randomization Yes 14 5,999 No 3 1,514 CABG as a treatment option in PCI group Yes 4 2,072 No 13 5,441 Schomig A et al: J Am Coll Cardiol 52:894, Odds ratio (95% CI) CP

132 Conclusions These findings suggest that a PCI-based invasive strategy may improve long- term survival compared with a medical treatment-only strategy in patients with stable coronary artery disease. Schomig A et al: J Am Coll Cardiol 52:894, 2008

133 PCI and Medical Therapy Low Risk Coronary Artery Disease Multicenter randomized trial Stable low risk CAD: 1 or 2 vessel CAD with stable angina Randomization to initial medical therapy alone or PCI plus medical therapy Medical therapy recommended to the patient s physician Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008

134 Baseline Clinical and Angiographic Characteristics Initial MT PCI + MT only group group Characteristic n=192 n=192 P Age (yr) 64.2± ± Male, no. (%) 144 (75.4) 141 (75.0) Clinical Initial angina grade, no. (%) (12.9) 21 (11.7) 1 69 (37.1) 64 (35.8) 2 74 (39.8) 68 (38.0) 3 16 (8.6) 19 (10.6) 4 3 (1.6) 6 (3.3) 5 0 (0.0) 1 (0.6) Diabetes, no. (%) 76 (39.8) 76 (40.4) MI, no. (%) 28 (15.1) 25 (14.0) Previous PCI, no. (%) 54 (29.0) 44 (24.6) CABG, no. (%) 3 (1.6) 5 (2.8) Cerebrovasc disease, no. (%) 10 (5.4) 13 (7.3) Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008 CP

135 Baseline Clinical and Angiographic Characteristics Initial MT PCI + MT only group group Characteristic n=192 n=192 P Stress test, no. (%) Total patients 149 (80.1) 146 (81.6) Treadmill test 76 (40.9) 68 (38.0) Duration of treadmill 7.0± ± test, min, no. (%) Nuclear medicine 55 (29.6) 63 (35.2) Echocardiography 13 (7.0) 13 (7.3) Angiographic Vessels with disease, no. (%) (67.5) 127 (67.6) 2 62 (32.5) 61 (32.5) Ejection fraction 65.8± ± Cardiac index 3.1± ± Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008 CP

136 Stable Coronary Artery Disease Mortality: 271 deaths in PCI 335 with medical therapy 20% reduction (95% CI 0.64, 0.99) Non fatal infarction: 319 in PCI group 357 with medical therapy 10% reduction (95% CI 0.66, 1.33) Schomig A et al: J Am Coll Cardiol 52: , 904, 2008

137 Death PCI + medical therapy Initial medical therapy only Death HR 0.865; 95% CI P= Years Initial medical PCI + medical Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008 CP

138 Death and ACS PCI + medical therapy 0.8 Initial medical therapy only Death + ACS HR 0.474; 95% CI P= Years Initial medical PCI + medical Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008 CP

139 Death, ACS, CVA PCI + medical therapy Initial medical therapy only Death + ACS + CVA HR 0.541; 95% CI P= Years Initial medical PCI + medical Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008 CP

140 Death, ACS, CVA, Hospitalization PCI + medical therapy Death + ACS + CVA + hospitalization HR 0.664; 95% CI P= Years Initial medical PCI + medical Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008 Initial medical therapy only CP

141 PCI and Medical Therapy Conclusions In stable low risk CAD, PCI and medical therapy may improve long- term prognosis more effectively than medical therapy alone Nishigaki K et al: J Am Coll Cardiol Intv 1:469, 2008

142 The Bottom Line PCI is very good for the treatment of ischemia and for improving functional class and reducing angina In patients with significant ischemia, PCI improves the hard endpoints of cardiac death, nonfatal MI and need for symptom driven revascularization

143 It has long been recognized that the problems with alcohol relate not to the use of a bad thing but to the abuse of a good thing Abraham Lincoln 1861

144 Who to Stent Significant stenosis Significant ischemia Informed consent Amenable to PCI

145 ACC PCI Guidelines Asymptomatic Ischemia on CCS I/II AP PCI is reasonable for recurrent stenosis after PCI with large area of viable myocardium or high risk criteria on non- invasive testing (IIA, level of evidence C)

146 Who to Not Stent Patients who do not need revascularization People who do not need revascularization Lesions which cannot be treated Lesions which should not be treated Patients in whom another approach is better

147 Courage Trial Substudy PCI + OMT OMT P Moderate-severe pre treatment Ischemia Improved 78% 52%.007 Shaw, AHA 2007

148 Overall Survival Medical therapy PCI HR % CI P= Years No. at risk 1,138 1,073 1, ,149 1,094 1, NEJM 356(15):1512, 2007 CP

149 ACC PCI Guidelines Asymptomatic Ischemia on CCS I/II AP Reasonable in patients with >50% stenosis of LMCA, who are candidates for revascularization but are not eligible for CABG (IIA, level of evidence B)

150 BARI 2D Primary and Principal Secondary Endpoints All-cause mortality Major cardiovascular events Composite of death/mi/stroke Average follow-up 5.3 years

151 Revascularization Decision BARI 2D Cardiologist a priori selected revascularization method based on clinical and angiographic factors Percutaneous coronary intervention or Coronary artery bypass graft surgery

152 Survival (%) Years since randomization Years since randomization The BARI 2D Study Group Rates of Survival and Freedom from Major CV Events Survival, Revascularization vs Medical Therapy P=0.97 No. at risk 2,368 2,296 2,247 2,197 1,892 1,196 Event-free survival (%) P=0.70 No. at risk 2,368 2,094 1,984 1,807 1, NEJM 360:2503, 2009 Revasc Medical Rx Freedom from Major CV Events, Revascularization vs Medical Therapy Revasc Medical Rx Survival (%) Survival, Insulin Sensitization vs Insulin Provision P= Years since randomization No. at risk 2,368 2,296 2,247 2,197 1,892 1,196 Event-free survival (%) Freedom from Major CV Events, Insulin Sensitization vs Insulin Provision P=0.13 Insulin sensitization 88.2 Insulin provision 87.9 Insulin sensitization 77.7 Insulin provision Years since randomization No. at risk 2,368 2,094 1,984 1,807 1,

153 Years since randomization The BARI 2D Study Group Rates of Survival and Freedom from Major CV Events According to PCI and CABG Strata Survival (%) Survival in PCI Stratum P=0.48 Medical Rx Revasc No. at risk 1,605 1,562 1,529 1,505 1, Survival (%) Survival in CABG Stratum P=0.33 Revasc Medical Rx Years since randomization No. at risk Event-free survival (%) Freedom from Major CV Events in PCI Stratum P= Years since randomization No. at risk 1,605 1,426 1,350 1,239 1, NEJM 360:2503, 2009 Medical Rx Revasc Event-free survival (%) Freedom from Major CV Events in CABG Stratum P=0.01 Revasc Medical Rx Years since randomization No. at risk

154 There are no facts, only interpretations. -Friedrich Nietzsche