Medical Rx vs PCI vs CABG

Transcription

1 Medical Rx vs PCI vs CABG S. Hinan Ahmed, MD Associate Professor: Cardiology and Cardiothoracic Surgery Program Director: Interventional Fellowship Program Assoc Editor: Cath and Cardiovasc Intervention UTHSC, San Antonio There are no conflicts of interest relevant to this presentation

2 Goals of Treatment Improve symptoms angina, anginal equivalents dyspnea, heart failure Reduce morbidity myocardial infarction, ischemic cardiomyopathy, dysrhythmias hospitalization, repeat revascularization procedures Reduce mortality Cost effective therapy

3 Topics 1. Overview of treatmen strategies 2. Key randomized clinical trials CABG vs. medical rx PCI vs. medical therapy: stable angina Invasive vs. conservative: ACS/NSTEMI CABG vs PCI 3. Guidelines

4 Randomized Strategy Comparisons Invasive vs Cons. (ACS) TIMI IIIB, VANQWISH FRISC II TACTICS-TIMI 18 SWISSI-II RITA-3 ICTUS PCI vs Medicine ACME ACME VA RITA-2 AVERT COURAGE 6 smaller trials CABG vs Balloon BARI CABRI EAST GABI RITA AWESOME, 4 smaller trials CABG vs Medicine CASS VA Cooperative European Cooperative STICH 4 smaller trials CABG vs Stent ARTS (ARTS II) ERACI II SoS SIMA Leipzig FREEDOM SYNTAX and growing

5 CABG vs Medical Rx

6 CABG vs. Medical Therapy Coronary Artery Bypass Surgery Trialists Collaboration Total Mortality All studies Medical rx CABG n=1325 n=1324 Trials VA European CASS Texas Oregon NZ NZ Time from randomization (years) Yusuf S et al, Lancet 1994;344:563

7 CABG vs.medical Therapy Coronary Artery Bypass Surgery Trialists Collaboration (7 randomized trials*) Disease N med mortality at 5y OR single vessel % double vessel % triple vessel % p=.001 left main % p= CABG better Med rx *VA Coop., European Coop., CASS, Texas, Oregon, NZ, NZ Yusuf S et al, Lancet 1994;344:563

8 STICH Revascularization Hypothesis 1212 Randomized MED only Randomized CABG 99 clinical sites in 22 countries Enrollment: July 2002 May 2007 Velazquez et al, NEJM 2011;364:

9 STICH: All-Cause Mortality HR 0.86 (0.72, 1.04) P = Adjusted HR 0.82 (0.68, 0.99) Adjusted P =

10 PCI vs Medical Rx

11 Stable Angina ACME ACME VA RITA-2 AVERT COURAGE 6 smaller trials

12 RITA-2: Design Second Randomized Intervention Treatment of Angina Randomized clinical trial early 1990 s PTCA (balloon) versus medical therapy 20 centers in UK & Ireland Cardiologist opinion: either medical rx or PTCA appropriate Stable angina (ACS/NSTEMI, other high risk patients excluded) 1,018 pts: 504 PTCA, 514 medical

13 RITA-2: Seven Year Outcomes Henderson RA et al., J Am Coll Cardiol 2003;42:

14 Atorvastatin Versus Revascularization Treatments (AVERT) Trial Randomized Clinical Trial mid 1990 s PTCA (with usual care) versus aggressive lipidlowering therapy Low risk patients with 1V or 2V CAD High LDL (>115 mg/dl), no ischemia for >4 min (Bruce) 341 patients: 177 PCI, 164 med (80 mg atorvastatin)

15 AVERT Trial: Study Design 341 pts with 1V or 2V CAD (> 50% stenosis) 16% female, mean age 58 years, mean EF 61% High-dose atorvastatin and usual medical therapy n=164 Angioplasty + usual care, including standard lipid lowering n= Months Primary Endpoint: Composite of ischemic events - death, nonfatal MI, CVA, CABG, PCI, or hospitalization due to worsening angina Pitt B et al. N Engl J Med. 1999;341:70-76.

16 AVERT: Time to First Ischemic Event Angioplasty / usual care (n=177) High-dose atorvastatin (n=164) Cumulative incidence (%) P=0.03 Time since randomization (months) Pitt B et al. N Engl J Med. 1999;341:70-76.

17 PCI vs Medical Rx Katritsis DG et al. Circulation. 2005;111:

18 Stable CAD: PCI vs Conservative Medical Management Meta-analysis of 11 randomized trials; N = 2,950 Favors PCI Favors Medical Management P Death Cardiac death or MI Nonfatal MI CABG PCI Risk ratio (95% Cl) Katritsis DG et al. Circulation. 2005;111:

19 COURAGE Design Clinical Outcomes Utilizing Revascularization And Aggressive DruG Evaluation Randomized Clinical Trial stent era PCI + Optimal Medical Therapy vs Optimal Medical Therapy alone Intensive, guideline-driven medical rx and lifestyle intervention in both groups Stable patients with 1-3V CAD amenable to PCI 2287 pts: 1149 PCI + OMT, 1138 OMT 2.5 to 7 year (mean 4.6 year) follow-up Boden W et al., N Engl J Med 356: , 2007

20 Survival Free of Death from Any Cause and Myocardial Infarction 1.0 Optimal Medical Therapy (OMT) (with pci crossover) PCI + OMT Hazard ratio: % CI ( ) P = Number at Risk Years Medical rx PCI

21 Subsequent Revascularization At a median 4.6 year follow-up, 21.1% of the PCI patients required an additional revascularization; 32.6% of the OMT group required a 1 st revascularization 77 patients in the PCI group and 81 patients in the OMT group required subsequent CABG surgery

22 Freedom from Angina During Long-Term Follow-up PCI + OMT OMT p Clinical Angina free Baseline 12% 13% NS 1 Yr 66% 58% < Yr 72% 67%.02 5 Yr 74% 72% NS

23 PCI versus Medical Therapy Large heterogeneity between studies balloon PTCA era (except COURAGE) No mortality benefit in Stable Angina No difference in need for CABG Trend for increase in non-fatal MI in PCI group ~30% increase, mostly peri-pci More subsequent PCI in medical group Less angina in PCI group

24 PCI vs CABG

25 Clinical Randomized Studies CABG vs PTCA RITA (1011) ERACI (127) Lausanne (134) GABI (359) EAST (392) CABRI (1054) MASS (142) BARI (1829) Toulousse (152) CABG vs Stents SIMA (121) ERACI-II (450) ARTS 1 (1205) ARTS II (606) SoS (988) MASS-II (611) AWSOME (454) SYNTAX (1800) BARI 2D (2368) CARDia (600)

26 CABG vs. PCI Meta-Analysis of Late Outcomes Survival MVD Trials Follow-up Favors PTCA Favors CABG # pts #studies 1 year 3 year year 8 year p=0.025 p= Survival Risk Difference (%) Hoffman et al. JACC. 2003;41:

27 CABG vs. PCI Meta-Analysis of Late Outcomes Repeat Revascularization Follow-up Favors PTCA Favors CABG # pts #studies 1 year 3 year 5 year 8 year 2643 (3) 1559 (3) Stent No Stent Revascularization Risk Difference (%) Hoffman et al. JACC. 2003;41:

28 Trials of DES vs CABG in Multivessel CAD Patients ARTS 2 FREEDOM (NIH) SYNTAX (BSI) CARDia (UK & Ireland) VA study (US) (Terminated) COMBAT (CORDIS)

29 ARTS II TRIAL Study Design ARTS II CYPHER Sirolimus Eluting stent N=606 ARTS I R Bare metal stent N= 600 CABG N=605 Primary Endpoint: 1 year MACCE event-free survival with Cypher DES versus CABG MACCE in ARTS 1

30 ARTS II: 1 year MACCE P=NS P=NS P=<0.001 P=0.46 P= % 89.5% 73.7% 88.5% 96.9% 90.7% 92.0% 91.5% 78.1% 95.9% 80% 60% 40% 20% 0% MACCE free survival Survival w/o CVE/MI Survival w/o revasc ARTS II: DES ARTS I: BMS ARTSI: CABG

31 SYNTAX Trial Design 62 EU Sites + 23 US Sites All Heart Pts Team with (surgeon de novo & Total enrollment 3VD interventionalist) and/or LM N=3075 disease (N=4,337) Amenable for both Amenable for only one treatment options Treatment preference (9.4%) treatment approach Randomized Arms N=1800 Stratification: Stratification: LM and Diabetes Referring MD or pts. refused informed LM and consent Diabetes (7.0%) Inclusion/exclusion (4.7%) Two Registry Arms Withdrew before consent (4.3%) Other (1.8%) N=1275 Randomized Arms Two Registry Arms Medical treatment (1.2%) CABG n=1800 TAXUS * CABG PCI vs 2500 N=897 n=897 N=903 n=903 n=1077 N=1077 N= w/ f/u n=198 follow up Non LMDM vs 3VD DM NonDM 71% LM enrolled 5yr f/u no f/u (N=3,075) n=649 n=428 3VD DM 66.3% 28.5% 33.7% 71.5% 28.2% 65.4% 71.8% 34.6% all captured w/ * TAXUS Express

32 Primary Endpoint: 12 Month MACCE Non-inferiority analysis Pre-specified Margin = 6.6% 5.5% +95% CI = 8.3% 0 5% 10% 15% Difference in MACCE 20% The criteria for non-inferiority comparison was not met for the primary endpoint, further comparisons for the LM and 3VD subgroups are observational only and hypothesis generating

33 Outcomes by Syntax Score: 3 Years Kappetein et al EHJ 2011

34 Syntax: Outcomes at 4 Years

35 SYNTAX Trial 5-year f/u results (2013)

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38 Conclusions: PCI versus CABG PCI Decreased procedural morbidity Less likely to have complete revascularization with complex/severe CAD More repeat revascularization Treatment of CTO in question CABG Increased procedural/early risk better long-term outcomes in complex CAD LIMA conduit has demonstrated longevity

39 Guidelines

40 Revascularization to Improve Survival: Left Main CAD Revascularization I IIaIIbIII I IIa IIb III CABG to improve survival is recommended for patients with significant ( 50% diameter stenosis) left main CAD. PCI to improve survival is reasonable as an alternative to CABG in selected stable patients with significant ( 50% diameter stenosis) unprotected left main CAD with: 1) anatomic conditions associated with a low risk of PCI procedural complications and a high likelihood of a good long-term outcome (e.g., a low SYNTAX score [ 22], ostial or trunk left main CAD); and 2) clinical characteristics that predict a significantly increased risk of adverse surgical outcomes (e.g., STS-predicted risk of operative mortality 5%).

41 Revascularization to Improve Survival: Left Main CAD Revascularization I IIaIIbIII I IIaIIbIII PCI to improve survival is reasonable in patients with UA/NSTEMI when an unprotected left main coronary artery is the culprit lesion and the patient is not a candidate for CABG. PCI to improve survival is reasonable in patients with acute STEMI when an unprotected left main coronary artery is the culprit lesion, distal coronary flow is TIMI (Thrombolysis In Myocardial Infarction) grade <3, and PCI can be performed more rapidly and safely than CABG.

42 Revascularization to Improve Survival: Non-Left Main CAD Revascularization CABG I IIaIIbIII PCI I IIaIIbIII CABG or PCI to improve survival is beneficial in survivors of sudden cardiac death with presumed ischemia-mediated ventricular tachycardia caused by a significant ( 70% diameter) stenosis in a major coronary artery.

43 Revascularization to Improve Symptoms I IIaIIbIII I IIaIIbIII CABG or PCI to improve symptoms is beneficial in patients with 1 or more significant ( 70% diameter) coronary artery stenoses amenable to revascularization and unacceptable angina despite GDMT. CABG or PCI to improve symptoms is reasonable in patients with 1 or more significant ( 70% diameter) coronary artery stenoses and unacceptable angina for whom GDMT cannot be implemented because of medication contraindications, adverse effects, or patient preferences.

44 Revascularization to Improve Symptoms I IIa IIb III I IIa IIb III PCI to improve symptoms is reasonable in patients with previous CABG, 1 or more significant ( 70% diameter) coronary artery stenoses associated with ischemia, and unacceptable angina despite GDMT. It is reasonable to choose CABG over PCI to improve symptoms in patients with complex 3- vessel CAD (e.g., SYNTAX score >22), with or without involvement of the proximal LAD artery who are good candidates for CABG.

45 Revascularization to Improve Symptoms I IIa IIb III Harm CABG or PCI to improve symptoms should not be performed in patients who do not meet anatomic ( 50% left main or 70% non left main stenosis) or physiologic (e.g., abnormal fractional flow reserve) criteria for revascularization.

46 Risk Prediction

47 Models of Risk for PCI and CABG Clinical Anatomic Observational registries Duke New York Northern New England Mayo Clinic Randomized trials Balloon PTCA vs. CABG Stent PCI vs. CABG Bare Metal Stent Drug Eluting Stents

48 Angiographic Predictors of Mortality Findings 2vd, 95% LAD 2vd, Prox LAD 3vd, 1>95% 3vd, prox LAD 3vc, 95% Prox LAD Left Main Severe Left main Odds Ratio N=11, Adapted from Dvazik Am Heart J 142:

49 Myocardial Jeopardy Scores Modified APPROACH score BARI score Eu Heart J 2007:28;

50 SYNTAX Score

51 SYNTAX Score

52 PCI Risk Models ACC New York State Northern New England Michigan Cleveland Clinic Foundation Mayo Clinic CADILLAC

53 NCDR Risk Assessment Peterson et al JACC (18) 2010:

54 STS Database Variables 1. Age 15. Multiple Reoperations 2. Aortic Stenosis 16. Myocardial Infarction 3. Body Surface Area 17. Number of Diseased Vessel 4. Cerebrovascular Accident 18. New York Heart Association Class IV 5. Chronic Lung Disease 19. PTCA (< 6 hours) 6. Diabetes/Insulin or Oral 20. PVD, CVA 7. Ejection Fraction 21. Preoperative IABP 8. First Reoperation 22. Racial Designation 9. Hypercholesterolemia 23. Renal Failure, Dialysis 10. Hypertension 24. Shock 11. Immunosuppressive Treatment 25. Status 12. Left Main Disease 13. Male Gender 14. Mitral Insufficiency variables are listed in alpha order to protect the propriety of the STS national database related to variable-specific data

55 Thank You