PCI for Stable Ischemic Heart Disease: What Happened in the Last Week?

Transcription

1 PCI for Stable Ischemic Heart Disease: What Happened in the Last Week? Ajay J. Kirtane, MD, SM Center for Interventional Vascular Therapy Columbia University Medical Center / NewYork Presbyterian

2 Disclosure Statement of Financial Interest Ajay J. Kirtane Institutional grants to Columbia University and/or Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical

3 Last Thursday Morning (at TCT)

4 Objective Randomised Blinded Investigation with optimal medical Therapy of Angioplasty in stable angina (ORBITA) Rasha Al-Lamee, MA (Oxon) MB BS MRCP Imperial College London

5 Inclusion criteria Stable angina One or more 70% stenosis in a single vessel Suitable for PCI

6 Randomization Trial design Enrolment assessment CCS SAQ EQ-5D-5L MEDICAL OPTIMIZATION PHASE Prerandomization assessment CCS SAQ EQ-5D-5L Exercise test Stress echo Blinded procedure Research angiogram: ifr, FFR Sedation PCI BLINDED FOLLOW UP PHASE Follow-up Assessment CCS SAQ EQ-5D-5L Exercise test Stress echo Placebo Six weeks Six weeks

7 ORBITA trial 230 enrolled Dec Jul 2017 in 5 UK sites Medical optimization phase 30 patients exited 200 patients randomized PCI (n=105) Placebo (n=95) Blinded follow-up phase 4 patients did not complete follow-up Follow-up (n=105) Follow-up (n=91)

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9 Number of antianginal drugs Medical therapy optimization PCI Placebo % 1.90% 12.40% 13.30% 24.80% 22.90% 31.60% 2.10% 23.20% 4.20% 5.30% 18.90% % 38.90% % 63.80% 74.70% 71.60% 24.20% % 1.00% Enrolment Pre-randomization Follow-up 5.30% Enrolment Pre-randomization Follow-up

10 Stenosis severity Area stenosis by QCA (%) Area stenosis by QCA (%) PCI PCI n = (SD ) (SD 10.2) Placebo Placebo n = (SD ) (SD 10.3) P FFR FFR (SD 0.16) (SD 0.16) (SD 0.16) (SD 0.16) ifr ifr (SD 0.22) (SD 0.22) (SD 0.21) (SD 0.21)

11 Change in exercise time (seconds) Primary endpoint result Change in total exercise time (SD 86.3) p=0.001 PCI 11.8 (SD 93.3) p=0.235 Placebo Error bars are standard errors of the mean

12 Change in exercise time (seconds) Primary endpoint result Change in total exercise time (SD 86.3) p= sec (-8.9 to 42.0) p= PCI 11.8 (SD 93.3) p=0.235 Placebo Error bars are standard errors of the mean

13 Secondary endpoint results Blinded evaluation of ischaemia reduction Peak stress wall motion index score PCI n = 80 Placebo n = 57 Pre-randomization 1.11 (0.18) 1.11 (0.18) Follow-up Δ (Pre-randomization to follow-up) Difference in Δ between arms 1.03 (0.06) (0.17) p< (0.19) 0.02 (0.16) p= (-0.15 to -0.04) p=0.0011

14 Secondary endpoint results: Quality of Life Scores PCI Placebo Baseline 6 weeks Baseline 6 weeks SAQ Physical Limitation SAQ Anginal Frequency SAQ Angina Stability Bold values represent significant changes from baseline No between-group differences between arms were detected

15 Secondary endpoint results CCS class improved in both groups CCS class at enrolment CCS class at prerandomization CCS class at followup CCS IV 37% 40% 24% 33% 0% 1% 12% 16% CCS III 35% 34% CCS II CCS I CCS 0 61% 57% 2% 3% PCI Placebo 53% 14% 9% PCI 43% 11% 14% Placebo 13% 39% PCI 20% 29% Placebo

16 ORBITA Results Summary PCI relieved hemodynamic significance of stenoses by physiologic criteria and relieved ischemia by DSE (placebo did not) Exercise time increased by +28 seconds in PCI arm (but not significantly in placebo arm: +12 seconds) Difference between arms (16 seconds) was not significant Most QoL Measures were no different between arms but improved in both (slightly greater with PCI)

17 The implications of ORBITA are profound and farreaching. First and foremost, the results of ORBITA show unequivocally that there are no benefits for PCI compared with medical therapy for stable angina, even when angina is refractory to medical therapy. Based upon these data, all cardiology guidelines should be revised to downgrade the recommendation for PCI in patients with angina despite medical therapy.

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19 Two Goals of Therapy in Patients with Stable CAD 1. Improve Symptoms and Quality of Life Measured by soft endpoints (i.e. angina/qol scales) 2. Improve Prognosis Measured by hard endpoints (i.e. death, MI)

20 Appropriateness of Revascularization and Outcomes in the UK Studies using [the RAND] method have shown that overuse of invasive techniques in the management of coronary disease is uncommon, and attention has turned to the issue of underuse Angina at 1 year Hemingway et al. NEJM 2001

21 COURAGE: Effect of Medical Therapy SAQ Freedom From Angina PCI + OMT OMT p Baseline 21% 23% NS 3 Months 53% 42% < Year 57% 50% Years 59% 53% Years 59% 56% NS Minimal DES Use and 32% of Medically Treated Patients in the Trial Crossed Over to PCI Weintraub et al, NEJM 2008

22 Freedom from Anti-anginal Meds Despite 32% XO to PCI in the OMT group PCI + OMT compared to OMT resulted in: Significantly less use of nitrates at: - 1 year (53% vs. 67%) - 3 years (47% vs. 61%) - 5 years (40% vs. 57%) Significantly less use of Ca +2 channel blockers at: - 1 year (40% vs. 49%) - 3 years (43% vs. 50%) - 5 years (42% vs. 52%) Boden WE et al. NEJM 2007;356:

23 Crossover Rate COURAGE: Cross-Overs from OMT Arm 50% 45% 40% 35% 30% 25% 20% 15% 10% 5% 0% daily weekly monthly none Baseline SAQ Angina Frequency Score In a matched analysis, MT with 1 st yr x-over was not associated with death, MI, or SAQ but was associated with worse health status and unstable angina admissions (OR 2.78, 95% CI [1.1,7.5], p=0.04) J. Spertus et al, TCT 2010 and Circ CV Qual Outcomes 2013

24 Cumulative Incidence of Worsening Angina: BARI 2D Additionally, among patients with angina at baseline, freedom from angina after randomization was higher among revascularized patients compared to medical therapy Dagenais et al, Circulation 2011

25 FAME-2: Stable CAD patients scheduled for 1, 2 or 3 vessel DES-PCI N = 1220 Randomized Trial FFR in all target lesions Registry At least 1 stenosis with FFR 0.80 (n=888) When all FFR > 0.80 (n=332) Randomization 1:1 PCI + MT 73% MT 27% MT 50% randomly assigned to FU Follow-up after 1, 6 months, 1, 2, 3 and 5 years

26 % with CCS II-IV Angina FAME-2: Quality of Life % of Patients with Class II-IV Angina at each Time Point

27 FAME-2: Quality of Life Mean Number of Antianginal Medications/Patient at each Time Point

28 Results: Clinical Outcome Three Year Rate of Death, MI, or Urgent Revascularization

29 Results: Clinical Outcome Three Year Rate of Death, MI, or Urgent Revascularization *P value compares PCI + MT patients with MT patients

30 FAME-2: Costs

31 Key Characteristics of the ORBITA Population Single vessel disease ~30% FFR negative But angiographically legitimate (real-world practice) Intense medical therapy prior to randomization At randomization, patients symptoms were well-controlled as assessed by SAQ Approximately monthly angina Good exercise tolerance by VO2Max Minimal ischemia by DSE and DTS

32 Algorithm for GDMT for SIHD

33 SYNTAX: Generic QOL and Utilities 55 SF - 36 Physical Component Summary SF - 36 Mental Component Summary P<0.001 P=0.50 P=0.07 P<0.001 P=0.23 P= Baseline 1 month 6 months 12 months 30 Baseline 1 month 6 months 12 months 1 EQ - 5D Utilities (US) PCI 0.9 CABG P<0.001 P=0.16 P=0.99 Quality Adjusted Life Years D = 0.02 (P<0.01) 0.5 Baseline 1 month 6 months 12 months SYNTAX 3VD 5-year Outcomes TCT 2012 Mohr 23 October 2012 Slide 60 Cohen DJ et al. NEJM 2011;364:

34 Quality of Life Angina frequency, physical limitations, and quality-of-life domains of the SAQ assessed at baseline, at 1, 6, and 12 months, and annually thereafter. SAQ Angina Frequency SAQ Physical Limitations SAQ Quality of Life Adjusted: * P<0.05 favoring PCI *P<0.05 favoring CABG Abdallah MS et al. JAMA 2013;on-line

35 SAQ-Angina Frequency 100 PCI CABG Δ = 1.5 p = 0.03 Δ = -0.3 p = Months Δ = -0.8 p = 0.21 Baron et al, JACC 2017

36 1: n=5 2: n=5 3: n=13 4: n=8 5: n=8 6: n=7 7: n=5 8: n=14 9: n=7 10: n=6 11: n=8 12: n=5 13: n=5 14: n=15 15: n=18 16: n=21 17: n=8 18: n=6 19: n=9 20: n=5 21: n=15 22: n=6 23: n=15 24: n=6 25: n=6 26: n=7 Rates of Under-recognition APPEAR: Under-recognition of Angina Individual Physician Reporting compared with SAQ 100% 80% 60% 40% 20% 0% Physicians in APPEAR: Number of Patients Seen Arnold, S. et al. Circ Cardiovasc Qual Outcomes. 2016; 9:00-00

37 How Do Our Patients with Real Symptoms Actually Feel After Revascularization?

38 GDMT vs. Revasc for Stable Ischemic Heart Disease Factors favoring GDMT Factors favoring Revasc + GDMT Symptoms: Exercise capacity: Ischemia/Risk: Anti-anginal drug tolerance: Revasc. risk (pt factors, cor anat): DAPT compliance: None to mild Normal None to mild Good High Poor Moderate to severe Reduced Moderate to severe Poor Low Good Adapted from G. Stone

39 An It Unnecessary wasn t their Procedure? LAD! * This is really American medicine at its worst - Steven Nissen He is the poster child for the inappropriate use of stenting - David Brown *G. W. Bush, CRT 2014