TRATAMIENTO INVASIVO ENFERMEDAD ISQUEMICA ESTABLE Jonathan Poveda CLINICA BIBLICA 2015
COURAGE
First coronary angioplasty lesion (circles) two days before (A), immediately after (B), and one month after (C) balloon dilation The First Coronary Angioplasty for Stable CAD; 1977
Conventional Wisdom Treatment Assumptions in CAD Management: Patients with symptomatic CAD and chronic angina who have significant coronary stenoses need revascularization Revascularization is required to improve prognosis PCI is less invasive than CABG surgery (i.e., is safer) and, therefore, should be selected
Hypothesis PCI + Optimal Medical Therapy will be Superior to Optimal Medical Therapy Alone
Primary Outcome Death or Nonfatal MI
Secondary Outcomes Death, MI, or Stroke Hospitalization for Biomarker (-) ACS Cost, Resource Utilization Quality of Life, including Angina Cost-Effectiveness
Design Randomization to PCI + Optimal Medical Therapy vs Optimal Medical Therapy alone Intensive, guideline-driven medical therapy and lifestyle intervention in both groups 2.5 to 7 year (mean 4.6 year) followup
Inclusion Criteria Men and Women 1, 2, or 3 vessel disease (> 70% visual stenosis of proximal coronary segment) Anatomy suitable for PCI CCS Class I-III angina Objective evidence of ischemia at baseline ACC/AHA Class I or II indication for PCI
Exclusion Criteria Uncontrolled unstable angina Complicated post-mi course Revascularization within 6 months Ejection fraction <30% Cardiogenic shock/severe heart failure History of sustained or symptomatic VT/VF
Objective Evidence of Ischemia Spontaneous ST-T changes on ECG > 1 mm ST deviation on treadmill test Ischemic imaging defect
Survival Free of Death from Any Cause and Myocardial Infarction 1.0 Optimal Medical Therapy (OMT) 0.9 0.8 0.7 0.6 0.5 0.0 PCI + OMT Hazard ratio: 1.05 95% CI (0.87-1.27) P = 0.62 Number at Risk 0 1 2 3 4 5 6 Years Medical Therapy 1138 1017 959 834 638 408 192 30 PCI 1149 1013 952 833 637 417 200 35 7
Overall Survival 1.0 PCI + OMT 0.9 0.8 0.7 0.6 0.5 0.0 OMT Hazard ratio: 0.87 95% CI (0.65-1.16) P = 0.38 Number at Risk 0 1 2 3 4 5 6 Years Medical Therapy 1138 1073 1029 917 717 468 302 38 PCI 1149 1094 1051 929 733 488 312 44 7
Survival Free of Hospitalization for ACS 1.0 0.9 0.8 OMT PCI + OMT 0.7 0.6 0.5 Hazard ratio: 1.07 95% CI (0.84-1.37) P = 0.56 0.0 Number at Risk 0 1 2 3 4 5 6 Years Medical Therapy 1138 1025 956 833 662 418 236 12 PCI 1149 1027 957 835 667 431 246 13 7
Survival Free of Myocardial Infarction 1.0 0.9 0.8 OMT PCI + OMT 0.7 0.6 0.5 Hazard ratio: 1.13 95% CI (0.89-1.43) P = 0.33 0.0 Number at Risk 0 1 2 3 4 5 6 Years Medical Therapy 1138 1019 962 834 638 409 192 12 PCI 1149 1015 954 833 637 418 200 13 7
Conclusions As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, MI, or other major cardiovascular events when added to optimal medical therapy As expected, PCI resulted in better angina relief during most of the follow-up period, but medical therapy was also remarkably effective, with no between group difference in angina-free status at 5 years
FREEDOM Trial Main Results AHA 2012 November 4, 2012 Los Angeles, CA Valentin Fuster, MD PhD
SYNTAX Trial design: Patients with severe three-vessel or LM disease were randomized to CABG or DES-PCI with paclitaxel-eluting stents. Clinical outcomes were compared at 12 months. Results % 20 15 10 5 0 (p = 0.002) 12.4 17.8 MACCE CABG (n = 897) 20 15 % 10 5 0 p < 0.001) 5.9 13.5 Repeat revascularization DES-PCI (n = 903) MACCE was significantly lower in CABG arm compared with PCI (12.4% vs. 17.8%, p = 0.002), especially for diabetics (p = 0.0025) Significant in the need for repeat revascularization in CABG arm (p < 0.001) Death and MI were similar; CVA with CABG (p = 0.003) Conclusions CABG was associated with fewer repeat revascularizations compared with DES-PCI in patients with LM or three-vessel disease, but a higher rate of stroke No difference in death, MI, or thrombosis Diabetics are especially more likely to benefit with CABG compared with DES-PCI Serruys PW, et al. N Engl J Med 2009;360:961-72
(J Am Coll Cardiol 2013;62:1219 30)
(J Am Coll Cardiol 2013;62:1219 30)
Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial Friedrich W Mohr, MD, Marie-Claude Morice, MD, A Pieter Kappetein, MD, Ted E Feldman, MD, Elisabeth Ståhle, MD, Antonio Colombo, MD, Michael J Mack, MD, David R Holmes, MD, Marie-angèle Morel, BSc, Nic Van Dyck, RN, Vicki M Houle, PhD, Keith D Dawkins, MD and Patrick W Serruys, MD The Lancet Volume 381, Issue 9867, Pages 629-638 (February 2013) DOI: 10.1016/S0140-6736(13)60141-5
Source: The Lancet 2013; 381:629-638 (DOI:10.1016/S0140-6736(13)60141-5) Terms and Conditions
Source: The Lancet 2013; 381:629-638 (DOI:10.1016/S0140-6736(13)60141-5) Terms and Conditions
(J Am Coll Cardiol 2013;62:1219 30)
FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Fractional Flow Reserve Guided PCI versus Medical Therapy in Stable Coronary Disease FAME 2 Clinicaltrials.gov NCT01132495 Bernard De Bruyne, Nico H.J. Pijls, William F Fearon, Peter Juni, Emanuele Barbato, Pim Tonino, for the FAME 2 study group
FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Flow Chart 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, 4, and 5 years
Cumulative incidence (%) FAME 2 : FFR-Guided PCI versus Medical Therapy in Stable CAD Primary Outcomes 30 25 PCI+MT vs. MT: HR 0.32 (0.19-0.53); p<0.001 PCI+MT vs. Registry: HR 1.29 (0.49-3.39); p=0.61 MT vs. Registry: HR 4.32 (1.75-10.7); p<0.001 20 15 10 5 No. at risk MT PCI+MT Registry 0 0 1 2 3 4 5 6 7 8 9 10 11 12 Months after randomization 441 414 370 322 283 253 220 192 162 127 100 70 37 447 414 388 351 308 277 243 212 175 155 117 92 53 166 156 145 133 117 106 93 74 64 52 41 25 13
Nam, C.W. et al. JACC 2011
Original Article Randomized Trial of Stents versus Bypass Surgery for Left Main Coronary Artery Disease Seung-Jung Park, M.D., Young-Hak Kim, M.D., Duk-Woo Park, M.D., Sung-Cheol Yun, Ph.D., Jung-Min Ahn, M.D., Hae Geun Song, M.D., Jong-Young Lee, M.D., Won- Jang Kim, M.D., Soo-Jin Kang, M.D., Seung-Whan Lee, M.D., Cheol Whan Lee, M.D., Seong-Wook Park, M.D., Cheol-Hyun Chung, M.D., Jae-Won Lee, M.D., Do-Sun Lim, M.D., Seung-Woon Rha, M.D., Sang-Gon Lee, M.D., Hyeon-Cheol Gwon, M.D., Hyo-Soo Kim, M.D., In-Ho Chae, M.D., Yangsoo Jang, M.D., Myung-Ho Jeong, M.D., Seung-Jea Tahk, M.D., and Ki Bae Seung, M.D. N Engl J Med Volume 364(18):1718-1727
Cumulative Incidence of the Primary End Point of Major Adverse Cardiac or Cerebrovascular Events in the Two Study Groups. Park S-J et al. N Engl J Med 2011;364:1718-1727
Cumulative Incidence of Death from Any Cause, Myocardial Infarction, or Stroke in the Two Study Groups. Park S-J et al. N Engl J Med 2011;364:1718-1727
Clinical End Points. Park S-J et al. N Engl J Med 2011;364:1718-1727
Conclusions In this randomized trial involving patients with unprotected left main coronary artery stenosis, PCI with sirolimus-eluting stents was shown to be noninferior to CABG with respect to major adverse cardiac or cerebrovascular events. However, the noninferiority margin was wide, and the results cannot be considered clinically directive.
Original Article Randomized Trial of Preventive Angioplasty in Myocardial Infarction David S. Wald, M.D., Joan K. Morris, Ph.D., Nicholas J. Wald, F.R.S., Alexander J. Chase, M.B., B.S., Ph.D., Richard J. Edwards, M.D., Liam O. Hughes, M.D., Colin Berry, M.B., Ch.B., Ph.D., Keith G. Oldroyd, M.D., for the PRAMI Investigators N Engl J Med Volume 369(12):1115-1123 September 19, 2013
Enrollment and Follow-up. Wald DS et al. N Engl J Med 2013;369:1115-1123
Kaplan Meier Curves for the Primary Outcome. Wald DS et al. N Engl J Med 2013;369:1115-1123
Details Regarding PCI and Medical Therapy at Discharge. Wald DS et al. N Engl J Med 2013;369:1115-1123
Wald DS et al. N Engl J Med 2013;369:1115-1123 Prespecified Clinical Outcomes.
Conclusions In patients with STEMI and multivessel coronary artery disease undergoing infarct-artery PCI, preventive PCI in noninfarct coronary arteries with major stenoses significantly reduced the risk of adverse cardiovascular events, as compared with PCI limited to the infarct artery.
ENFERMEDAD MULTIVASO EHJ 2011; 32:2125-34
FREEDOM Design (1) Eligibility: DM patients with MV-CAD eligible for stent or surgery Exclude: Patients with acute STEMI Randomized 1:1 MV-Stenting With Drug-eluting CABG With or Without CPB All concomitant Meds shown to be beneficial were encouraged, including: clopidogrel, ACE inhib., ARBs, b-blockers, statins
MYOCARDIAL INFARCTION Myocardial Infarction, % 30 20 10 PCI/DES CABG Logrank P<0.0001 PCI/DES 13.9 % 6.0% CABG 0 0 1 2 3 4 5 Years post-randomization PCI/DES N 953 853 798 636 422 220 CABG N 947 824 772 629 432 229
All-Cause Mortality, % ALL-CAUSE MORTALITY 30 PCI/DES CABG 20 Logrank P=0.049 PCI/DES 10 CABG 0 5-Year Event Rates: 16.3% vs. 10.9% 0 1 2 3 4 5 Years post-randomization PCI/DES N CABG N 953 897 845 685 466 243 947 855 806 655 449 238
Stroke, % STROKE 30 20 Severely Disabling Scale CABG PCI/DES NIH > 4 55% 27% Rankin >1 70% 60% CABG PCI/DES Logrank P=0.034 10 CABG 5.2% 0 PCI/DES N CABG N PCI/DES 2.4% 0 1 2 3 4 5 Years post-randomization 953 891 833 673 460 241 947 844 791 640 439 230
Repeat Revascularization, % REPEAT REVASCULARIZATION 30 PCI/DES CABG Log rank P<0.0001 20 13% 10 PCI/DES 5% 0 CABG 0 1 2 3 4 5 6 7 8 9 10 11 12 Months post-procedure PCI/DES N 944 887 856 818 792 CABG N 911 858 836 825 806
Freedom from Event (%) Freedom from Event (%) Freedom from Event (%) 100 90 80 70 60 50 40 30 20 10 0 PRIMARY ENDPOINT DEATH / STROKE / MI TREATMENT / SYNTAX INTERACTION - SYNTAX Score 22 (N=669) 5-Year Event Rates: 23.2% 17.2% PCI/DES CABG p=0.58 100 90 80 70 60 50 40 30 20 10 0 SYNTAX Score 23-32 (N=844) 5-Year Event Rates: 27.2% 17.7% PCI/DES CABG 0.0 1.0 2.0 3.0 4.0 5.0 Years post-randomization 0.0 1.0 2.0 3.0 4.0 5.0 Years post-randomization 100 90 80 70 60 50 40 30 20 10 0 SYNTAX Score 33 (N=374) 5-Year Event Rates: 30.6% 22.8% PCI/DES CABG 0.0 1.0 2.0 3.0 4.0 5.0 Years post-randomization
SUBGROUP ANALYSES CABG Worse PCI/DES Worse Treatment x Subgroup Interaction 5-yr Rate (%) PCI/DES CABG ALL SUBJECTS 1900 SYNTAX 22 669 SYNTAX 23-32 844 SYNTAX 33 374 Males 1356 Females 544 Caucasian 1452 African-American 119 2-Vessel Disease 314 3-Vessel Disease 1573 LVEF < 40% 32 LVEF 40% 1259 No LAD involved 151 LAD involved 1737 Hx stroke 65 No Hx stroke 1835 Renal insuff. 129 No Renal insuff. 1771 HbA1c < 7% 630 HbA1c 7% 1119 N. American Site 770 Non-N. American 1130 P=0.58 P=0.46 P=0.55 P=0.75 P=0.37 P=0.83 P=0.57 P=0.62 P=0.99 P=0.049 27 19 23 17 27 18 31 23 27 18 26 21 27 19 24 16 22 11 27 20 62 31 23 18 23 18 27 19 59 35 25 18 44 37 25 17 23 16 28 20 28 16 25 21 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 Hazard Ratio for Death/Stroke/MI