15th National Congress of Cardiology Hanoi, Vietnam, October 9-11, 2016 Coronary Artery Diseases Year in Review 2015-2016 Five Trials That Will Impact Patient Care Gregory W Barsness, MD, FACC, FAHA, FSCAI Consultant, Internal Medicine & Cardiology and Radiology Director, Mayo Clinic EECP Laboratory Director, Mayo Clinic Cardiac Intensive Care Unit Mayo Clinic College of Medicine Rochester, MN, USA Nothing to Disclose Related to this Talk CAD Trial Year in Review Incremental Impact of New Research PCI ACS Prevention DAPT CULPRIT HOPE-3 ABSORB II/III DANAMI-3 IMPROVE-IT MATRIX Chest Pain Choice PCSK9 TUXEDO PROCAT II STICH 10-Year LEADERS-FREE TOTAL SPRINT RIDDLE-NSTEMI Early BAMI COSIRA PEGASUS AVOID ACCELERATE CAD Trial Year in Review Incremental Impact of New Research PCI ACS Prevention DAPT CULPRIT HOPE-3 ABSORB II/III DANAMI-3 IMPROVE-IT MATRIX Chest Pain Choice PCSK9 TUXEDO PROCAT II STICH 10-Year LEADERS-FREE TOTAL SPRINT RIDDLE-NSTEMI Early BAMI COSIRA PEGASUS AVOID ACCELERATE CAD Trial Year in Review Incremental Impact of New Research Don’t Maybe Do AVOID CULPRIT HOPE-3 Early BAMI ABSORB II/III IMPROVE-IT MATRIX COSIRA PCSK9 TOTAL PROCAT II STICH 10-Year TUXEDO LEADERS-FREE SPRINT DANAMI-3 PEGASUS Chest Pain Choice ACCELERATE DAPT RIDDLE-NSTEMI Thrombus Aspiration in PPCI Meta-Analysis of Mortality Adjunctive device prior to PCI 5.3 P = 0.018 4.4 Mortality (%)* PCI alone P = 0.050 I IIa IIb III 2.7 3.1 2.8 3.4 Manual thrombus aspiration Bavry AA, et al Eur Heart J 2008 Mechanical thrombectomy Embolic protection *Weighted Mean 5.0 months TOTAL Trial Flow and Adherence 10,732 enrolled and randomized 10,066 underwent PCI for STEMI 5033 Manual Thrombectomy Crossover to PCI alone in 230 (4.6%) 5033 included in analysis TOT AL 5030 PCI Alone Cross-over to Thrombectomy as initial strategy in 69 (1.4%) Bailout Thrombectomy in 355 (7.1%) 5030 included in analysis Jolly et al Lancet 2015 Higuma JACC Card Int 2016;8:2002 Jolly et al Lancet 2015 2013 ACC/AHA STEMI Guideline Thrombus Aspiration in PPCI Manual aspiration thrombectomy is reasonable for patients undergoing PPCI I IIa IIb III Study Design Patients stabilized post ACS ≤ 10 days LDL-C 50–125*mg/dL (or 50–100**mg/dL if prior lipid-lowering Rx) N=18,144 *3.2mM **2.6mM Standard Medical & Interventional Therapy Simvastatin 40 mg Uptitrated to Simva 80 mg if LDL-C > 79 (adapted per FDA label 2011) Ezetimibe / Simvastatin 10 / 40 mg Follow-up Visit Day 30, every months 90% power to detect ~9% difference Duration: Minimum ½-year follow-up (at least 5250 events) Primary Endpoint: CV death, MI, hospital admission for UA, coronary revascularization (≥ 30 days after randomization), or stroke Cannon CP AHJ 2008;156:826-32; Califf RM NEJM 2009;361:712-7; Blazing MA AHJ 2014;168:205-12 LDL-C and Lipid Changes Yr Mean LDL-C TC TG HDL hsCRP Simva 69.9 145.1 137.1 48.1 3.8 EZ/Simva 53.2 125.8 120.4 48.7 3.3 Δ in mg/dL -16.7 -19.3 -16.7 +0.6 -0.5 Median Time avg 69.5 vs 53.7 mg/dL Primary Endpoint — ITT Cardiovascular death, MI, documented unstable angina requiring rehospitalization, coronary revascularization (≥30 days), or stroke HR 0.936 CI (0.887, 0.988) p=0.016 Simva — 34.7% 2742 events NNT= 50 EZ/Simva — 32.7% 2572 events 7-year event rates Individual Cardiovascular Endpoints and CVD/MI/Stroke All-cause death HR 0.99 CVD 1.00 6.8 6.9 0.997 CHD 0.96 5.8 5.7 0.499 MI 0.87 14.8 13.1 0.002 Stroke 0.86 4.8 4.2 0.052 Ischemic stroke 0.79 4.1 3.4 0.008 Cor revasc ≥ 30d 0.95 23.4 21.8 0.107 UA 1.06 1.9 2.1 0.618 CVD/MI/stroke 0.90 22.2 20.4 0.003 0.6 Ezetimibe/Simva Better 1.0 1.4 Simva Better Simva* EZ/Simva* p-value 15.3 15.4 0.782 *7-year event rates (%) Conclusions First trial demonstrating incremental clinical benefit when adding a non-statin agent (ezetimibe) to statin therapy: Lowering LDL-C with ezetimibe reduces CV events Even Lower is Even Better (achieved mean LDL-C 53) Reduced subsequent/total number of events Further support of the benefit of continuation of intensive lipid therapy after a recurrent CV event Implications on symptoms, morbidity, prognosis and cost Confirms ezetimibe safety profile - no excess myopathy or CA Reaffirms LDL hypothesis: reducing LDL reduces CV events Impact of LDL Lowering Lower is Better Wright and Murphy NEJM 2016:362-4 Impact of LDL Lowering Relative Risk Reduction Across Classes Silverman, et al JAMA 2016;316(12):1289-1297 Timing of Intervention in ACS (TIMACS) Early (36) Kaplan-Meier Cumulative Risk of the Death, MI or Stroke Stratified by Baseline GRACE Risk Score: Low (≤140) vs High Risk (>140) 0.25 Delayed** Cumulative Hazard High Risk Early* I IIa IIb III 0.00 90 180 Days *Early intervention (med 14 hrs) Mehta SR et al NEJM 2009;360:2165-2175 **Delayed intervention (med 50 hrs) ABOARD Immediate vs Delay Angio in High-Risk ACS Peak Troponin I * 30-Day MACE 30-Day Major Bleeding 16 13.7 14 12 10.2 10 6.8 4 2.1 1.7 Immediate (Mean 70 Min) *Primary Endpoint n=352 All p=NS Delayed (Mean 21 Hrs) Montalescot, et al JAMA 2009;302:947 RIDDLE-NSTEMI Mean 1.4 hrs Mean 61 hrs RIDDLE-NSTEMI Immediate ( 140 Milosivec, et al J Am Coll Cardiol Intv 2016 Early Invasive vs Ischemia-Guided Strategy Selection Factors and Timing Summary What Is the Impact? Clarification of what not to in STEMI: No Routine thrombus aspiration No Delayed stent implantation Incomplete guidance on complex issues: Attempt complete revascularization in patients with STEMI (timing uncertain) Enhanced knowledge of what to in ACS: LDL-lowering hypothesis is alive! Prompt PCI in NSTE-ACS (akin to STEMI) Mayo Clinic Rochester, MN CAM ON barsness.gregory@mayo.edu CP1124540-1