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 CAD Trial Year in Review Incremental Impact of PCI ACS Prevention DAPT CULPRIT HOPE-3 ABSORB II/III MATRIX DANAMI-3 Chest Pain Choice TUXEDO LEADERS-FREE RIDDLE-NSTEMI PEGASUS IMPROVE-IT STICH 10-Year SPRINT Early BAMI AVOID Research PCSK9 PROCAT II TOTAL New ACCELERATE COSIRA CAD Trial Year in Review Incremental Impact of PCI ACS Prevention DAPT CULPRIT HOPE-3 ABSORB II/III MATRIX DANAMI-3 Chest Pain Choice TUXEDO LEADERS-FREE RIDDLE-NSTEMI PEGASUS IMPROVE-IT STICH 10-Year SPRINT Early BAMI AVOID Research PCSK9 PROCAT II TOTAL New ACCELERATE COSIRA CAD Trial Year in Review Incremental Impact of Don’t Maybe AVOID CULPRIT Early BAMI MATRIX HOPE-3 ABSORB II/III COSIRA LEADERS-FREE ACCELERATE STICH 10-Year SPRINT PEGASUS DAPT IMPROVE-IT PCSK9 PROCAT II DANAMI-3 Research Do TOTAL TUXEDO New RIDDLE-NSTEMI Chest Pain Choice l~I l~I ~~~~~~~o_n_rr._,_rN_A_1_.A_R_T_1c_,n_.F ~~~~~~~o_n_rr._,_rN_A_1_.A_R_T_1c_,n_.F~~~~~~ '11 Randomized Trial of Primary PCI with or without Routine Manual Thrombectomy S.S:.Jal1y; JA ~·ms, S YLl5l.lf; 16 Meeks L Th.lb.ii~ G Stanlu:rwic., J Pogue, M J Rc,'kaoss, S Ki::t:b, R Mc.r 79 (adapted per 40 mg FDA label 2011) 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 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 admission for UA, LDL-C and Lipid Changess Yr Mean ' LDL-C TC TG HDL Simva 69.9 145.1 137.1 48.1 EZ/Simva 53.2 125.8 120.4 48.7 Δ in mg/dL -16.7 -19.3 -16.7 +0.6 hsCRP 3.8 3.3 -0.5 Media n Time avg 69.5 vs 53.7 mg/dL ce r EZ/Simva Simva zatio mo 8990 8889 8230 7701 7264 6864 6583 6256 5734 5354 4508 3484 2608 1078 9009 8921 8306 7843 7289 6939 6607 6192 5684 5267 4395 3387 2569 1068 Primary Enddpoint ITT —- ' Cardiovascular death, MI, documented unstable angina requiring rehospitalization, coronary revascularization (≥30 HR 0.936 CI (0.887, 0.988) days), or stroke Simva — 34.7% p=0.016 2742 events NNT= 50 EZ/Simva — 32.7% 2572 events w T es ce a z o (yea s) 7-year event rates Individual Cardiovascular Endpoints and CVD/MI/Stroke HR Simva* EZ/Simva* p-value All-cause death 0.99 15.3 15.4 0.782 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 0.79 4.1 3.4 0.008 0.95 23.4 21.8 0.107 1.06 1.9 2.1 0.618 0.90 22.2 20.4 0.003 Ischemic stroke Cor revasc ≥ 30d UA CVD/MI/stroke 0.6 1.0 Ezetimibe/Simva Better 1.4 Simva Better *7-year event rates (%) ConeclI usiioonnss ' First triall demonstratiinngg iincrementtaall cliniiccaall benefit when adding a non-stattiinn agent ((ezeettiimibe)) to statin therapyy:: Lowering LLDL-C with ezetimiibe rreduces CV events Even LLower iis Even Better ((achieved mean LDL-C 53) Reduced subsequennUt/totall number of events Further support of the benefit lliippidid therapy of continuuaattiioonn of after a rrecurrentt on symptoms, iinttensive morbidity, prognoossiiss and cost CV event Confirms ezetimiibe safety profile - no excess myopathy or CA IImplications Reaaffffirm LDL hypothesiiss:: rreduciingg LDL rreduces CV events s Impact of LDL Lowering Lower is Better Wright and Murphy NEJM 2016:362-4 Impact of LDL Lowering Relative Risk Reduction Silverman, et Across Classes al JAMA 2016;316(12):1289-1297 Immediate Versus Delayed Invasive Intervention for Non-STEMI Patients The RIDDLE-NSTEMI Study Alek3.mtka!Milo2vic, MD ""' Zoran a V.isifieviic-Pt:ikr.ijciic.}/[I) IPn0.cDej.m Milmn.4,ic.Ml!).• k:151.i M:ui:nkcrvir.P111D."'~ '\lil11da.1J Vw:Cl!!,.ic Miil),, Piii'), -En:rwl::rv Slehnmoiir lID PtiD.""""' lt.ffiib Jismim !Ml!),, Pi1D.~""' 11.fil!ldrag l)itic., }/[I)_" Sanj~ :S1.tr.il:IJ!,IK l\nD.• Gma11 Sbn llcrvir Ml), IPnD""' OBJECTIVES llm '1lE)' •imedl1D • ,,, ih,,di,i:c,I i ,t of immedi•te """'"'d~ed ~nt,,rv,ention,in pili ,t.,,rilh -.-5f-sc,gm ,t "'1""•rdial in• rtic111(1"51EMI) CONCLUSIONS lm lmmediat,e Ml compared with th risk of new Ml in the Patients Patients invasive strategy in NSTEMI e delayed College of Cardiology College of Cardiol is associated with lower rates of death or new invasive strategy at early and midterm follow-up, mainly due to a pra-cathetarizatlon [RIDDLE-NSTEMI]; [RIDDLE-NS patients period (Immediate NCT02419833) decrease Versus Del.ayed Invasive Intervention (J Am Coll Cardiol lntv for Non-STEMI © 2016 by the 2016;9:541-9) Foundation iirtava: ,0.17 ID O,.i.7, p - !l.!002} Tht: obH:no!!il rHlll.ts wl!f• mairal:), lll:ldJu~•ble ~a, the DCcurr,,enc,e cf new· Ml i111 lme Pf1!-c;1th1tei:z,;rtioo pll!riod (0 wtli1 "* Ml15 in lme d~·irrtawlltia,n '!jfc;!llp) Jhe nt~ DI r 11:n, 1"11!'111' 1111! iltEll!du.te-mtm,,1e1mcmi t.O, or recurrent ischemu irtfflledial:., ,tel"\!mtion ;roup 11 both 30 d~~ (6 &"' ¥s 26 ?1!1 p ; O.Oll1) •oo w;is + 1Ct grcup vs, I ~111 !Mis in IDIHI" in lhl! , - (1S.4W = l3-1,tl; p ,e; (UlM) CONCI.USIONS irrun!dilte ir.rnwe l'lr.JkW in N!:'JEMI p,itimts is zsoo.ia.~ed v.ilh lcwer rl'l:e; d dml.b er new risk of I.II cmnp.1rm with lhil! de~ in'r.lsive m:r~ :rt ,e.t, ,mil midbm'n ~qi main\' d\r 1D I Ml'GSil! in !lie ,_Niil lknm !'.le!~ llll'i'~ P.1.1islt~ [llllOOL.E:-N!ilEta.11]: fa Moo-STEMI NC'.TCt2.-1~l.l) (J Am C.CU ,C,arci::il ln!Y ::!016;9:5,U~) ~ 201:€ hf the 1r.w !Ml in ·tilt! FR-t::.a'lnc1rriz.ttion, perm Clmmr;:lia.~e- Americ:ai O:illege of C'.udi001!J1 ~oon&:tion ['[Jcaa•I}' syndJ-om., ,CNSTf-JiCS),, ,tr.r.tr:,gy i• fa¥omd avce• moen! (1-7), but In• i=e- I aa i ::f,eemio: ,, ,,,,, · -hit.- w.:rlliag to p•llform an inv;o,ri, , in-.,ci= oo:n.2.r,·ati,,., rmm;o;g ,• of" optimcal limia,i; ,.,,mains n pa!01enb, wilihJ aaa-ST-2eg1ms1t eil""'; oti.on.,oa:rrt:c procedure teal, indiate- intcr.,,entiaa 6o:r 11unlarhlr i;ilJL140) 0.25 Delayed** High Risk Cumulative Hazard 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 Peak Troponin I 16 ACS * 13.7 14 30-Day MACE 12 30-Day Major Bleeding 10.2 10 6.8 4 2.1 1.7 Immediate (Mean 70 Min) Delayed (Mean 21 Hrs) *Primary Endpoint n=352 All p=NS Montalescot, et al JAMA 2009;302:947 RIDDLE-NSTEMI Mean 1.4 hrs Mean 61 hrs RIDDLE-NSTEMI Immediate ( 140 Cardiol Intv 2016 Early Invasive vs Ischemia-Guided Strategy Selection Factors and Timing Summary What Is Clarification of the Impact? 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, Rochester, MN CAM ON barsness.gregory@mayo.edu CP1124540-1