Update in CAD: “To Stent or not to Stent: is that the real question?” Gustavo R. Heudebert, MD Division of General Internal Medicine Road Map Background Information Medical therapy or revascularization? Which stent is better/safer? Matching stents to patients Long term management of DES Case#1 A 55 year old male non diabetic with stable angina has noticed chest pain with less exercise but not at rest. No other symptoms. BP 138/62. BMI of 29. Rest of PE unchanged. EKG without any new changes. LDL is 94 mg/dl. No tobacco use. Sedentary. Would you refer for LHC and possible PCI? Case #2 A 62 year old female with known CAD comes for a routine follow-up visit. She has T2DM, HTN, and is a former smoker. She had a PCI to the LCx (DES) 12 months ago and is doing well. Her medications include metformin, a beta blocker, ASA, clopidogrel, and an ACE-I. What further recommendations do you have regarding her anti-platelet therapy? Background Most common cause of death in the US Most costly diagnosis One in five Americans have CAD by age 70 Lifetime risk (at age 40) Males: 49% Females: 32% Mortality is falling Background Clinical presentation Acute Coronary Syndrome Chronic Stable Angina Silent Ischemia Management Medical Management Medications, lifestyle modifications Revascularization PCI and CABG Terminology of Angina Stable angina Angina that occurs predictably and reproducibly at the same level with exercise and is relieved with rest or nitroglycerin. Unstable angina A variety of clinical conditions including the new onset of chest pain, rest angina, an accelerating pattern of previously stable angina, post- myocardial infarction (MI) angina, and angina after a revascularization procedure Angioplasty Story First deployed in 1977 Very high risk of re-stenosis Improved with use of aspirin Stents Bare metal: approved by FDA in 1994 Less re-stenosis Further improved by thienopyridines Drug Eluting: introduced in 2003 DES Story Polymer coated stent with anti-proliferative agents (sirolimus and paclitaxel) Approved by FDA in 2003 and 2004 80% of all stents deployed by 2005 Indications Stable coronary artery disease Lesions up to 32 mm in length Untreated native vessels Ongoing data collection mandated by FDA Definitions Stent Thrombosis “Angiographic vessel occlusion and/or a STEMI in the target vessel distribution” Timing Acute: within 24 hours Subacute: within 30 days Late: 30 days to one year Very Late: greater than one year “Optimal Medical Therapy with or without PCI for Stable Coronary Artery Disease” NEJM 2007; 356:1003-16. Methods Sponsored by DVA/VAMC Patients with stable CAD or stabilized CCS Class IV angina > 70% epicardial vessel (at least one vessel) Objective evidence of ischemia Excluded Persistent Class IV symptoms, EF <30%, poor exercise stress test, refractory HR or shock Interventions / Outcomes Random assignment PCI Vs. medical therapy Antiplatelets, lipid lowering therapy, anti-angina, and ACE or ARB Most patients received bare metal stents (BMS) Primary Outcome: death of any cause and non fatal AMI Secondary Outcomes: composite of death, AMI, CVA, and hospitalization for UA with positive markers Analyses Expected event rates: PCI (16.4%) and medical (21%) Incorporated dropout and crossover 2270 patients Intention to treat Survival analyses Kaplan-Meier, Cox Proportional Hazards Results 2287 enrolled (1149 in PCI; 1138 medical) 2/3 with multivessel CAD 95% with objective ischemia 60% with CCS Class II or II angina Median follow-up of 4.6 years 9% lost of follow-up Revascularization (21% Vs 32%) Approximately 72% angina free Summary Optimal medical therapy has similar outcomes to PCI based strategy as initial management of patients with stable coronary artery disease. Less revascularization with PCI Unknowns DES based PCI Prolonged use of anti-platelets “Safety and Efficacy of Sirolimus- and Paclitaxel-Eluting Coronary Stents” NEJM 2007;356:998-1008. Methods Pooled analyses from: Four RCT comparing sirolimus DES vs. BMS Five RCT comparing paclitaxel DES vs. BMS Databases provided by manufacturers Unrestricted Patient-level analyses Follow-up: four years Acute, subacute, late stent thrombosis End Points Stent thrombosis Revascularization of target lesion STEMI and NSTEMI Mortality: overall, cardiac, and non cardiac Composite Overall mortality or AMI (STEMI and NSTEMI) Overall mortality or STEMI Cardiac mortality or STEMI Summary Stent thrombosis higher in DES Small increase in absolute risk (0.35 to 0.6%) After 12 months Less target revascularization with DES Mortality and risk of STEMI/NSTEMI comparable “Long-Term Outcomes with Drug-Eluting Stents versus Bare-Metal Stents in Sweden” NEJM 2007; 356:1009-1019. Methods Registry from Sweden (SCAAR) January 01, 2003 to December 31, 2004 All patients receiving stents Complete follow-up data available Twenty six centers Independent of commercial funding Longitudinal data (up to 12/31/2005) Hospitalizations for AMI and vital status Analyses Landmark Analysis 6 months Propensity Scores Patient characteristics Multivariable model Outcomes Primary Composite of death or myocardial infarction Secondary: Death Myocardial infarction Revascularization Restenosis Results Total of 19,771 patients 37,750 stents 24,215 procedures Breakdown: 6,033 received DES 13,738 received BMS Regional variation in DES utilization 0.6% to 41% Summary Effectiveness data set Unique patient population Mortality increased in DES group One year after deployment Persisted in follow-up “Outcomes and Complications Associated With Off-Label and Untested Use of Drug-Eluting Stents” JAMA 2007;297:1991-2000 Methods Prospective Multicenter Registry 140 medical centers (community and academic) PCI between 1/01/2005 to 6/31/2005 Clinical outcomes assessed at hospitalization, 30 days, 6 months, and 12 months Follow-up data Death, AMI, revascularization (PCI and CABG), and stent thrombosis Definitions Standard Discrete de novo lesions (< 30 mm) in native vessels of 2.5 to 3.5 cm in diameter Off-label Restenotic lesion, length > 30 mm, vessel diameter < 2.5 cm or > 3.5 cm, bypass graft Untested Left main, ostial, bifurcation, or totally occluded lesions Definitions Standard clopidogrel Three months after sirolimus DES Six months after paclitaxel DES Prolonged clopidogrel Beyond above Outcomes Effectiveness Target vessel repeat revascularization Safety Composite of death, AMI, or stent thrombosis In-hospital 30 day follow-up One year follow-up Summary Greater risk of complications with off-label use of DES Greater use of complications with untested use of DES “Clopidogrel Use and Long Term Clinical Outcomes After DES Implantation” JAMA 2007;297:159-168 Methods University base database BMS from 01/01/2000 to 07/31/2005 DES from 4/01/2003 t0 7/31/2005 Baseline demographics, LHC data, medical history, and physical examination Follow-up at 6 months, 12 months, and yearly thereafter (98% complete) Death and non fatal MI Use of aspirin and clopidogrel Methods Landmark Analyses Form of survival analysis Intermediate “event” is utilized Time: 6 months and 12 months after index PCI Four groups DES with clopidogrel DES without clopidogrel BMS with clopidogrel BMS without clopidogrel Methods Follow-up of 24 months Propensity scores for matching Demographics, CAD risk factors, h/o CHF/AMI, LHC findings, comorbidity index Cox proportional hazards Six Month Landmark Analysis Twelve Month Landmark Analysis Twelve Month Landmark Analysis Six Month Landmark Analysis Summary Prolonged therapy with dual anti-platelet therapy indicated for DES Length of duration unknown Comparable or better outcomes to BMS if combining DES with long term clopidogrel Cases Case #1 Aggressive management of CAD risk factors including an exercise program might be a reasonable choice. Case #2: While more data is being collected, use of clopidogrel might need to be prolonged indefinitely in patients with DES. What is the right question? Should we ever deploy a stent? Yes in high risk ACS (BMS Vs. DES) or after STEMI with residual ischemia Maybe in stable CAD Suitable vessel Suitable lesion In a patient with a DES, how should we manage it? Prolonged dual anti-platelet therapy “Other” Implications Regulatory role of FDA When should pharmacologic agents and/or devices be approved for use? Technology Assessment Should adoption of technology be regulated? By whom?