Endoscopy & ACS. 8/1/2014 Dr. Whang

Transcription

1 Endoscopy & ACS 8/1/2014 Dr. Whang

2 Outline I. Antiplatelets II. Coronary Artery Disease in U.S. III. GI Bleeding in ACS IV. ACC/AHA guidelines: Dual Antiplatelet Therapy in CAD V. PPI and Plavix Controversy

3 I. ANTIPLATELETS ASA Irreversibly acetylates COX-1 Thienopyridines Clopidogrel/Ticlodipine/Pra sugrel Irreversibly blocks P2Y 12 (ADP receptor on the surface of the platelet) Cangrelor/Ticagrelor Reversibly blocks P2Y 12 GP IIb/IIIa Inhibitors Abciximab/Eptifibatide/Tiro fiban Blocks fibrinogen & vwf from binding to activated GP IIb/IIIa

4 II. CAD in United States 2014 Heat and Stroke Statistics, AHA ~15.4 million with CHD (coronary heart disease) o Myocardial infarction 7.6M o Other: Angina pectoris (7.8M), Heart failure (5.1M), Stroke (6.8M), Congenital cardiovascular defects (650K 1.3M) Year 2010 ~492,000 patients underwent PCI (percutaneous coronary intervention) o 67% M, 33% F o 51% >= 65 y.o. o Stents: 75% DES vs. 25% BMS

5 Trends in inpatient cardiovascular procedures U.S.

6 III. GI Bleeding in ACS Bleeding Complications 1 Vascular access site (most common) usually after PCI retroperitoneal bleed 2 Intracerebral hemorrhage 3 GI Bleed Incidence UGIB = % If there is significant bleeding hypovolemia, hypoperfusion, decreased O2 delivery to the heart Inflammation, PLT activation may recurrent ischemia When there is bleeding. Decide if anti-thrombotic therapy needs to be held Concern recurrent ischemia, cardiac stent thrombosis, mortality

7 Contraindications for Fibrinolytic Therapy in STEMI ACCF/AHA STEMI Guideline-

8 ACCF/AHA STEMI Guideline

9 - Literature -

10 Gastrointestinal Bleeding in Patients with Acute Coronary Syndromes: Incidence, Predictors, and Clinical Implications Analysis from the ACUITY Trial (Acute Catheterization and Urgent Intervention Triage Strategy) JACC, 2009 Purpose: using ACUITY database, evaluate GIB within 30 days ACUITY Trial (8/ /2005) multicenter & randomized study, 17 countries, 450 centers, open label 13,819 patients with non ST-elevation ACS (mod-high risk) randomized to 3 antithrombin treatment strategies 1Heparin + GPIIb/IIIa inhibitor 2Bivalirudin + GPIIb/IIIa inhibitor 3Bivalirudin monotherapy Mandatory angiography within 72 hours triaged PCI / CABG / medical mgmt Daily ASA Clopidogrel load 300mg (within 2 hours of PCI), 75mg x 1 year in all CAD

11 Definition GIB: PHYSICIAN DOCUMENTED coffee ground emesis, hematemesis, melena, RBPR (within days after randomization) GIB = 178/13,819 (1.3%) triaged: 1.8% CABG > 1.4% PCI > 1% med mgmt 1.5% Heparin + GPI > 1.4% bivalirudin + GPI > 0.9% bivalirudin (p = 0.019) Higher TIMI risk scores High risk groups: 1. Elderly: 3.54% >80 yo % if <=50 2. Female 3. ST-segment elevation >=1mm 4. DM 5. Renal dysfunction (creatinine clearance < 60 ml/min) 6. Anemia, baseline (HCT <39% M; <36% F) 7. Smoking 9.6% died within 35 days 77% from cardiac etiology 6 patients with likely/definite stent thrombosis: 5 deaths

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13 Study Limitations: Data NOT collected: use of drugs which can increase GIB risk (warfarin, NSAIDs, steroids, SSRI s, spironolactone) use of PPI GIB after 30 days when medications were discontinued (ASA, thienopyridines)

14 Incidence, predictors and outcome of upper gastrointestinal bleeding in patients with acute coronary syndromes International Journal of Cardiology, 2010 Purpose: determine risk factors and outcomes for UGI bleed in ACS Study: case control study at tertiary care hospital in Israel 10/ / evaluated 7240 patients: admitted to coronary care unit with ACS discharge diagnosis STEMI/NSTEMI, UA Identified those with UGI bleed while hospitalized Excluded those who had an UGI bleed within 30 days prior to admission Define UGIB: coffee ground emesis, hematemesis, melena UGIB: 64/7,240 (*0.9%) Endoscopy available 35/64 (endoscopy per MD discretion) Strongest independent predictor in-hospital mortality (compared to intra-aortic balloon counterpulsation, LV dysfunction) Strong predictor of 1-year mortality

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17 Anti-platelet therapy Discontinued 2/2 UGIB (while hospitalized) UGIB 64/7,240 (0.9%) # patients with stent thrombosis 5 of 64 (1 fatal) 17 (12%) 2 Monotherapy at discharge 26 (36%) 2 Dual therapy at discharge 24 (37%) 1 Limitations: Retrospective study Endoscopy not required for all GI bleeds

18 CV disease STEMI NSTEMI, UA BMS IV. ACC/AHA Guidelines Dual Anti-Platelet Therapy Duration Clopidogrel + ASA Minimum 14 days *despite fibrinolytic therapy OR PCI 1 month (up to 1 year) *if conservative management 1 month (up to 1 year) Class, Evidence IB IA 1A [1B] 1B 2 weeks Clopidogrel (if increased risk bleed) DES 1 year (NOT increased risk bleed) 1B CAD, chronic stable NOT RECOMMENDED except: 1. ACS <12 months 2. PCI with DES

19 - Concerns Early discontinuation of DAT (dual anti-platelet therapy) o Risk stent thrombosis DAT vs. Single Antiplatelet Therapy o 3-fold increased risk of UGIB

20 - Things to Consider - 1. Do I need to HOLD anti-platelet therapy for endoscopic evaluation? 2. If yes, what is the OPTIMAL TIME/LENGTH OF TIME to hold anti-platelet therapy?

21 ASGE 2009 Guidelines

22 Elective Endoscopic Procedures After ACS or Stent Defer (if possible) until complete minimal duration of antithrombotic therapy After minimal duration antithrombotic therapy o Hold clopidogrel or ticlodipine x 7-10days, continue ASA o Consider adding ASA during periendoscopic period to decrease risk

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25 V. PPI & Plavix Controversy Metabolized in the liver by a common pathway --- cytochrome P450 isoenzymes (CYP2C19) Concern PPI decreases Plavix s inhibitory effect on PLT P2Y12 R --- thus decreasing the inhibitory effect on platelet aggregation Increased prothrombotic state (i.e. less platelet inhibition) - Literature -

26 Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Proton Pump Inhibitors Following Acute Coronary Syndrome JAMA, 2009 Purpose: Patients hospitalized for ACS and subsequently discharged --- evaluate outcomes clopidogrel +/- PPI Study: Retrospective cohort study VHA medical centers /2003 1/2006 Patients: 8,205 patients hospitalized 2/2 ACS & filled clopidogrel prescription after discharge Excluded: Prior h/o GI bleed (n=414), GIB during first hospitalization OR after discharge (n=1288), Filled prescription for H2-antagonist (n=1547) Primary Outcome: all-cause mortality or rehospitalization for ACS (after initial discharge for ACS) Secondary Outcome: rehospitalization for ACS, revascularization/pci/cabg, all-cause mortality after initial discharge for ACS M.C. PPI s used: omeprazole & rabeprazole

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28 PPI s Prescribed 1. Omeprazole* 3,132 (59.7%) 2. Rabeprazole* 151 (2.9%) 3. Lansoprazole 22 (0.4%) 4. Pantoprazole 15 (0.2%) 5. >1 PPI 1,924 (36.7%) *mean daily dose = 10.7 mg (SD = 26.5) // median daily dose = 20 mg (interquartile range mg) **did not find PPI dose-response & adverse outcome 8,205 patients Clopidrogel without PPI --- 2,961 (36.1%) Clopidogrel + PPI --- 5,244 (63.9%)

29 1,080 days: Cumulative incidence rates: deaths OR rehospitalization 2/2 ACS

30 Study limitations: 1. May be missing data --- can buy OTC omeprazole since 6/2003; VA patients may have followed-up at non-va facilities 2. Possible unmeasured confounder (?sicker patients on PPI) Do NOT recommend routine prophylactic prescription PPI for ACS

31 References: 1. Heart Disease and Stroke Statistics 2014 Update: A Report From the American Heart Association. Circulation. 2014; 129:e28-e ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction. JACC. 3. Management of Platelet-Directed Pharmacotherapy in Patients With Atherosclerotic Coronary Artery Disease Undergoing Elective Endoscopic Gastrointestinal Procedures. Becker R, Scheiman J, Dauerman H, Spencer F, Rao S, Sabatine M, Johnson D, Chan F, Abraham N, Quigley E. ACJ/JACC White Paper. Am J Gastroenterol 2009; 104: Gastrointestinal Bleeding in Patients with Acute Coronary Syndromes: Incidence, Predictors, and Clinical Implications Analysis from the ACUITY Trial (Acute Catheterization and Urgent Intervention Triage Strategy). JACC, Incidence, predictors and outcome of upper gastrointestinal bleeding in patients with acute coronary syndromes. International Journal of Cardiology, Risk of Adverse Outcomes Associated With Concomitant Use of Clopidogrel and Propton Pump Inhibitors Following Acute Coronary Syndrome. JAMA Images: 2. d=