Presentation on theme: "STRIVE TM. STRIVE TM Learning Objectives Apply the current ACC/AHA guidelines for management of STEMI and UA/NSTEMI patients to the development of critical."— Presentation transcript:
STRIVE TM Learning Objectives Apply the current ACC/AHA guidelines for management of STEMI and UA/NSTEMI patients to the development of critical pathways for ACS Develop or modify tools for effectively implementing critical pathways for ACS in the hospital Interpret the findings of recent clinical trials in ACS and assess their applicability to the development of up-to-date critical pathways for ACS After taking part in this activity, participants should be able to:
STRIVE TM Learning Objectives (cont.) Outline the results from national quality improvement initiatives showing that critical pathways work to enhance patient outcomes Work with hospital critical pathways teams to overcome barriers to developing, improving, and implementing critical pathways for ACS After taking part in this activity, participants should be able to:
STRIVE TM Pathophysiology and Epidemiology of Acute Coronary Syndromes
STRIVE TM Atherosclerosis Atherothrombosis: A Progressive Phenomenon Ischemic stroke/TIA MI Acute limb ischemia Cardiovascular death Unstable angina Adapted from Libby P. Circulation. 2001;104: ACSACS Thrombosis Libby P. Sci Am. 2002;286:46-55.
STRIVE TM No ST elevationST elevation Unstable angina NSTEMISTEMI Spectrum of CAD/ACS Stable angina Source (Photos): Davies MJ. Heart. 2000;83: CAD = coronary artery disease; NSTEMI = non-ST-segment elevation myocardial infarction; STEMI = ST-segment elevation myocardial infarction.
STRIVE TM UA/NSTEMI ~ 1.23 Million Discharges Per Year ~0.33 Million Discharges Per Year STEMI Epidemiology of CAD/ACS CAD = coronary artery disease; ACS = acute coronary syndrome; UA = unstable angina; MI = myocardial infarction; NSTEMI = non–ST-segment elevation MI; STEMI = ST-segment elevation MI. American Heart Association. Heart Disease and Stroke Statistics—2006 Update. Circulation. 2006; e85-e151. Estimates for STEMI and NSTEMI proportions of MI extrapolated from statistics in Wiviott S, et al. J Am Coll Cardiol. 2006;47; Million Hospital Discharges for ACS
STRIVE TM Angiographic and angioscopic images of a 58-year-old man with anterior myocardial infarction Multiple “vulnerable” plaques detected in nonculprit segments 9-12 Culprit lesion with thrombus (red) detected in #8 Multiple “vulnerable” plaques detected in nonculprit segments 1-7 Evidence of Multiple “Vulnerable” Plaques in ACS Reprinted with permission from Asakura M, et al. J Am Coll Cardiol. 2001;37:
STRIVE TM Overlap of Atherosclerotic Disease Coronary Artery Disease Cerebrovascular Disease Peripheral Arterial Disease Patients with 1 manifestation often have coexistent disease in other vascular beds Ness J, Aronow WS. J Am Geriatr Soc. 1999;47: % overlap in 2 vascular beds
STRIVE TM The REACH Registry The REACH (REduction of Atherothrombosis for Continued Health) Registry has recruited outpatients who have had, or are at high risk of having, symptoms of atherothrombosis The Registry aims to study a contemporary stable patient population from various regions of the world in order to: –Describe the characteristics and management of these patients and of each subgroup –Assess the long-term risk of atherothrombotic events in the global population and in each subgroup –Assess the amount of “cross-risk” across subgroups –Compare outcomes within different subject profiles –Define predictors of risk for subsequent atherothrombotic events Follow-up planned at 12 and 21 months, extended to 3 and 4 years Steg PG. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga.
STRIVE TM Bhatt DL, et al; for the REACH Registry Investigators. JAMA. 2006;295: Baseline Prevalence of Polyvascular Disease in the REACH Registry Single Arterial Bed% Overall65.9 CAD Alone44.6 CVD Alone16.6 PAD Alone4.7 Polyvascular Disease Overall15.9 CAD + CVD8.4 CAD + PAD4.7 CVD + PAD1.2 CAD + CVD + PAD1.6 Multiple Risk Factors18.3
STRIVE TM REACH 1-Year Results: Single vs Multiple and Overlapping Atherothrombotic Locations: The Example of CAD Rates adjusted for age and risk factors. *TIA, unstable angina, other ischemic arterial event including worsening of PAD. Steg PG. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 12, 2006; Atlanta, Ga. % CV DeathNonfatal MINonfatal Stroke Death/MI/ Stroke Death/MI/ Stroke/Hosp* CAD alone CAD+CVD CAD+PAD CAD+CVD+PAD
STRIVE TM ST-Segment Elevation Myocardial Infarction (STEMI) in the Emergency Department
STRIVE TM Antman EM, et al. J Am Coll Cardiol. 2004;44: STEMI: Prehospital Issues EMS –Early defibrillation –Use of automated external defibrillators (AEDs) –9-1-1 dispatcher training –National protocols Chest pain evaluation and treatment –Chewable ASA unless contraindicated –Prehospital ECG –Reperfusion checklist Prehospital fibrinolysis –Upgraded to Class IIa (Level B) recommendation
STRIVE TM EMS Transport Onset of symptoms of STEMI EMS dispatch EMS on-scene Encourage 12-lead ECGs Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min GOALS PCI capable Not PCI capable Hospital fibrinolysis: door-to-needle within 30 min EMS triage plan Inter- hospital transfer Golden hr = 1st 60 minTotal ischemic time: within 120 min Patient EMS Prehospital fibrinolysis EMS-to-needle within 30 min EMS transport EMS-to-balloon within 90 min Patient self-transport Hospital door-to-balloon within 90 min Dispatch 1 min 5 min 8 min Options for Transport of Patients With STEMI and Initial Reperfusion Treatment Adapted with permission from Antman EM, et al. Available at: Accessed September 1, 2006
STRIVE TM Ambulance arrival ED arrivalInhospital lytic Control Prehosp 63 min (48–89) 31 min (24–37) 32 min saved Data=Median Times (Q1-Q3) P<.0001* First r-PA bolus ER-TIMI 19: Time Saved to First r-PA Bolus with Prehospital Administration *Adjusted for any effect of site and interaction. Adapted with permission from Morrow DA, et al. J Am Coll Cardiol. 2002;40:71-77.
STRIVE TM STEMI: Brief Physical Exam in ED Airway, breathing, circulation (ABC) Vital signs, general observation Presence or absence of –Jugular venous distention –Stroke –Pulses –Systemic hypoperfusion (cool, clammy, pale/ashen) Pulmonary auscultation for rales Cardiac auscultation for murmurs or gallops Antman EM, et al. Available at: Accessed September 1, 2006.
STRIVE TM ACC/AHA 2004 STEMI Guidelines: Acute Medical Therapy General treatment measures Antman EM, et al. Available at: Accessed September 1, Analgesics Nitrates Oxygen β-blockers (Note: not for acute use in patients with evidence of heart failure) Primary PCI or coronary thrombolysis (primary PCI preferred after 3 hr) ASA (162–325 mg, acute dose) Heparin If PCI – Clopidogrel – GP IIb/IIIa inhibitors Infarct size limitation Reperfusion Antithrombotic and antiplatelet therapy
STRIVE TM Primary PCI vs Thrombolysis in STEMI: Quantitative Analysis (23 RCTs, N=7739) Adapted with permission from Keeley EC, et al. Lancet. 2003;361: PCI Thrombolytic therapy Frequency (%) Short-term outcomes (4-6 wk) Death P= Nonfatal MI P< Recurrent Ischemia P< Hemor- rhagic Stroke P< Major Bleed P=.032 Death, Nonfatal Reinfarction, or Stroke P<.000 1
STRIVE TM PCI-related Time Delay (Door-to-Balloon minus Door-to-Needle) Circle sizes = sample size of individual study Solid line=weighted meta-regression For every 10-min delay to PCI: 1% reduction in mortality difference vs lytics. Nallamothu BK, Bates ER. Am J Cardiol. 2003;92: Favors PCI Favors lysis P= min Absolute Risk Difference in Death (%) Mortality With 1° PCI vs Time Delay
STRIVE TM Clinical Trials of Interhospital Transfer for PCI vs Fibrinolysis Mortality (%) (N=200)(N=137)(N=850)(N=1129) (N=150) LIMI 1 PRAGUE-1 2 AIR-PAMI 3 PRAGUE-2 4 DANAMI 5 On-site fibrinolysisTransfer for PCI 1. Vermeer F, et al. Heart. 1999;82: Widimsky P, et al. Eur Heart J. 2000;21: Grines CL, et al. J Am Coll Cardiol. 2002;39: Widimsky P, et al. Eur Heart J. 2003;24: Andersen HR, et al. N Engl J Med. 2003;349:
STRIVE TM Nallamothu BK, et al. Circulation. 2005;111: STEMI: Transfer for PCI NRMI ( ) 4278 Patients 28.4>4 h 55.42–4 h 16.2<2 h 4.2<90 min % of PatientsDoor-to-Balloon Time
STRIVE TM Facilitated PCI, Rescue PCI, and Adjunctive Therapy for STEMI
STRIVE TM Facilitated PCI and Rescue PCI: Definition of Terms Facilitated PCI –Fibrinolytics or other pharmacologic agents to “facilitate” immediate percutaneous coronary intervention Rescue PCI –Percutaneous coronary intervention for failed fibrinolysis Dauerman HL, Sobel BE. J Am Coll Cardiol. 2003;42: Antman EM, et al. Available at:
STRIVE TM Rescue Angioplasty Versus Conservative Treatment or Repeat Thrombolysis (REACT) Trial Primary End Point Composite of death, reinfarction, stroke, or severe heart failure within 6 months Conservative Treatment Including IV UFH for 24 h (n=141) Rescue PCI Angiography with or without revascularization (n=144) Repeated thrombolysis with alteplase or reteplase (n=142) Gershlick AH, et al. N Engl J Med. 2005;353: STEMI patients with failed thrombolysis ASA and thrombolytic therapy (60% rec’d streptokinase) within 6 h of chest pain onset, <50% ST-segment resolution within 90 minutes
STRIVE TM RESCUE PCI: REACT Trial — Primary End Point Primary End Point = death, recurrent MI, severe heart failure, or cerebrovascular event within 6 months REACT = Rescue Angioplasty versus Conservative Treatment or Repeat Thrombolysis. Adapted with permission from Gershlick AH, et al. N Engl J Med. 2005; 353: Days After Randomization Probability of Event-free Survival Rescue PCI 84.6% 95% Cl, Conservative therapy 70.1% 95% Cl, Repeated thrombolysis % Cl, P=.004
STRIVE TM STEMI < 6 h Lytic eligible Lytic choice by MD (TNK, tPA, rPA, SK) Double-blind, double-dummy ASA Day 30 1° Efficacy End Point: Death or Nonfatal MI 1° Safety End Point: TIMI Major Hemorrhage ExTRACT-TIMI 25: Protocol Design UFH (N = 10,223) 60 U / kg bolus (4000 U) Inf 12 U / kg / h (1000 U / h) Duration: at least 48 h Cont’d at MD discretion ExTRACT = Enoxaparin and Thrombolysis Reperfusion for Acute Myocardial Infarction Antman EM et al. N Engl J Med. 2006;354: Adapted with permission from ENOXAPARIN (N=10,256) < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) ≥ 75 y: No bolus SC 0.75 mg / kg q 12 h (Hosp DC) CrCl < 30: 1.0 mg / kg q 24 h ENOXAPARIN (N=10,256) < 75 y: 30 mg IV bolus SC 1.0 mg / kg q 12 h (Hosp DC) ≥ 75 y: No bolus SC 0.75 mg / kg q 12 h (Hosp DC) CrCl < 30: 1.0 mg / kg q 24 h
STRIVE TM Main Results From ExTRACT-TIMI 25 Primary End point: Death or nonfatal re-MI by 30 days Main Secondary Endpoint: Death, non-fatal re-MI, urgent revascularization by 30 days UFH ENOX Days % % RR = 0.83 p = RR = 0.81 p = Adapted with permission from Adapted with permission from Antman EM, et al. N Engl J Med. 2006;354: Major bleeding: 1.4% with UFH vs 2.1% with enoxaparin (P<.001) ICH:.7% for UFH vs.8% for enoxaparin (P=.14)
STRIVE TM ExTRACT-TIMI 25: Net Clinical Benefit at 30 Days Death or Nonfatal MI or Nonfatal ICH Death or Nonfatal MI or Nonfatal Major Bleed Death or Nonfatal MI or Nonfatal Disabling Stroke Enoxaparin BetterUFH BetterRR UFH (%)Enox (%)RRR (%) Prespecified Definitions P<.001 Adapted with permission from Antman EM, et al. N Engl J Med. 2006;354:
STRIVE TM ExTRACT-TIMI 25 PCI Cohort: Primary End point Death or Nonfatal MI by 30 days ENOX 10.7% Days Death or MI (%) UFH 13.8% RR 0.77 P=0.001 Gibson M. Presented at World Congress of Cardiology; September 4, 2006; Barcelona, Spain. Adapted with permission from
STRIVE TM ExTRACT-TIMI 25 PCI Cohort: Safety EventENOXUFHRRP-Value n=2,238 n=2,377 TIMI Major Bleed1.4%1.6%0.87 ( ).56 TIMI Minor Bleed3.3%2.4%1.34 ( ).09 TIMI Major or 4.6%4.0%1.15 ( ).31 Minor Bleed ICH 0.2%0.4%0.42 ( ).18 Stroke0.3%0.9%0.30 ( ).006 Gibson M. Presented at World Congress of Cardiology; September 4, 2006; Barcelona, Spain. Adapted with permission from
STRIVE TM OASIS-6 Trial: Study Design 12,092 patients presenting with STEMI within 24 hours of symptom onset (shortened to 12 hours of symptom onset midway through trial) Randomized, Blinded, Factorial 28% female; mean age, 62 years; mean follow-up, 3-6 months Fondaparinux n=2, mg/day for up to 8 days or hospital discharge Placebo n=2,835 Fondaparinux n=3, mg/day for up to 8 days or hospital discharge UFH n=3,221 Primary end point: Composite of death or reinfarction at 30 days Secondary end point: Composite of death or reinfarction at 9 days and at final follow-up Stratum 1 (No UFH) n=5,658 Stratum 2 (UFH) n=6,434 Yusuf S, et al. JAMA. 2006;295: Adapted with permission from
STRIVE TM OASIS-6 Trial: Results 15% Primary End Point: Death/Reinfarction (%) P=.008 P=.003P=.008 Frequency 12% 9% 6% 3% 0% days9 days3-6 months Fondaparinux (n=6036 ) Control (n=6056) 14% Reduction in Death/MI at 30 days: Stratum 1 (No UFH indicated) P<.05 Reduction in Death/MI: Stratum 2 (UFH Indicated) P=NS p= % 10% 8% 6% 4% 2% 0% FondaparinuxPlacebo 14% 12% 10% 8% 6% 4% 2% 0% FondaparinuxUFH Yusuf S, et al. JAMA. 2006;295: Adapted with permission from
STRIVE TM CLARITY–TIMI 28: Study Design Fibrinolytic, ASA, Heparin Clopidogrel 300 mg + 75 mg qd Coronary Angiogram (2-8 days) Primary end point: Occluded artery (TIMI flow grade 0/1) or death/MI by time of angio Randomized Placebo Double-blind, randomized, placebo-controlled trial in 3491 patients, aged yrs, with STEMI <12 hours Study Drug 30-day clinical follow-up Open-label clopidogrel per MD in both groups CLARITY-TIMI 28 = CLopidogrel as Adjunctive ReperfusIon TherapY – Thrombolysis In Myocardial Infarction. Sabatine MS, et al. N Engl J Med. 2005;352:
STRIVE TM CLARITY–TIMI 28: End Points PlaceboClopidogrel n=1752n= % Odds Reduction Occluded Artery or Death/MI (%) Sabatine MS, et al. N Engl J Med. 2005;352: Days Endpoint (%) Placebo Clopidogrel Odds Ratio: 0.80 (95% CI, ) P=.03 20% CV Death, MI, RI Urg Revasc Primary End Point Occluded Artery (or Death/MI Through Angio/HD)
STRIVE TM Treatment:Clopidogrel 75 mg daily vs placebo (aspirin 162 mg daily in both groups) Inclusion:Suspected acute MI (ST change or LBBB) within 24 h of symptom onset Exclusion:Primary PCI or high risk of bleeding 1 Outcomes:Death and death, re-MI, or stroke up to 4 weeks in hospital (or prior discharge) COMMIT/CCS-2: Study Design Mean treatment and follow-up: 16 days COMMIT = ClOpidogrel & Metoprolol in Myocardial Infarction Trial. COMMIT Collaborative Group. Lancet. 2005;366:
STRIVE TM COMMIT: Effect of Clopidogrel on Death, Re-MI, or Stroke 9% (SE3) relative risk reduction (2P=.002) Placebo + ASA: 2311 events (10.1%) Clopidogrel + ASA: 2125 events (9.3%) Days Since Randomization (up to 28 days) Event (%) COMMIT Collaborative Group. Lancet. 2005;366: Mortality (%) Days Since Randomization (up to 28 days) Placebo + ASA: 1846 deaths (8.1%) Clopidogrel + ASA: 1728 deaths (7.5%) 7% (SE3) relative risk reduction (2P=.03) COMMIT = ClOpidogrel & Metoprolol in Myocardial Infarction Trial.
STRIVE TM 2004 ACC/AHA STEMI Guidelines Secondary Prevention Goals Preventive MeasureGoal Smoking →Complete cessation BP control →<140/90 mm Hg or <130/80 mm Hg if chronic kidney disease or diabetes Physical activity →Minimum: 30 min 3-4 days per week; optimal: daily Lipid management (TG <200 mg/dL) → Primary goal: LDL-C <<100 mg/dL Lipid management (TG >200 mg/dL) → Primary goal: Non–HDL-C <<130 mg/dL Weight management →Goal: BMI 18.5 to 24.9 kg/m 2 Diabetes management →Goal: HbA 1c <7% Antman EM, et al. J Am Coll Cardiol. 2004;44:E1-E211. Available at:
STRIVE TM Managing STEMI in 2006: Summary Acute therapy focuses on reperfusion and antithrombotic therapy PCI generally preferred over fibrinolysis when a skilled PCI lab is available with surgical backup and door-to-balloon time is <90 min Fibrinolysis generally preferred when invasive strategy is not an option or when delay to PCI is anticipated (>90 min door-to-balloon) Current ACC/AHA STEMI guidelines recommend IV UFH as ancillary therapy to reperfusion therapy (Class I) ExTRACT-TIMI 25 showed enoxaparin superior to current standard of UFH as the antithrombin to support fibrinolysis Fondaparinux effective in STEMI without increasing risk of bleeding or stroke (OASIS-6), but some subsets did not benefit (patients heading for PCI; patients in whom UFH, not placebo, was the control) Clopidogrel on top of aspirin results in significant further improvements in the reperfusion of patients with STEMI (CLARITY/COMMIT)
STRIVE TM Unstable Angina/ Non–ST-Segment Elevation Myocardial Infarction (UA/NSTEMI) Risk Stratification and Medical Management
STRIVE TM ACC/AHA Class I Recommendations For Evaluation of Chest Pain Patients with suspected ACS with chest discomfort at rest for >20 min, hemodynamic instability, or recent syncope or presyncope should be strongly considered for immediate referral to an ED or to a specialized chest pain unit Assess likelihood of CAD Assess risk of adverse events Adapted from Braunwald E, et al. Available at:
STRIVE TM Likelihood of ACS Secondary to CAD “CONFIDENCE OF DIAGNOSIS” Adapted from Braunwald E, et al. Available at: HighIntermediateLow HistoryChest or left arm painChest or left armSx w/o intermediate Sx as in prior anginapain; age >70 yrlikelihood character- Known history of CADMale sex; DMistics; recent cocaine ExamTransient MR,ExtracardiacChest pain hypotension,vascularreproduced diaphoresis,diseaseby palpation pulmonary edema, or rales ECGNew transientFixed Q wavesT-wave flattening or ST-segment deviationAbnormal ST-seginversion in leads or T-wave inversionor T-waves notw/dominant R waves with symptomsdocumented as newNormal ECG CardiacElevatedNormalNormal Markers
STRIVE TM TIMI Risk Score for UA/NSTEMI: 7 Independent Predictors 1. Age ≥65 y 2. ≥3 CAD risk factors (high cholesterol, family history, hypertension, diabetes, smoking) 3. Prior coronary stenosis ≥50% 4. Aspirin in last 7 days 5. ≥2 anginal events ≤24 h 6. ST-segment deviation 7. Elevated cardiac markers (CK-MB or troponin) Antman EM, et al. JAMA. 2000;284: Number of Predictors /123456/7 % Death / MI / Revasc
STRIVE TM Troponin I, C-Reactive Protein, and B-type Natriuretic Peptide as Determinants of 30-Day Mortality in Acute Coronary Ischemia: A Multimarker Approach Adapted with permission from Sabatine MS, et al. Circulation. 2002;105: P=.014 P< Day Mortality Relative Risk OPUS-TIMI TACTICS-TIMI Elevated Cardiac Biomarkers (N) n=67n=150 n=155 n=78 n=504 n=717 n=324 n=90
STRIVE TM Future of Biomarkers in ACS: Toward a Multimarker Strategy hs-CRP = high-sensitivity C-reactive protein; CD40L = CD 40 ligand; BNP = brain natriuretic peptide; NT = N-terminal; HbA 1c = hemoglobin A 1c ; CrCl = creatinine clearance. Adapted with permission from Morrow DA, Braunwald E. Circulation. 2003;108: Myocyte Necrosis Inflammation Troponin Accelerated Atherosclerosis Vascular Damage Hemodynamic Stress hs-CRP, CD40L HbA 1c Blood glucose CrCl Microalbuminuria Biomarker Profile in ACS BNP, NT-proBNP
STRIVE TM Conservative Strategy Invasive Strategy With GP IIb/IIIa Inhibitor TRS = TIMI Risk Score. Adapted with permission from Cannon CP. Circulation. 2002;106: Higher Risk +Troponin, ST s, TRS 3, Recurrent Ischemia, CHF, Prior Revascularization Lower Risk – ECG, – Markers, TRS 0-2 Aspirin, Clopidogrel, Heparin/LMWH (IIa Enox) β-blocker, Nitrates Evidence-Based Risk Stratification to Target Therapies in UA/NSTEMI Long-term Medical Therapy (Aspirin, Clopidogrel, Statin, β-blocker, ACEI)
STRIVE TM ACC/AHA Guidelines for UA/NSTEMI Bed rest with continuous ECG monitoring Nitroglycerin started sublingual, then IV Supplemental O 2 for cyanosis or respiratory distress; confirm SaO 2 >90% Morphine sulfate IV for pain, anxiety, CHF β-blocker started IV, then PO; calcium antagonist if β-blocker and/or nitrates contraindicated or insufficient Add ACE inhibitor if hypertension persists Adapted from Braunwald E, et al. Available at: Anti-ischemic Therapy
STRIVE TM Definite ACS With Cath and PCI or Higher Risk (IIa) Lower-Risk ACS Possible ACS Aspirin + IV heparin/LMWH* + IV platelet GP IIb/IIIa inhibitor clopidogrel Aspirin + SQ LMWH* or IV heparin clopidogrel Aspirin ACC/AHA Guidelines for UA/NSTEMI Antithrombotic Therapy Class I Recommendations* *Class IIa: enoxaparin preferred over IV heparin. Adapted from Braunwald E, et al. Available at:
STRIVE TM * Placebo 158 ASA Patients (%) * Placebo 118 ASA * Placebo 279 ASA Lewis HD Jr, et al. N Engl J Med. 1983;309: Theroux P, et al. N Engl J Med. 1988;319: Cairns JA, et al. N Engl J Med. 1985;313: * Placebo 397 ASA The RISC Group. Lancet. 1990;336: Death or MI *P=.0005*P=.012*P=.008*P<.0001 ASA in UA/NSTEMI
STRIVE TM Adapted with permission from Yusuf S, et al. Circulation. 2003;107: Proportion Event-Free RRR: 18% 95% CI, 0.70–0.95 P=.009 Clopidogrel Placebo CV Death, MI, or Stroke >30 Days–1 Year Proportion Event-Free Month Week RRR: 21% 95% CI, 0.67–0.92 P=.003 Clopidogrel Placebo CV Death, MI, or Stroke First 30 Days No. at Risk Clopidogrel Placebo No. at Risk CURE Study: Event-Free Survival RRR = relative risk reduction.
STRIVE TM Adapted with permission from Yusuf S, et al. Circulation. 2003;107: CURE: Efficacy of Very Early Clopidogrel Therapy in ACS Patients Hours After Randomization P=.003 Placebo + Aspirin (n=6303) Clopidogrel + Aspirin (n=6259) 34% Relative Risk Reduction CV Death, MI, Stroke, Severe Ischemia Within First 24 Hours Cumulative Hazard Rate
STRIVE TM *Other standard therapies were used as appropriate. Peters RJ, et al. Circulation. 2003;108: Clopidogrel + Aspirin* Placebo + Aspirin* Aspirin Dose mg 1.9%3.0% mg2.8%3.4% mg3.7%4.9% CURE: Major Bleeding by Aspirin Dose Through Follow-up
STRIVE TM Prior CABG High-risk findings on noninvasive stress testing PCI within 6 months Recurrent angina/ischemia with CHF, S 3, PE, rales, etc. Sustained VTST-segment depression Hemodynamic instabilityElevated TnT or Tnl Ejection fraction <.40Recurrent angina/ischemia Class I An early invasive strategy in patients with UA/NSTEMI and any of the following high-risk indicators (Level of Evidence: A) Braunwald E, et al. J Am Coll Cardiol. 2002;40: ACC/AHA Guidelines for UA/NSTEMI: Early Invasive Strategy
STRIVE TM Favors Invasive Favors Conservative Odds Ratio Death or MI OR 0.82, P<.001 Trial (N) TIMI IIIB (1473) VANQWISH (920) MATE (201) FRISC II (2457) TACTICS (2220) RITA 3 (1810) Total (N=9212) Invasive Management of UA/NSTEMI Meta-analysis: Death/MI at End of Follow-up (mean 17.3 months) VINO (131) Inv (%)Cons (%) Adapted with permission from Mehta S, et al. JAMA. 2005;293:
STRIVE TM Patients (N): Adapted with permission from Cannon CP, Turpie AG. Circulation. 2003;107: Optimal Strategy for UA/NSTEMI Conservative Invasive TIMI IIIB MATE VANQWISH FRISC II TACTICS- TIMI 18 VINO RITA-3 TRUCS ISAR-COOL ICTUS
STRIVE TM Benefit of Clopidogrel in PCI-CURE According to Timing of PCI Lewis BS, et al. Am Heart J. 2005;150: Cumulative Hazard Rates Days of Follow-up <48 hrs after rand RR:.53 ( ) Denotes median Time to PCI Cumulative Hazard Rates Days of Follow-up PCI ≥ 48 hrs from rand and during initial hosp RR:.72 ( ) Clopidogrel Placebo Cumulative Hazard Rates PCI after hospital discharge Days of Follow-up RR:.70 ( )
STRIVE TM Clopidogrel No TrialPretreatmentPretreatment PCI-CURE CREDOn/an/a PCI-CLARITY Overall Meta-analysis of Clopidogrel Pretreatment CV Death or MI after PCI (%) MI before PCI (%) OR (95% CI) OR: 0.67 P=.005 Favors Pretreatment Favors No Pretreatment OR: 0.71 P=.004 Adapted with permission from Sabatine MS, et al. JAMA. 2005;294: ClopidogrelNo TrialPretreatmentPretreatment PCI-CURE CREDO PCI-CLARITY Overall3.95.5
STRIVE TM ACC/AHA/SCAI 2005 Guideline Update for PCI Oral Antiplatelet Adjunctive Therapies A loading dose of clopidogrel should be administered before PCI is performed IIIaIIbIII A Adapted from Smith SC Jr, et al. Available at: An oral loading dose of 300 mg, administered at least 6 hours before the procedure, has the best established evidence of efficacy B
STRIVE TM ARMYDA-2 Trial: Design and Primary End Point Primary composite of death, MI, or target vessel revasc at 30 days P= % 2% 4% 6% 8% 10% 12% 14% High DoseStandard Dose 12 High Loading Dose of Clopidogrel 600 mg Pre-PCI Standard Loading Dose of Clopidogrel 300 mg Pre-PCI 255 patients with stable CAD or NSTEMI prior to PCI 13% received GP IIb/IIIa inhibitors 20% received drug-eluting stents Randomized 4-8 Hours Pre-PCI ARMYDA-2 = Antiplatelet Therapy for Reduction of Myocardial Damage During Angioplasty. Patti G, et al. Circulation. 2005;111:
STRIVE TM 30-Day Death or Nonfatal MI Risk Ratio and 95% CI Placebo Better GP IIb/IIIa Inhibitor Better Trial Pooled 11.5% Placebo GP IIb/IIIa Inhibitor 10.7% 29,855 n 0.92 (0.86, 0.995) P=.037 PRISM-PLUS11.9%10.2% 1,915 PURSUIT15.7%14.2% 9,461 PARAGON A11.7%11.3% 2, % PRISM 5.8% 3, PARAGON B11.4%10.5% 5,165 GUSTO-IV ACS 8.0%8.7% 7,800 GP IIb/IIIa Inhibition for Non–ST-Elevation ACS Boersma E, et al. Lancet. 2002;359: CI = confidence interval.
STRIVE TM GP IIb/IIIa Inhibitor During Medical Rx and After PCI: CAPTURE, PURSUIT, PRISM-PLUS 0% 2% 4% 6% 8% 10% PCI N=2754 P=.001 N=12,296 P= h+48 h+72 h+24 h+48 h 4.3% 2.9% 8.0% 4.9% Death or MI Medical Rx/Pre-PCI Post-PCI Control GP IIb/IIIa inhibitor 0 Adapted with permission from Boersma E, et al. Circulation. 1999;100:
STRIVE TM Benefits of GP IIb/IIIa by Troponin Status in Clinical Trials Newby KL, et al. Circulation. 2001;103: TnT-NegativeTnT-Positive PARAGON-B PRISM CAPTURE Combined GP IIb/IIIa Better GP IIb/IIIa Worse GP IIb/IIIa Better GP IIb/IIIa Worse
STRIVE TM ISAR-REACT 2: Cumulative Incidence of Death, MI, or Urgent TVR in Subsets With and Without Elevated Troponin levels (>0.03 µg/L) ISAR-REACT 2 = Intracoronary Stenting and Antithrombotic Regimen: Rapid Early Action for Coronary Treatment 2. Adapted with permission from Kastrati A, et al. JAMA. 2006;295: Days After Randomization Cumulative Rate of Primary End Point, % Placebo Group (n=1010) Abciximab Group (n=1012) Troponin >0.03 µg/L Log-Rank P=.02 Troponin <0.03 µg/L Log-Rank P=.98
STRIVE TM ACC/AHA UA/NSTEMI 2002 Guideline Update: Platelet GP IIb/IIIa Inhibitors Any GP IIb/IIIa inhibitor + ASA/heparin for all patients, if cath/PCI planned IIIaIIbIII *High-risk: age >75 y; prolonged, ongoing CP; hemodynamic instability; rest CP w/ ST ; VT; positive cardiac markers. A A B Eptifibatide or tirofiban + ASA/heparin for high-risk* patients in whom early cath/PCI is not planned Any GP IIb/IIIa inhibitor for patients already on ASA + heparin + clopidogrel, if cath/PCI is planned Adapted from Braunwald E, et al. Available at:
STRIVE TM Anticoagulation in UA/NSTEMI 4 classes of anticoagulants are available –Unfractionated heparin (UFH) –Low-molecular-weight heparins (LMWH) –Direct thrombin inhibitors –Factor Xa inhibitors Current guidelines support use of UFH and LMWH, with enoxaparin preferred over UFH (Class IIa) Recent studies suggest direct thrombin inhibitors (bivalirudin) and factor Xa inhibitors (fondaparinux) may be appropriate new options for anticoagulation –Effective, lower risk of bleeding
STRIVE TM Meta-analysis: Enoxaparin vs UFH in UA/NSTEMI Death or MI at 30 Days* TrialEnox (%)UFH (%)Odds ratio [95% CI]Odds ratio (95% CI) ESSENCE [0.58, 1.01] TIMI 11B [0.60, 1.10] INTERACT [0.28, 1.08] A to Z [0.68, 1.67] SYNERGY [0.68, 1.05] Overall [0.70, 0.94] Enoxaparin better UFH better Test for heterogeneity: χ 2 = 2.86, df = 4, P = Petersen JL, et al. JAMA. 2004;292: *No prerandomization therapy population.
STRIVE TM At least 2 of 3 required: Age 60 ST (transient) or (+) CK-MB or Troponin IV Heparin n=4985 Primary end point: death or MI at 30 days High-Risk ACS Patients Randomize (N=10,027) Early invasive strategy Other therapy per ACC/AHA Guidelines (ASA, -blocker, ACEI, clopidogrel, GP IIb/IIIa) 60 U/kg 12 U/kg/h (aPTT sec) 1 mg/kg SC q12hr SYNERGY: Study Design Mahaffey KW, et al, for the SYNERGY Investigators. JAMA. 2004;292: No prerandomization therapy population Enoxaparin n=4993
STRIVE TM SYNERGY: Primary End Point Freedom From Death / MI Days From Randomization UFH Enoxaparin HR 0.96 ( ) 30-Day Death/MI Hazard Ratio (95% CI) Enoxaparin Better UFH Better Mahaffey KW, et al, for the SYNERGY Investigators. JAMA. 2004;292: Adapted with permission from
STRIVE TM SYNERGY: Bleeding Events at 30 Days EnoxaparinUFHP value (n=4993)(n=4983) GUSTO severe bleeding Any RBC transfusion TIMI major bleeding: Clinical CABG-related Non–CABG-related Hb drop < % of patients randomized to enoxaparin were switched to UFH 4% of patients randomized to UFH were switched to enoxaparin Mahaffey KW, et al, for the SYNERGY Investigators. JAMA. 2004;292:45-54.
STRIVE TM Moderate- to high- risk ACS ACUITY Study Design: First Randomization Angiography within 72 h Aspirin in all, Clopidogrel dosing and timing per local practice UFH or enox + GP IIb/IIIa n=4603 Bivalirudin + GP IIb/IIIa n=4604 Bivalirudin alone n=4,612 R* Moderate- to high-risk patients with UA or NSTEMI undergoing an invasive strategy (N=13,819) Medical management PCI CABG Stone GW, et al. Am Heart J. 2004;148: *Stratified by preangiography thienopyridine use or administration.
STRIVE TM 11.7%11.8%1.01 ( ) < Risk ratio ±95% CI Risk ratio ±95% CI Primary end point ACUITY: Primary End Point Measures* UFH/Enoxaparin + GP IIb/IIIa vs Bivalirudin + GP IIb/IIIa Net clinical outcome Ischemic composite Major bleeding Bivalirudin + GP IIb/IIIa better UFH/Enox + GP IIb/IIIa better Bival + IIb/IIIa UFH/Enox + IIb/IIIa RR (95% CI) P value (noninferior) (superior) 7.3%7.7%1.07 ( ) %5.3%0.93 ( ) < Upper boundary noninferiority Stone GW, et al. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 11-14, 2006; Atlanta, Georgia. Adapted with permission from *ITT population
STRIVE TM ACUITY: Primary End Point Measures* Bivalirudin alone better UFH/Enox + IIb/IIIa better Risk ratio ±95% CI Risk ratio ±95% CI Primary end point Bival alone UFH/Enox + IIb/IIIa RR (95% CI) Net clinical outcome Ischemic composite Major bleeding Upper boundary noninferiority 11.7%10.1%0.86 ( ) < %7.8%1.08 ( ) %3.0%0.53 ( ) <.001 P value (noninferior) (superior) UFH/Enoxaparin + GP IIb/IIIa vs Bivalirudin alone *ITT population. UFH = unfractionated heparin Stone GW, et al. Presented at: 55th Annual Scientific Session of the American College of Cardiology; March 11-14, 2006; Atlanta, Georgia. Adapted with permission from
STRIVE TM Patients with NSTE ACS, chest discomfort < 24 hours 2 of 3: age >60 y, ST-segment Δ, cardiac markers Patients with NSTE ACS, chest discomfort < 24 hours 2 of 3: age >60 y, ST-segment Δ, cardiac markers Fondaparinux (n=10,057) 2.5 mg SC once daily OASIS-5: Study Design ASA, Clop, GP IIb/IIIa, planned Cath/PCI as per local practice Randomize Enoxaparin (n=10,021) 1 mg/kg SC twice daily Primary: Efficacy: Death, MI, refractory ischemia at 9 days Safety: Major bleeding at 9 days Risk benefit: Death, MI, refractory ischemia, major bleeds 9 days Hypothesis: First test noninferiority, then test superiority Primary: Efficacy: Death, MI, refractory ischemia at 9 days Safety: Major bleeding at 9 days Risk benefit: Death, MI, refractory ischemia, major bleeds 9 days Hypothesis: First test noninferiority, then test superiority Outcomes PCI <6 h: No additional UFH PCI >6 h: IV UFH With IIb/IIIa, 65 U/kg Without IIb/IIIa, 100 U/kg PCI <6 h: IV Fonda 2.5 mg without IIb/IIIa, 0 with IIb/IIIa PCI >6 h: IV Fonda 2.5 mg with and 5.0 mg without IIb/IIIa N=20,078 Yusuf S, et al. N Engl J Med. 2006;354: Adapted with permission from
STRIVE TM OASIS-5: Results Death, MI, or Refractory Ischemia Through Day 9 Major Bleeding Through Day Days Cumulative Hazard Hazard ratio, 1.01 (95% CI, ) Enoxaparin Fondaparinux Days Cumulative Hazard Hazard ratio, 0.52 (95% CI, ) P<.001 Enoxaparin Fondaparinux Adapted with permission from Yusuf S, et al. N Engl J Med. 2006:354: EventFondaparinuxEnoxaparinP Mortality Day 302.9%3.5%.02 Mortality 6 Months5.8%6.5% Day and 6 Month Results % thrombus on catheter (in fonda group) if no UFH given
STRIVE TM Cell Division G1G1 M G2G2 G0G0 CELL CYCLE Resting S Sirolimus X Paclitaxel X Drug-eluting Stents: Cell-Cycle Sites of Action for Sirolimus and Paclitaxel
STRIVE TM Drug-eluting Stents: Freedom From TLR Time After Initial Procedure (months) 100 CYPHER Bare-Metal Stent 93.6% Time After Initial Procedure (months) TAXUS Bare-Metal Stent 90.6% 80.1% % P< TAXUS II, IV, V, VI (n=3,445) RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS (n=1,748) Schampaert et al. Circulation 2005;112;II-650. Stone et al. Circulation 2005;112;II
STRIVE TM Drug-eluting Stents: Freedom From Cardiac Death Time after Initial Procedure (months) TAXUS II, IV, V, VI (n=3,445) RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS (n=1,748) CYPHER Bare-Metal Stent 98.2% 97.8% TAXUS Bare-Metal Stent 98.0% 97.9% P=0.61 P=0.81 Schampaert et al. Circulation 2005;112;II-650. Stone et al. Circulation 2005;112;II-651.
STRIVE TM Drug-eluting Stents: Freedom From MI Time after Initial Procedure (months) TAXUS II, IV, V, VI (n=3,445) RAVEL, SIRIUS, E-SIRIUS, and C-SIRIUS (n=1,748) CYPHER ® Bare-Metal Stent 95.3% TAXUS ® Bare-Metal Stent 93.6% 93.4% % P=0.93P= Schampaert et al. Circulation 2005;112;II-650. Stone et al. Circulation 2005;112;II-651.
STRIVE TM Predictors of Stent Thrombosis in DES Era Premature discontinuation of antiplatelet therapy DES Platform –Polymer (inflammatory, thrombogenic) –Drug (cytotoxic) Mechanical/lesion-specific factors –Incomplete stent apposition –Lesion complexity (bifurcation, AMI, ISR) –Stent length Hypercoaguable conditions –Antiplatelet therapy ‘resistance’ –High platelet reactivity and clot strength Wenaweser P, et al. J Am Coll Cardiol. 2005;45: Gurbel PA, et al. J Am Coll Cardiol. 2005;46: Gurbel PA, et al. J Am Coll Cardiol. 2005;46:
STRIVE TM 2229 patients after successful DES implantation PES 1167 pts 2223 stents SAT 4 (0.4%) SAT 10 (0.9%) LST 5 (0.5%) LST 10 (0.9%) Total SES 9 (0.9%) Total PES 20 (1.7%) 9.3 5.6 months Total DES 29/2229 (1.3%) P=0.5 P=0.3 P= 4.4 m7.9 3.6 m SES 1062 pts 2272 stents Milan/Siegburg Experience Iakovou I, et al. JAMA. 2005;293:
STRIVE TM 2.6% 3.2% 3.5% 5.5% 29.0% 2.0% 1.3% 8.7% Unstable angina Prior brachyRx ThrombusDiabetesUnprot. left main BifurcationRenal failure Premature antiplatelet d/c Several patient and lesion subgroups have a higher stent thrombosis rate than identified in RCTs Milan/Siegburg Experience Stent thrombosis after DES (SES or PES) occurred in 29/2229 pts (1.3%) at 9.3 ± 5.6 mos Iakovou I, et al. JAMA. 2005;293:
STRIVE TM BASKET-LATE Trial: Study Design Primary End Point: Composite cardiac death or nonfatal MI between months 7 and 18 Other End Points: - Thrombosis-related events: - angiographically documented stent thrombosis - cardiac death/target vessel MI - TVR 743 PCI patients from BASKET Trial None had target vessel diameter ≥4mm, restenotic lesions, or MACE during the on-clopidogrel phase. Concomitant medications: aspirin indefinitely Pfisterer ME, et al. Presented at ACC, Atlanta, Ga. March 14, 2006; Presentation Adapted with permission from BMS Group n=244 DES Group n=499
STRIVE TM BASKET-LATE: Primary Composite End Point Pfisterer ME, et al. ACC, Atlanta, Ga. March 14, 2006; Presentation Adapted with permission from Components of primary composite end point: nonfatal MI/cardiac death (%) DESBMS Additional end point of thrombosis-related events (%) P= DESBMS Composite of cardiac death or nonfatal MI (%) P=.01 % Patients MICardiac Death DESBMS P=.04 P=.09 % Patients
STRIVE TM Braunwald E, et al. J Am Coll Cardiol. 2002;40: Long-Term Medical Therapy for UA/NSTEMI: Class I Recommendations Aspirin 75 to 325 mg/d Clopidogrel 75 mg/d when aspirin is not tolerated Combination of aspirin and clopidogrel for 9 months post-UA/NSTEMI β-blocker Lipid-lowering agent and diet in patients with LDL-C >130 mg/dL Lipid-lowering agent if LDL-C after diet >100 mg/dL* ACE inhibitor for patients with CHF, LV dysfunction (EF <.40), hypertension, or diabetes *NCEP ATP III update indicates optional goal of LDL-C < 70 mg/dL.
STRIVE TM CTT Collaboration: Relation Between Proportional Reduction in Incidence of Major Vascular Events and Absolute LDL-C Reduction at 1 Year Cholesterol Treatment Trialists’ Collaborators. Lancet. 2005;366: Proportional Reduction in Event Rate (SE) 50% 40% 30% 20% 10% 0% -10% Major vascular events Reduction in LDL cholesterol (mmol/L)
STRIVE TM TrialPopulationDuration, y Treatment ArmsPrimary End Point PROVE IT- TIMI 22 Post-ACS (N=4162) 2 40 mg pravastatin vs 80 mg atorvastatin Death, MI, UA requiring hospitalization (>30 d), stroke A to ZPost-ACS (N=4497) 2 Placebo (4 mos) then 20 mg simvastatin vs 40 mg simvastatin (1 month) then 80 mg simvastatin CV death, MI, readmission for ACS, stroke TNTStable CAD (N=10,001) 5 10 mg atorvastatin vs 80 mg atorvastatin CHD death, non- procedure-related MI, resuscitation after cardiac arrest, stroke IDEALStable CAD (N=8888) 5 20 mg simvastatin vs 80 mg atorvastatin CHD death, MI, cardiac arrest with resuscitation Cannon CP, et al. J Am Coll Cardiol. 2006;48: Meta-Analysis of CV Outcomes Trials Comparing Intensive vs Moderate Statin Therapy Trial Design and Baseline Characteristics
STRIVE TM Meta-Analysis of CV Outcomes Trials Comparing Intensive vs Moderate Statin Therapy Changes in LDL-C Levels Adapted with permission from Cannon CP, et al. J Am Coll Cardiol. 2006;48: PatientsACSStable CADPooled n %0% 75.5%28.2% PROVE IT- TIMI 22 A-to-ZTNTIDEALPooled* Baseline Standard Intensive LDL-C(mg/dL) Baseline Standard Intensive Prior Statin Use
STRIVE TM Meta-Analysis of CV Outcomes Trials Comparing Intensive vs Moderate Statin Therapy Reduction in Risk of Coronary Death or MI Adapted with permission from Cannon CP, et al. J Am Coll Cardiol. 2006;48: PROVE IT- TIMI 22 A-to-Z TNT IDEAL Total High-dose better High-dose worse Odds Ratio (95% CI) OR, % CI, P= Odds Reduction Event Rates No./Total (%) High DoseStd Dose -17% 147/2099 (7.0) 172/2063 (8.3) -15% 205/2265 (9.1) 235/2232 (10.5) -21% 334/4995 (6.7) 418/5006 (8.3) -12% 411/4439 (9.3) 463/4449 (10.4) -16% 1097/13798 (8.0) 1288/13750 (9.4)
STRIVE TM Safety of Achieving Ultra-Low LDL Event* <40P value Myositis or Myalgia (AE) NS CK > 3x ULN NS CK > 10x ULN NS Rhabdomyolysis 0000NS ALT > 3X ULN NS Wiviott et al. J Am Coll Cardiol. 2005;46: LDL Level
STRIVE TM HOPE HOPE: Adapted with permission from the Heart Outcomes Prevention Evaluation (HOPE) study investigators. N Engl J Med. 2000;342: P<.001 RRR = 22% Follow-up (days) Patients Reaching Composite End Point [MI, Stroke, CV Death] (%) Ramipril Placebo CV Death, MI, or Cardiac Arrest (%) Placebo annual event rate: 2.4% Perindopril Placebo P=.0003 RRR: 20% Years N = 12, EUROPA: Adapted with permission from Fox KM; EUROPA Investigators. Lancet. 2003;362: PEACE: Adapted with permission from Braunwald E, et al; PEACE Trial Investigators. N Engl J Med. 2004;351: No. at Risk Trandolapril Placebo Placebo Trandolapril Incidence of Primary End Point (%) Years After Randomization EUROPA PEACE ACE Inhibitor Trials: Primary End Points
STRIVE TM CHARISMA Study: Overall Population: Primary Efficacy Outcome (MI, Stroke, or CV Death) † † First occurrence of MI (fatal or non-fatal), stroke (fatal or non-fatal), or cardiovascular death. *All patients received ASA mg/day. § The number of patients followed beyond 30 months decreases rapidly to zero and there are only 21 primary efficacy events that occurred beyond this time (13 clopidogrel and 8 placebo). Adapted with permission from Bhatt DL, et al. N Eng J Med. 2006:354: Cumulative event rate (%) Months since randomization Placebo + ASA* 7.3% Clopidogrel + ASA* 6.8% RRR: 7.1% [95% CI: -4.5%, 17.5%] P = 0.22
STRIVE TM CHARISMA Study: Overall Population: Principal Secondary Efficacy Outcome (MI/Stroke/CV Death/Hospitalization) † † First occurrence of MI, stroke, CV death, or hospitalization for UA, TIA, or revascularization. *All patients received ASA mg/day. §The number of patients followed beyond 30 months decreases rapidly to zero and there are only 38 secondary efficacy events that occurred beyond this time (23 clopidogrel and 15 placebo). Placebo + ASA * 17.9% Clopidogrel + ASA * 16.7% RRR: 7.7% [95% CI: 0.5%, 14.4%] P = 0.04 Cumulative event rate (%) Months since randomization § Adapted with permission from Bhatt DL, et al. N Eng J Med. 2006:354:
STRIVE TM CHARISMA Study Overall Population: Safety Results *Adjudicated outcomes by intention to treat analysis. ICH = intracranial hemorrhage. Safety Outcome* – N (%) Clopidogrel + ASA (n=7802) Placebo + ASA (n=7801) RR (95% CI)P value GUSTO Severe Bleeding 130 (1.7)104 (1.3)1.25 (0.97, 1.61)0.09 Fatal Bleeding26 (0.3)17 (0.2)1.53 (0.83, 2.82)0.17 Primary ICH26 (0.3)27 (0.3)0.96 (0.56, 1.65)0.89 GUSTO Moderate Bleeding 164 (2.1)101 (1.3)1.62 (1.27, 2.10)<0.001 Bhatt DL, et al. N Engl J Med. 2006;354:
STRIVE TM CHARISMA Study: Primary Efficacy Results (MI/Stroke/CV Death) by Pre-Specified Entry Category *A statistical test for interaction showed marginally significant heterogeneity (P=0.045) in treatment response for these pre-specified subgroups of patients. † 166 patients did not meet any of the main inclusion criteria but were followed (intent-to-treat analysis). PopulationRR (95% CI) P value Qualifying CAD, CVD or PAD* 0.88 (0.77, 0.998) (n=12,153) Multiple Risk Factors * 1.20 (0.91, 1.59) 0.20 (n=3,284) Overall Population † 0.93 (0.83, 1.05) 0.22 (n=15,603) Clopidogrel + ASA Better Placebo + ASA Better Adapted with permission from Bhatt DL, et al. N Eng J Med. 2006:354:
STRIVE TM CHARISMA: Clinical Implications In the acute setting, prior studies have shown the benefit of dual antiplatelet therapy for 1 year post ACS or PCI For stable patients, CHARISMA failed to demonstrate a reduction in CV death/MI/stroke with dual antiplatelet therapy CHARISMA may suggest differential long-term effects of dual antiplatelet therapy by patient type: –NOT Recommended for Primary Prevention –Potential benefit in Secondary Prevention (CAD, CVD, or PAD) CV death/MI/stroke - 9 events prevented per 1000 patients treated Balanced by 2 severe GUSTO bleeds per 1000 patients treated These data and future trials will help physicians decide which non-acute/stable patients should receive long-term dual antiplatelet therapy Bhatt DL, et al. N Engl J Med. 2006;354:
STRIVE TM Quality Improvement Programs and Critical Pathways
STRIVE TM Why Develop Critical Pathways? “A treatment gap between therapy that is dictated by evidence-based medicine and therapy that occurs in practice is not a deficit of knowledge; rather, it is a deficit of implementation.” Sidney Smith, MD Director, Center for Cardiovascular Science and Medicine, UNC School of Medicine
STRIVE TM Critical Pathways Standardized treatment protocols for the management of specific disorders Developed to optimize and streamline patient care Prevent underutilization of medications, time in ICU/hospital, costs Ensure quality-of-care measures (eg, door-to-drug times) Optimize patient triage Facilitate communication with specialists and PCP post-discharge Enhance patient compliance and outcomes Minimize potential for medical errors Improve compliance with national standards (JCAHO) Adapted from: Cannon CP, O’Gara PT. Critical Pathways in Cardiology. Lippincott Williams & Wilkins; 2001.
STRIVE TM Joint Commission on Accreditation of Healthcare Organizations (JCAHO) 1997: Launched ORYX™ to integrate use of outcomes and other performance measures into accreditation process 2001: Announced 4 initial core measurement areas for hospitals (2 of 4 required): –Acute MI –Heart failure –Community-acquired pneumonia –Pregnancy 2004: New accreditation process (“Shared Visions–New Pathways”) introduced. Hospitals previously collecting 2 of 4 measure sets are now required to collect 3 of 4 measure sets
STRIVE TM JCAHO Quality Measures in MI Hospitals graded on: Antiplatelet therapy in AMI at arrival and discharge -blocker therapy at arrival and discharge ACE inhibitor therapy for LVSD Time to thrombolysis Time to PCI Adult smoking cessation counseling Inpatient mortality
STRIVE TM Why a Hospital-Based System? Patients –Patient capture point –Have patients/family attention: “teachable moment” –Predictor of care in community Hospital structure –Standardized processes/protocols/orders/teams –JCAHO (ORYX and “Shared Visions – New Pathways”) Source:
STRIVE TM Practical Steps to Improve the Use of Evidence-Based Therapies for ACS Develop critical pathways Establish a multidisciplinary team approach (cardiology, ED, primary care, nursing, laboratory) Identify local cardiology and ED “champions” Track adherence to ACC/AHA guidelines Develop educational materials to improve physicians’ knowledge of the guidelines Secure institution’s commitment to improved patient care Identify areas for continuous QI; provide QI tools Elicit ongoing quarterly feedback Cannon CP, et al. Am Heart J. 2002;143:
STRIVE TM Adapted from Cannon CP, O’Gara PT. Critical Pathways in Cardiology. Lippincott Williams & Wilkins; Corbelli J, et al. Critical Pathways in Cardiology. 2003;2: Critical Pathways Begin in Ambulance and Extend to Long-term, Office-based Care EMS ED InpatientDischarge Community
STRIVE TM EMS Reperfusion Checklist: Evaluation of the STEMI Patient Step 1: Has patient experienced chest discomfort for > 15 min and < 12 h? YES NO STOP Step 2: Are there contraindications to fibrinolysis? If ANY of the following are CHECKED, fibrinolysis MAY be contraindicated. Systolic BP greater than 180 mm Hg Diastolic BP greater than 110 mm Hg Right vs left arm systolic BP difference greater than 15 mm Hg History of structural central nervous system disease Recent (< 6 wk) major trauma, surgery (including laser eye surgery), GI/GU bleed Bleeding or clotting problem or on blood thinners CPR greater than 10 min Pregnant female Serious systemic disease (eg, advanced/terminal cancer, severe liver or kidney disease) Significant closed head/facial trauma within the previous 3 months Step 3: Is patient at high risk such that PCI is preferable? Heart rate greater than or equal to 100 bpm Pulmonary edema (rales greater than halfway up) Systolic BP less than 100 mm Hg Systemic hypoperfusion (cool, clammy) □ Yes □ No Adapted from Antman EM, et al. Available at: nical/guidelines/stemi/ index.pdf.
STRIVE TM STEMI Critical Pathways Corbelli J, et al. Critical Pathways in Cardiology. 2003;2: ST-ELEVATION MI (STEMI): EMERGENCY DEPARTMENT ORDERS ALLERGIES DO NOT USE THESE UNSAFE ABBREVIATIONS “U” and “IU” should be unit, “Ug” should be mcg. “QD” should be daily. “QOD” should be every other day. “BIW” should be two times a week. “TIW” should be three times a week, “AU”, “AS”, “OS”, and “OD” should be written out in full. Correct Use of Leading and Trailing Zeros – Always Leading Never Trailing..1 should be 0.1 and 1.0 should be 1 Initial Orders Check all that apply DIAGNOSTICS Stat EKG, obtain old EKG record Repeat stat EKG 60 minutes after initial bolus of Retavase Start Acute Coronary Syndrome Lab Panel: CMP, CBC/diff, PT/INR/aPTT, CK + CK-MB (site specific), Troponin-I, Magnesium, hs-CRP, lipid profile (routine) Stat portable CXR Cardiac monitor and SaO2 monitors Other ______________________________________ ANTI-ISCHEMIC THERAPY Oxygen 2L/minute Nasal Cannula (titrate to keep pulse oximetry saturations > 94%) IV – 0.9 NS: Intermittent Infusion Device KVO ____ ml/hour Opiate: __________________________________ mg IV (suggest Morphine Sulfate) Nitroglycerin Therapy (Hold if patient has taken Sildenafil (Viagra) within 24 hours) NTG 0.4mg SL every 5 minutes X 3 doses or until pain relief or systolic BP < 100 mm Hg NTG paste _______________________inch(es) topically X 1 IV- start NTG infusion at 10 mcg/minute, then titrate as per pharmacy protocol (use 100mg in 250 ml D 5 W) ANTI-THROMBOTIC THERAPY Aspirin 162 mg po (2 chewable 81 mg tablets) ActualWEIGHT____________ kg Estimated lbs ActualHEIGHT ____________ cm Estimated ft
STRIVE TM STEMI Critical Pathways Fibrinolysis Indications 3-hr symptom onset Delay in PCI (door-to-balloon >90 min) Contraindications to PCI: poor arterial access, renal failure, dye allergy Reperfusion Therapy Indications: Chest pain <12 hours, EKG ST-elevations or new left bundle branch block Primary PCI Indications >3-hr symptom onset Presence of cardiogenic shock, CHF, contraindications to fibrinolysis Stat cardiology consult/catheterization lab page Assess for contraindications for fibrinolytic therapy: 1.History of hemorrhagic stroke at any time; other stroke or cerebrovascular event within 1 year 2.Known intracranial neoplasm 3.Active internal bleeding 4.Suspected aortic dissection (consider CT of chest) Reteplase (Retavase) 10 units IV bolus, repeat 10 units IV bolus at 30 minutes HEPARIN THERAPY: (administer simultaneously with Retavase): Unfractionated heparin: ___units IV bolus (1000 units/ml), then ___units/hour IV infusion Note: When using a fibrinolytic (eg, reteplase): Use Cardiac Unfractionated Heparin Nomogram on back of form Eptifibatide (Integrilin) _____ml IV bolus, then ____ml/hr IV infusion (dosing nomogram on back of form) (Dose adjustment based on serum creatinine may be required.) Unfractionated heparin _____ units IV bolus (1000 units/ml), then ______units/hour IV infusion
STRIVE TM Smooth Transition From Acute to Long-Term Management Adapted from the American Heart Association. Get With The Guidelines Follow guidelines Improve communications Ensure compliance Improve quality of care and outcomes Guidelines Primary Care Secondary Prevention Cardiology Acute Care
STRIVE TM Discharge Protocols Enhance communication with patient and between specialist(s) and primary care physicians 1 Medications: aspirin, clopidogrel, ACE inhibitor, β-blocker, statin 1 Diet, exercise, smoking cessation recommendations 1 Patient symptom awareness, “Act in Time” protocol 2 Wallet-/purse-sized copy of ECG 3 Follow-up appointments 1 1.American Heart Association Web site. Get With The Guidelines. Available at: 2.Act in Time to Heart Attack Signs Campaign. Available at: 3.Greenberg DI, et al. J Cardiovasc Manag. 2004;15:16-18.
STRIVE TM Sample Letter to Patient’s PCP at Discharge for UA/NSTEMI Dear Dr. ________________: Your patient, (name), has been discharged on (date) following treatment for ____ days with a diagnosis of acute coronary syndromes (unstable angina ___ or non-ST-segment elevation myocardial infarction ___). Risk stratification at discharge was _______________________. The patient underwent the following procedures: PCI _____ CABG _____ The following medications have been prescribed post-discharge: Aspirin + clopidogrel: Aspirin at a dose of _____ mg/d Clopidogrel at a dose of 75 mg/d Nitrates (________________) at a dose of ______ mg/d Beta-blocker (________________) at a dose of ______ mg/d ACE inhibitor (________________) at a dose of ______ mg/d Calcium channel blocker (________________) at a dose of ______ mg/d Lipid-lowering agent(s)(__________________) at a dose of ______ mg/d Other: ________________________________________________________________ The following counseling concerning risk modification was provided:______________________ Follow-up is strongly recommended in these areas: ___________________________________ If you have questions, please contact me at: telephone_______________ voice mail ____________ _______________________________ Sincerely, (Hospital discharge report attached)
STRIVE TM What Is the Evidence That Critical Pathways Work? UCLA Cardiac Hospitalization Atherosclerosis Management Program (CHAMP) ACC Guidelines Applied in Practice (GAP) initiative AHA “Get With The Guidelines” program CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress ADverse Outcomes with Early Implementation of the ACC/AHA Guidelines)
STRIVE TM CHAMP Study: UCLA Designed to determine whether physician/patient compliance with preventive therapies can be improved through a hospital- initiated program Tracked initiation of aspirin, β-blocker, ACE inhibitor, statins Used preprinted orders, guidelines, lectures, discharge forms Population: patients with symptomatic atherosclerosis treated at university-associated teaching hospital Methods: no specific algorithms used before CHAMP ( ) National guidelines (ACC/AHA, NCEP ATP I and ATP II) used in CHAMP ( ) Evaluation: treatment rates and clinical outcomes pre-CHAMP and CHAMP in patients hospitalized for acute MI Fonarow GC, Gawlinski A. Am J Cardiol. 2000;85(3A):10A-17A. Cardiac Hospitalization Atherosclerosis Management Program
STRIVE TM Discharge Medications at UCLA Compared With 1437 NRMI Hospitals Aspirin β-blockers ACEIStatins /99 Post-CHAMP (UCLA) 00/01 Post-CHAMP (UCLA) 92/93 Pre-CHAMP (UCLA) 94/95 Post-CHAMP (UCLA) 96/97 Post-CHAMP (UCLA) Fonarow GC, et al. Am J Cardiol. 2001;87: [NRMI Hospitals 00/01 (n=154,602)] Nat’l Benchmark Utilization Rate (%) CHAMP Over an 8-Year Period: Rapid and Sustained Improvement, Superior to National Benchmarks
STRIVE TM Adapted from Mehta RH, et al. JAMA. 2002;287: At AdmissionAt Discharge Pre-GAP Post-GAP Aspirin Usage (%) P=.02 P=.002 ACC’s Guidelines Applied in Practice (GAP) Initiative: Impact on Aspirin Usage at Admission and Discharge
STRIVE TM Adapted with permission from Mehta RH, et al. JAMA. 2002;287: Quality Adherence (%) Preintervention No Tool Use Tool Use Postintervention Aspirin β-Blocker LDL-C No. of Ideal Patients P=.004P=.001 Early Quality Indicators and Standard Admission Orders GAP Initiative: Adherence Improves With Tool Use
STRIVE TM GAP Initiative: Changes in Mortality Before and After GAP Project Eagle KA, et al. J Am Coll Cardiol. 2005;46: In-hospital Mortality 30-d Mortality 1-yr Mortality % Baseline Post-GAP P=.017 P=.001 P=.004
STRIVE TM AHA “Get With The Guidelines” Program Components Training materials for hospital staff Patient education materials Assistance in creating multidisciplinary team Secondary prevention guidelines CME workshops Sample materials (care maps, discharge protocols, discharge forms) American Heart Association Web site. Get With The Guidelines. Available at:
STRIVE TM Clinical/Lab: 8 clicks Clinical/Lab: 8 clicks Interactively checks patient’s data with the AHA Guidelines Discharge meds and interventions: 7 clicks Discharge meds and interventions: 7 clicks Demographics: 6 clicks AHA Tool: Simple One-Page, Online Form American Heart Association Web site. Get With The Guidelines. Available at:
STRIVE TM Rehab/ Exercise Baseline4-6 Months9-12 MonthsBenchmark* Intervention Smoking Counsel LDL-CBP Control Proportion of Patients *Benchmarks established by CMS AND NRMI. Reprinted with permission from the American Heart Association Web site. Get With The Guidelines. Available at: Get With The Guidelines 12-Month Pilot Results: 85 New England Hospitals N=1709
STRIVE TM Performance Matters! Association Between Hospital Guideline Adherence and In-hospital Mortality in CRUSADE Adapted with permission from Peterson ED, et al. JAMA.2006;295: NSTE ACS = non-ST-segment elevation ACS; NSTEMI = non-ST-segment elevation MI In-Hospital Mortality, % Hospital Composite Guideline Adherence Quartiles NSTE ACS In-Hospital Mortality, % Hospital Composite Guideline Adherence Quartiles NSTEMI CRUSADE = Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes With Early Implementation of the ACC/AHA Guidelines.
STRIVE TM NRMI. Available at: Get With The Guidelines. Available at: ACC National Cardiovascular Data Registry. Available at: GRACE. Available at: CRUSADE. Available at: REACH. Available at: Importance of Data-Collection Registries Track adherence to guidelines Support local quality-improvement programs Compare practice patterns/outcomes with national benchmarks Comply with regulatory requirements Provide research data Major data-collection registries –NRMI –AHA “Get With The Guidelines” Patient Management Tool –ACC National Cardiovascular Data Registry –GRACE –CRUSADE –REACH
STRIVE TM Conclusions Gap between knowledge of guidelines and practice Several studies show: –Critical pathways interventions improve care and improve patient outcomes Need local champions, implementation plan, and action!
STRIVE TM Your Hospital Needs You As Champions! Introduction to Breakout Session
STRIVE TM Breakout Session Identify a spokesperson/“team leader” for your group Identify a “Champion” who will lead critical pathways implementation at hospital (spokesperson at workshop may or may not be the “Champion”) Review sample pathways in your binder and copies of your own pathways if you have them with you Faculty will circulate and respond to questions during the breakout sessions
STRIVE TM Breakout Session The session will be divided into 3 time periods –Review pathways (15 min.) –Identify barriers to implementation (15 min.) –Develop a plan of action (15 min.) At the end of each period, spokesperson will report progress to the main group
STRIVE TM Breakout Objective #1 (15 minutes) Review the sample critical pathways and tools (last tab in your binder and on the flash drive) If you already have ACS critical pathways for STEMI and UA/NSTEMI: Identify and discuss updates that can be made to your existing pathways If you do not have ACS critical pathways for STEMI and/or UA/NSTEMI: Review the samples and begin planning customized critical pathways for your institution
STRIVE TM Breakout Objective #2 Identify barriers to implementing critical pathways at your hospital and list potential solutions to overcoming them (15 minutes)
STRIVE TM Breakout Objective #3 Develop a short-term and long-term plan to implement your new or updated ACS critical pathways (15 minutes)
STRIVE TM Concluding Remarks
STRIVE TM Conclusions Guidelines for both UA/NSTEMI and STEMI have had updates in antithrombotic therapies and interventions Major gap exists between physicians’ knowledge of guidelines and therapies received by patients Studies show that critical pathways interventions (eg, GAP, CHAMP, GTWG, CRUSADE) –Improve care –Are associated with improved outcomes Participation in national data registries enables multidisciplinary hospital teams to monitor and refine critical pathways and improve outcomes
STRIVE TM Success is Up to You Important to identify/recruit a “Champion” (should be first order of business when you return to the hospital if not established this evening) Begin to assemble multidisciplinary team for pathways development/implementation Establish specific goals with time frames (eg, modify template or existing pathways to include new ACC/AHA Guidelines) Schedule regular meetings to discuss progress Begin to implement the new or revised ACS Critical Pathways -- set a time goal)