Acute Coronary Syndromes and the Role of Critical Pathway Christopher Cannon, M.D. Brigham and Women’s Hospital Boston

Aspirin and Thrombolysis in Acute MI 35 Day Mortality % of Patients Placebo Aspirin SK Aspirin + SK ISIS-2. Lancet 1988; 2:349-60.

TIMI 2: Effect of Time to Treatment 6 Week Mortality *P=0.05 1 hour faster treatment 6.2 5.2 % of Patients = 3.7 3.2* 10 lives saved per 1000 patients treated 3-4 h 2-3 h 1-2 h <1 h TIMM, et al. Circulation. 1991;84:II-230.

Improving Thrombolysis: t-PA vs. SK TIMI 1: Reperfusion Occluded arteries GUSTO 1: Mortality SK t-PA 80 *P<0.001 *P<0.001 7.3 60 6.3 62 % of Patients 40 31 20 TIMI Study NEJM 1985;312:397-401. GUSTO Inv. NEJM 1993; 329:673-682.

Thrombolysis vs. Primary Angioplasty 30 Day Mortality % of Patients Thrombolysis PTCA t-PA Stent + IIb/IIIa Weaver WD, JAMA 1997; 278:2093-2098. Schomig A, N Engl J Med 2000; 343:385-91

Medical Treatment After MI Mortality During Follow-up % of Patients ISIS-1 Lancet 1986; 2:57-66; HOPE N Engl J Med 2000; 4S. Lancet 1994; 344:1383-1389.

Drug Rx Peri MI: Meta-Analyses 4/22/2017 6:04:54 AM ACUTE MI GUIDELINES 11/96 Drug Rx Peri MI: Meta-Analyses Beta blocker during MI Beta blocker post MI ACEI during MI ACEI post MI if LV dysfxn Nitrates during MI Ca++ blockers Magnesium Lidocaine Class I Antiarrhythmics Number RR Death p value 28,970 24,298 100,963 5,986 81,908 20,342 61,860 9,155 6,300 .87 (.77-.98) .77 (.70-.84) .94 (.89-.98) .78 (.70-.86) .94 (.90-.99) 1.04 (.95-1.14) 1.02 (.96-1.08) 1.38 (.98-1.95) 1.21 (1.01-1.44) 0.02 <0.001 0.006 0.03 NS 0.04 NEJM 335:1662, 1996

Class I Recommendations for Anti-Ischemic Therapy UA/NSTEMI 9/00 Continuing Ischemia/Other Clinical High-Risk Features Bed rest + continuous ECG monitoring 02 to maintain Sa02 >90% NTG IV -Blockers, oral (+IV if high risk) Morphine IV for pain IABP if ischemia or BP ACEI for HTN or  LVEF (possibly all patients) Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.

Class I Recommendations for Antithrombotic Therapy* UA/NSTEMI 9/00 Definite ACS With Continuing Ischemia or Other High-Risk Features† or Planned PCI Likely/Definite ACS Possible ACS Aspirin + IV heparin IV platelet GP IIb/IIIa antagonist Aspirin + Subcutaneous LMWH or IV heparin Aspirin * Clinical data on the combination of LMWH and platelet GP IIb/IIIa antagonists are lacking. Their combined use is not currently recommended. † High-risk features were previously listed; others include diabetes, recent MI, and elevated cardiac TnT or Tnl. Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.

Class I Recommendations: Early Invasive Strategy 1. Early invasive strategy in patients with UA/NSTEMI and any of the following high-risk indicators: a. Recurrent angina/ischemia at rest or with low-level activities despite intensive anti-ischemic rx b. Recurrent angina/ischemia with CHF symptoms, S3 gallop, pulmonary edema, worsening rales, or new or worsening MR c. High-risk findings on noninvasive stress testing d. Depressed LV systolic function e. Hemodynamic instability f. Sustained VT g. PCI within 6 months h. Prior CABG 2. In the absence of these, either an early conservative or an early invasive strategy in hospitalized patients without contraindications for revascularization Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.

Class I Recommendations: Risk Factor Modification UA/NSTEMI 9/00 1. Smoking cessation and achievement or maintenance of optimal weight, daily exercise, and diet 2. HMG-CoA reductase inhibitors for LDL >130 mg/dL 3. Lipid-lowering agent if LDL after diet is >100 mg/dL 4. Hypertension control to a blood pressure of >130/85 mm Hg 5. Tight control of hyperglycemia in diabetes Braunwald et al. J Am Coll Cardiol. 2000;36:970-1062.

GU ARANTEE Implementation of AHCPR Guidelines 4/22/2017 6:04:54 AM GU ARANTEE Implementation of AHCPR Guidelines for Unstable Angina in 1996: Unfortunate Differences Between Women and Men Results from the GUARANTEE Registry

Global Unstable Angina Registry ANd Treatment Evaluation 4/22/2017 6:04:54 AM GU ARANTEE Global Unstable Angina Registry ANd Treatment Evaluation 6 Regions 35 Hospitals 2,948 Patients

GU ARANTEE Medical Management No. Pts ASA (%) Heparin (%) 4/22/2017 6:04:54 AM GU ARANTEE Medical Management No. Pts On Admission ASA (%) Heparin (%) B-blockers (%) At Discharge ASA (or Warfarin) All of above (%) 1788 84 66 53 77 31 Men 1160 80 60 49 69 24 Women 0.018 0.001 0.039 P value 0.016 0.080 0.086 0.007 Adjusted P value

GU ARANTEE Catheterization / Revascularization 1788 53 18 10 59 46 Men 4/22/2017 6:04:54 AM GU ARANTEE Catheterization / Revascularization No. Pts Cath (%) PTCA (%) CABG (%) In Pts Meeting AHCRP criteria Cath (% done) CABG (% done) 1788 53 18 10 59 46 Men 1160 44 12 7% 56 36 Women 0.001 0.002 0.15 0.16 P value 0.004 0.017 0.53 0.05 Adjusted P value

GU ARANTEE Age Medical Management No. Pts ASA (%) Heparin (%) 4/22/2017 6:04:54 AM GU ARANTEE Medical Management Age No. Pts On Admission ASA (%) Heparin (%) B-blockers (%) At Discharge ASA (or Warfarin) All of above (%) 1638 83 64 50 71 28 Age <65 1309 81 62 52 78 Age >65 0.17 0.25 0.46 0.001 0.92 P value 0.24 0.19 0.68 0.003 0.60 Adjusted P value

Non-Q wave MI vs. Unstable Angina 4/22/2017 6:04:54 AM GU ARANTEE Medical Management Non-Q wave MI vs. Unstable Angina No. Pts On Admission ASA (%) Heparin (%) B-blockers (%) At Discharge ASA (or Warfarin) All of above (%) 2600 82 61 49 73 26 UA 300 87 85 63 45 NQWMI 0.031 0.001 P value 0.069 Adjusted P value

Stone PH et al. JAMA 1996;275:1104; Scirica 1999 AHJ GU ARANTEE TIMI III Registry Pre Guideline Post Guideline No. Pts On Admission ASA Heparin B-blockers 1678 82 63 41 Men 1640 77 50 35 Women 1788 84 66 53 1160 80 60 49 Women Comparing Pre- to Post-: Men Women P values : ASA 0.30 0.05 Heparin 0.13 0.001 B-blocker 0.001 0.001 Stone PH et al. JAMA 1996;275:1104; Scirica 1999 AHJ

Giugliano RP,et al. Arch Intern Med 2000;160. 4/22/2017 6:04:54 AM Aspirin within 24 hours 94% 78% P = .002 % survival Weeks post discharge Giugliano RP,et al. Arch Intern Med 2000;160.

Giugliano RP,et al. Arch Intern Med 2000;160. 4/22/2017 6:04:54 AM Heparin within 24 hours 93% 85% P = .06 % survival Weeks post discharge Giugliano RP,et al. Arch Intern Med 2000;160.

Unadjusted One Year Survival 4/22/2017 6:04:54 AM Unadjusted One Year Survival 95% P = .0001 81% Percent surviving Weeks post discharge Giugliano RP,et al. Arch Intern Med 2000;160.

NRMI-2: Distribution of Door-to-Needle Times 4/22/2017 6:04:54 AM NRMI-2: Distribution of Door-to-Needle Times N=84,423 40% Cannon CP ACC 2000

Baseline Characteristics Door-to-needle time (mins) 0-30 31-60 61-90 >90 P value No. Pts 28,176 33,635 11,531 10,244 Age (mean) 61.2 63.5 65.1 65.7 <0.0001 Female (%) 26 34 39 42 <0.0001 Non-white (%) 13 14 16 19 <0.0001 DM (%) 16 20 23 27 <0.0001 Prior MI (%) 16 19 21 21 <0.0001 Anterior (%) 32 34 37 41 <0.0001 HMO (%) 14 13 12 11 <0.0001 Urban Hosp 87 88 87 86 0.0005 Pre-hosp ECG 7 4 3 3 <0.0001 Onset-door (hr) 1.4 1.7 1.9 2.0 <0.0001 (Median)

Door-to-Needle Time vs. Mortality NRMI-2: Thrombolysis Door-to-Needle Time vs. Mortality P=0.0001 P=0.01 P=NS 1.23 1.11 1.03 N=28,624 33,867 11,616 10,316 Cannon CP ACC 2000

Door-to-Balloon Time vs. Mortality NRMI-2: Primary PCI Door-to-Balloon Time vs. Mortality P=NS P=NS P=0.01 P=0.0007 P=0.0003 1.62 1.61 1.41 1.14 1.15 N=2,230 5,734 6,616 4,461 2,627 5,412 Cannon CP, et al JAMA 2000;283:2941-2947.

Distribution of Door-to-Balloon times Door-to-Balloon Time (minutes) 4/22/2017 6:04:54 AM NRMI-2: Primary PCI Distribution of Door-to-Balloon times N=27,080 Door-to-Balloon Time (minutes)

US News and World Report 30-day mortality by hospital category* * 25th, 50th and 75th percentile for each category

US News and World Report Aspirin in ideal candidates

US News and World Report Beta-blockers in ideal candidates

30-day Mortality US News Top-ranked vs Other Hospitals Odds ratio * Adjusted for patient, hospital and physician characteristics

Quality implications The lower mortality observed in “America’s Best Hospitals” appear to be explained in part by their higher use of aspirin and beta-blockers Any hospital can be one of “America’s Best” by increasing their use of aspirin and beta-blockers

EUROASPIRE II European Action on Secondary and Primary Prevention through Intervention to Reduce Events Euro Heart Survey Programme European Society of Cardiology-ESC Wood et al. Lancet 2001; 357: 995-1001  European Society of Cardiology ESC

Therapeutic control of total cholesterol at interview EUROASPIRE % reaching goal* at interview among those using lipid-lowering medication by center * total cholesterol < 5 mmol/l  European Society of Cardiology ESC

% aspirin/other anti-platelets at interview EUROASPIRE by center Wood et al. Lancet 2001; 357: 995-1001  European Society of Cardiology ESC

% beta-blockers at interview by center EUROASPIRE Wood et al. Lancet 2001; 357: 995-1001  European Society of Cardiology ESC

Conclusions EUROASPIRE II A high prevalence of unhealthy lifestyles, modifiable risk factors and inadequate use of prophylactic drug therapies is found in coronary patients across Europe Considerable potential to raise the standard of preventive cardiology exists throughout Europe in order to reduce coronary morbidity and mortality Wood et al. Lancet 2001; 357: 995-1001  European Society of Cardiology ESC

ACUTE CORONARY SYNDROMES 4/22/2017 6:04:54 AM National Heart Attack Alert Program (NHAAP) CRITICAL PATHWAYS FOR THE TREATMENT OF PATIENTS WITH ACUTE CORONARY SYNDROMES I am very pleased to present an overview of the National Heart Attack Alert Program (NHAAP) and to highlight some of its history, educational recommendations, achievements, and future directions. (The speaker may wish to add a personal comment concerning his or her involvement with the program.)

Critical Pathways - Definitions Standardized protocols for care Strict definition Full list of all tasks, tracks variances Broader definition Includes clinical protocols (NHAAP 4D’s) Diagnostic pathways - Chest Pain Centers Treatment pathways - Thrombolysis

Goals of Critical Pathways Increase use of recommended medical therapies (e.g., aspirin) Decrease use of unnecessary tests. Decrease hospital length of stay Increase participation in clinical research Improve patient care and decrease costs.

Need and Rationale for Critical Pathways Underutilization of recommended medications (e.g. Aspirin) Overutilization of procedures Length of stay, # ICU days Quality of care measures (door-to-drug, door-to-balloon times)

Development And Implementation Of Critical Pathways Identify problems ( practice variation) Identify working committee/task force to develop path Distribute draft Critical Pathway to all personnel and departments involved. Revise based on approach. Implement pathway Collect and monitor data on pathway performance. Modify the pathway as needed to further improve performance.

Methods of Implementation of Pathways Specific case manager for each Pt High compliance, high cost Standardized order sheets, Pocket guides “Championing” - Grand rounds Recent study -> similar improvements in care with either formal or simpler pathways (Holmboe, ES et al. Am J Med 1999;107:324-31.)

Goal: < 30 Minutes NHAAP Ann Emerg Med 1994;23:311-29.

W. Rogers, personal communication 4/22/2017 6:04:54 AM W. Rogers, personal communication

Speeding Time to Treatment: Brigham and Women’s Hospital Acute MI Critical Pathway in ED _ _ : _ _ Door Pt. with Chest Pain. ED Arrival Time 10 mins _ _ : _ _ Data Obtain ECG. Assess for ST Elevation 10 mins _ _ : _ _ Decision Assess for Contraindications to Thrombolysis: Active Bleeding Prior Stroke Confirmed BP > 190/110 Major Surgery <2 Mos. Other Major Illness (cancer, etc.) 10 mins NO YES _ _ : _ _ Drug Mix and Give Thrombolytic: Double-Bolus r-PA Primary PCI: 1. Patient with high stroke/bleeding risk Cardiogenic shock (All patients) o Door-to-Drug Time Goal: <30 Mins Cannon CP et al. J Thromb Thrombolysis 1994;1:27-34.

BWH Thrombolysis Critical Pathway: Effect on Door-to-Drug times 4/22/2017 6:04:54 AM BWH Thrombolysis Critical Pathway: Effect on Door-to-Drug times Door-to-Drug Time Pre- Post-Pathway Cannon CP, Clin Cardiol 1999;22:17-22

BWH Thrombolysis Critical Pathway: Initial Experience BEFORE *P=0.013 Cannon CP, et al. Clin Cardiol 1999;22:17-22

4/22/2017 6:04:54 AM PAMI II: Early Discharge Critical Pathway for Low-Risk MI Patients treated with Primary Angioplasty 6 month outcomes Early D/C Standard P value (%) (%) Death 0.8 0.4 NS MI 0.8 0.4 NS Unstable Angina 10.1 12.0 NS D/MI/UA/CHF/stroke 15.2 17.5 NS Length of stay (days) 4.2 7.1 p<0.001 Hospital Costs $9,658 $11,604 p=0.002 + 5,287 + 6,125 slide 4

BWH ED Checklist Orders for UA/NSTEMI Hx. Good Story and/or + ECG, or + CKMB/TnI Hx MI, PCI/CABG Tests  CBC, CMP, PT/PTT CK-MB, TnI  Lipid profile Meds  ASA 325mg chew  Metoprolol IV/PO  Discuss with Cards B - Heparin IV + IIb/IIIa - Enoxaparin SQ - Cath Lab  NTG PRN

Effect of Critical Pathway on Median Length of Stay

CHAMP Program to improve Secondary Prevention Jan 1992- Dec 1995 N=256 pre- and 302 post Pre-CHAMP post-CHAMP D/C 1 yr D/C 1 yr ASA 78% 68% 92% 94% B-blocker 12% 18% 61% 57% ACE 4% 16% 56% 48% Statin 6% 10% 86% 91% LDL <100 6% 58% Fonarow GC et al. Am J Cardiol 2001;87:819-822.

Conclusions Critical pathways hold great promise to improve Quality of care, Clinical outcomes Cost-effectiveness Initial studies show better quality of care and suggest improved outcomes