Optimal Timing of PCI in ACS Patrick Hildbrand

Trends and Prognosis in ACS Furman MI, JACC 2001, 37: Hospital 1 year

ACC/AHA 2007 STEMI GUIDELINES Focused Update /2007 ACC/AHA PCI GUIDELINES Focused Update /2007 ESC GUIDELINES FOR THE DIAGNOSIS AND TREATMENT OF NON-ST-SEGMENT ELEVATIONAUTE CORONARY SYNDROMS06/2007 Optimal Timing of PCI in ACS

4 Class I Benefit >>> Risk Procedure/ Treatment SHOULD be performed/ administered Class IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Class IIb Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class III Risk ≥ Benefit No additional studies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL should is recommended is indicated is useful/effective/ beneficial is reasonable can be useful/effective/ beneficial is probably recommended or indicated may/might be considered may/might be reasonable usefulness/effectiveness is unknown /unclear/uncertain or not well established is not recommended is not indicated should not is not useful/effective/beneficial may be harmful Applying Classification of Recommendations and Level of Evidence

5 Class I Benefit >>> Risk Procedure/ Treatment SHOULD be performed/ administered Class IIa Benefit >> Risk Additional studies with focused objectives needed IT IS REASONABLE to perform procedure/administer treatment Class IIb Benefit ≥ Risk Additional studies with broad objectives needed; Additional registry data would be helpful Procedure/Treatment MAY BE CONSIDERED Class III Risk ≥ Benefit No additional studies needed Procedure/Treatment should NOT be performed/administered SINCE IT IS NOT HELPFUL AND MAY BE HARMFUL Applying Classification of Recommendations and Level of Evidence Level A: Recommendation based on evidence from multiple randomized trials or meta-analyses Multiple (3-5) population risk strata evaluated; General consistency of direction and magnitude of effect Level B: Recommendation based on evidence from a single randomized trial or non-randomized studies Limited (2-3) population risk strata evaluated Level C: Recommendation based on expert opinion, case studies, or standard-of-care Very limited (1-2) population risk strata evaluated

Therapeutic Options Anti-ischemic agents Anti-coagulants UFH or LMWH Factor-Xa inhibitors (Fondaparinux) Direct Thrombin inhibitors (Bivalirudin) Anti-platelet agents ASA Clopidrogel GP IIb/IIIa Inhibitors Revascularization ACS

Trends and Prognosis in ACS Diagnosis and Risk assessment of ACS Therapeutic Options > Timing Revascularization Summary Management Strategy Optimal Timing of PCI in ACS

Chest Pain

ECG Kaul P, JACC 2001, 38:64-71

Biochemistry

Risk Stratification

Summary Diagnosis and Risk assessment Diagnosis and short-term risk stratification should be based on a combination of Clinical history Symptoms ECG and (10 minutes, 6h, 24h and before hospital discharge) Biomarkers (admission and after 6-12 h) Risk score results Echocardiography is recommended to rule out differential diagnosis Patient without recurrence of pain, normal ECG findings and negative troponins tests > non invasive stress testing

Trends and Prognosis in ACS Diagnosis and Risk assessment of ACS Therapeutic Options Summary Management Strategy Optimal Timing of PCI in ACS

Coronary revascularization Revascularization for ACS is performed to RELIEVE ANGINA RELIEVE ONGOING MYOCARDIAL ISCHEMIA PREVENT PROGRESSION TO MI OR DEATH

15 Acute Coronary Syndromes UA/NSTEMI STEMI Optimal Timing of PCI in ACS Primary PCI Rescue PCI Facilitated PCI Delayed PCI

16 Primary PCI STEMI patients presenting to a hospital with PCI capability should be treated with primary PCI within 90 min of first medical contact as a systems goal.

Primary PCI versus Fibrinolysis

Primary PCI versus fibrinolysis for MI Meta analysis of 23 trials Keeley EC. Lancet 2003;361:13-20 P<0.0001

Defeated

CAPTIM: Mortality at different time points Mortality Pre- hospital* fibrinolysis Primary PCI p- value Patients At 30 days3.8%4.8%0.29 At 1 year5.4%7.3%0.08 * 26% of patients had rescue PCI Steg PG. Circulation 2003;108:

Time to randomisation and one-year mortality in CAPTIM < 2 h  2 h p = 0.05 p = 0.34 Lysis pPCI Lysis pPCI Steg PG. Circulation 2003;108:

22 Fibrinolytic Therapie STEMI patients presenting to a hospital without PCI capability, and who cannot be transferred to a PCI center and undergo PCI within 90 min of first medical contact, should be treated with fibrinolytic therapy within 30 min of hospital presentation as a systems goal, unless fibrinolytic therapy is contraindicated.

Facilitated PCI

Meta-analysis: Facilitated PCI vs Primary PCI 1.03 ( ) 3.07 ( ) 1.43 ( ) 1.03 ( ) MortalityReinfarctionMajor Bleeding Fac. PCI Better PPCI Better Fac. PCI Better PPCI Better Fac. PCI Better PPCI Better Keeley E, et al. Lancet 2006;367: ( ) 1.71 ( ) 1.51 ( ) Lytic alone N=2953 IIb/IIIa alone N=1148 Lytic +IIb/IIIa N=399 All (N=4500) 1.40 ( ) 1.81 ( )

A planned reperfusion strategy using full-dose fibrinolytic therapy followed by immediate PCI is not recommended and may be harmful. Facilitated PCI using regimens other than full-dose fibrinolytic therapy might be considered as a reperfusion strategy when all of the following are present: a. Patients are at high risk, b. PCI is not immediately available within 90 minutes, and c. Bleeding risk is low (younger age, absence of poorly controlled hypertension, normal body weight). Facilitated PCI

Further Studies Ongoing Prehospital fibrinolytic therapy Better anticoagulant and antiplatelet therapy Use in circumstances of longer delays to PCI However, based on available data, facilitated PCI offered no clinical benefit, and was associated with harm when full dose fibrinolytics were used. D e f e at e d

Options for Transport of Patients With STEMI and Initial Reperfusion Treatment EMS Transport Onset of symptoms of STEMI EMS Dispatch EMS on-scene Encourage 12-lead ECGs. GOALS Sion SZO Inter- Hospital Transfer Golden Hour = first 60 min. Total ischemic time: within 120 min. PatientEMSEMS transport EMS-to-balloon within 90 min. Patient self-transport Hospital door-to-balloon within 90 min. Dispatch 1 min. 5 min. ECG Triage

Late PCI

Occluded Artery Trial (OAT) Eligibility: Total IRA occlusion 3-28 days (>24 hours) Death, MI, CHF Class IV Fatal and Non fatal MI 4 year event rate: n.s. Hochman JS, et al. Am Heart J 2005;150:627-42; Hochman JS, et al. N Engl J Med 2006;355: Exclusion criteria: Significant left main or 3 vessel CAD Hemodynamic or electrical instability Rest or low-threshold angina NYHA Class III-IV HF or shock RESULTS 2166 randomized 1082 PCI + optimal medical therapy 1084 Optimal medical therapy (MED)

PCI of a hemodynamically significant stenosis in a patent infarct artery > 24 hours after STEMI may be considered as part of a invasive strategy. PCI of a totally occluded infarct artery > 24 hours after STEMI is not recommended in asymptomatic patients with 1- or 2-vessel disease if they are hemodynamically and electrically stable and do not have evidence of severe ischemia. Late PCI after Fibrinolysis or for Patients Not Undergoing Primary Reperfusion

Acute Coronary Syndromes UA/NSTEMI STEMI Routine Invasive ( Timing) Selective Invasive Optimal Timing of PCI in ACS

Coronary revascularization

Randomized trials comparing early invasive (dark bars) vs. conservative strategy (open bars)

Invasive vs. Conservative Strategies New data coming from long-term follow up of RITA-3 and FRISC-2 and Mehta meta-analysis show significant risk reduction for death and „death & MI“ at long-term follow up Early hazard shown in ICTUS Trial Early hazard shown in Mehta meta-analysis ICTUS, Lancet 2007 FRISC 2, Lancet 2000 RITA 3 Lancet 2005 Metha JAMA 2005

Timing of Intervention NSTEMI Few studies have shown superiority of very early intervention vs. deferred intervention ISAR-COOL (small sample size) JAMA 2003 VINO Many trials have shown early hazard with early intervention vs. deferred intervention ICTUS trial NEJM 2005 Mehta meta-analysis JAMA 2005 Grace and Crusade registries Heart 2007, Arch Intern Med 2006 > Timing of intervention recommended on the basis of risk stratification

Clinical Outcomes for Patients Stratified by Age (Invasive Vs Conservative Strategies) from TACTICS– TIMI-18 Trial

Outcomes According to Degree of Renal Function Impairment in NSTE- ACS Patients in GRACE Registry Special Conditions & Populations chronic Kidney Disease

Special Conditions& Populations Diabetes Treatment Effect on 30-day Mortality Among Diabetic Patients with NSTEMI from Six Randomized Clinical Trials

Special Conditions& Populations Diabetes

Risk Stratification

Options for Transport of Patients With NSTEMI and Initial Reperfusion Treatment EMS Transport Onset of symptoms of STEMI EMS Dispatch EMS on-scene Encourage 12-lead ECGs. GOALS Sion SZO Inter- Hospital Transfer PatientEMSDiagnosis before treatment Risk stratification Dispatch 1 min. 5 min. ECG Triage Urgent Early No Transfer

Summary Management Strategy