CAN WE MANAGE ACS WITHOUT INTERVENTION

Information about CAN WE MANAGE ACS WITHOUT INTERVENTION

Published on August 5, 2014

Author: drvs1994

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Can we manage ACS without intervention? : Can we manage ACS without intervention? Dr.Vinod Sharma National Heart Institute New Delhi Spectrum of ACS : Spectrum of ACS European Heart Journal (2011) 32, 2999–3054 PowerPoint Presentation: Clinical manifestation of CAD is DYNAMIC in nature …… Atherosclerosis: Atherosclerosis Continuous but not a linear process Disease with alternate phase of stability & instability PowerPoint Presentation: Culprit is vulnerability …… Link between CV risk factors, endothelial dysfunction, inflammation & ACS: Link between CV risk factors, endothelial dysfunction, inflammation & ACS CV RISK FACTORS Smoking Diabetes Hypertension Shear stress Oxidative stress Infection ? ENDOTHELIAL DYSFUNCTION INFLAMMATION NFkB ↓ Nitric Oxide, PGI2, TGF ↑ Adhesion molecules (ICAM, VCAM) ↓ Andrenomedullin, CNP ↑ Chemotactic proteins (MCP – 1) ↑ Endothelin – 1, PDGF, ACE ↑ Interleukins, C-reactive protein ↑ Apoptosis, tissue factor PLATELET AGGREGATION, FIBRIN PRODUCTION, PLAQUE GROWTH ACUTE CORONARY SYNDROMES PowerPoint Presentation: Acute Coronary Syndrome a “PANCORONITIS” ? Local manifestation of systemic disease PowerPoint Presentation: Evidence of multiple “vulnerable” plaques in acute coronary syndrome Plaque Rupture – Clinical Manifestation: Plaque Rupture – Clinical Manifestation People who died due to ACS, harbour both thrombosed & non thrombosed ruptured plaques in their coronary arteries. Goldstein JA et al: NEJM 2000 Additional plaques are frequently found adjacent to the culprit lesions in patients undergoing PTCA. Schoenhager Petal: 2003 PowerPoint Presentation: Additional Unstable Plaques Beyond the Culprit Lesion 27 patients with ACS. Angio + 3 vessel IVUS PowerPoint Presentation: Time is essence …… 1. Time is Myocardium 2. Infarct Size is Outcome: B C A Extent of Myocardial Salvage Mortality Reduction (%) D 100 80 60 40 20 0 0 4 8 12 16 20 24 Time From Symptom Onset to Reperfusion Therapy, h Critical Time-dependent Period Goal: Myocardial Salvage Time-independent Period Goal: Open Infarct-Related Artery Gersh BJ, et al. JAMA. 2005;293:979. 1. Time is Myocardium 2. Infarct Size is Outcome PowerPoint Presentation: Every 30-minute delay from onset of symptoms to reperfusion. 1 year mortality is increased by 8% De Luca et al, Circulation 2004 Reduction in Long Term Mortality PowerPoint Presentation: Red Vs White Thrombus …… PowerPoint Presentation: NSTEMI Platelet rich Thrombus Anti-platelet drugs STEMI Fibrin rich Thrombus Thrombolysis / PCI PowerPoint Presentation: Myocardial perfusion, not the epicardial perfusion is the final determinants…… PowerPoint Presentation: Illustration of the traditional concept of microcirculatory impairment in the setting of no flow in the proximal LAD compared with preserved flow in the left circumflex coronary artery, as typically seen in acute anterior ST-segment elevation myocardial infarction (upper left panel). Lerman A et al. Eur Heart J 2007;28:788-797 PowerPoint Presentation: The non-traditional concept centres on the vulnerable patient, taking into account primary dysfunction of the microcirculation of a vulnerable myocardium in addition to the vulnerable plaque, which contributes to the clinical presentation and outcome. Lerman A et al. Eur Heart J 2007;28:788-797 PowerPoint Presentation: “ Despite the proven success of restoration of epicardial coronary blood flow in a reasonably timely fashion, reperfusion on the myocardial level is not accomplished in ~50% of patients with STEMI and is of negative prognostic implication” Lerman et al; European Heart Journal 2007 NSTEMI ACS : NSTEMI ACS Guidelines for treatment of ACS : Guidelines for treatment of ACS Anti-ischemic drugs [ class I] Oral or intravenous nitrate in unstable angina Oral beta blocker therapy should be continued CCBs for vasospastic angina Antiplatelet drugs [class I] Aspirin loading dose [300 mg] followed by maintenance dose of 75-150 mg per day P2Y 12 therapy should be given as loading dose followed by maintenance dose over 12 months period Guidelines for treatment of ACS : Guidelines for treatment of ACS GpIIb / IIIa inhibitors Combination of antiplatelet , GpIIb / IIIaI and anticoagulant should be decided based on bleeding and ischemic risk. Combination with dual antiplatelet therapy is indicated before PCI in high risk patients if the bleeding risk is very low. Anticoagulants Recommended in all patients in addition to antiplatelet therapy Anticoagulant should be selected based on the bleeding and ischemic risk Fondaparinux 2.5 mg daily SC has the most favourable efficacy and safety profile. Alternatively enoxaparin or UFH can be used. Anticoagulation should be maintained up after hospital discharge UFH or bivalirudin (in high risk cases) should be added to GpIIb / IIIa I before PCI. Management of NSTEMI ACS : Management of NSTEMI ACS Based on: Responsiveness to antianginal treatment. Routine clinical chemistry, particularly troponins (on presentation and after 6–9 h) and other markers, according to working diagnoses (e.g. D- dimers , BNP, NT- proBNP ); if highly sensitive troponin assays are available, a fast track rule-out protocol (3 h) may be implemented Repeat or continuous ST-segment monitoring (when available). Ischaemic risk score assessment (GRACE score). Echocardiogram Check list for treatment in ACS European Heart Journal (2011) 32, 2999–3054 GRACE score : GRACE score GRACE risk score provides the most accurate stratification of risk both on admission and at discharge due to its good discriminative power Calculations can be done using personal digital assistant software or performed online (http://www.outcomes.org/grace) European Heart Journal (2011) 32, 2999–3054 Indications for invasive management : Indications for invasive management aRise/fall of troponin relevant according to precision of assay. CABG = coronary artery bypass graft; eGFR= estimated glomerular filtration rate; GRACE = Global Registry of Acute Coronary Events; LV = Left ventricular; PCI = percutaneous coronary intervention European Heart Journal (2011) 32, 2999–3054 NSTEMI ACS - Whether to go for invasive strategy and when?: NSTEMI ACS - Whether to go for invasive strategy and when? Conservative strategy (no or elective angiography) Following patients may be regarded as low risk and should not routinely be submitted to early invasive evaluation No recurrence of chest pain. No signs of heart failure. No abnormalities in the initial ECG or a second ECG (at 6–9 h). No rise in troponin level (at arrival and at 6–9 h). No inducible ischaemia . European Heart Journal (2011) 32, 2999–3054 Invasive vs. Conservative strategy : Invasive vs. Conservative strategy A meta-analysis of FRISC-2, Invasive versus Conservative Treatment in Unstable Coronary Syndromes (ICTUS), and Randomized Intervention Trial of unstable Angina-3 (RITA-3) studies compared routine invasive vs. selective invasive strategy for ACS patients There was reduction in 5-yrs mortality risk in patients undergoing routine invasive management which was most significant for high risk patients 2.0–3.8% absolute reduction in cardiovascular death or MI in the low and intermediate risk groups, and an 11.1% absolute risk reduction in the highest risk patients (diabetic patients, the elderly, patients with renal insufficiency) European Heart Journal (2011) 32, 2999–3054 TIMACS (Timing of Intervention in Acute coronary Syndrome): TIMACS (Timing of Intervention in Acute coronary Syndrome) Non significant trend towards reduced incidence of primary end point (New MI, death, stroke with in 6 months) 11.3% delayed group Vs 9.6% in early intervention group. Patients in highest tertile of GRACE Risk Score (> 140) experienced significant reduction in primary endpoint. No difference in outcome (6.7% delayed Vs 7.6% early intervention) among patients in lower 2 risk tertile (GRACE Score < 140). ABOARD (Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndrome) – JAMA 2009: ABOARD (Angioplasty to Blunt the Rise of Troponin in Acute Coronary Syndrome) – JAMA 2009 (Immediate Vs Delayed CAG & PCI) N = 352 Background anti-thrombotic therapy. Primary Endpoint – Peak Troponin I during the hospitalization Secondary Endpoint – Death, MI, urgent revascularization by 1 month Result : 1) No advantage with regard to the primary endpoint. 2) No improved outcome in the pre-specified secondary endpoints. PowerPoint Presentation: STEMI represents the critical phase of Acute Coronary Syndrome ST Elevation MI PowerPoint Presentation: AMI Therapy : A stunning Evolution !! Best of Angioplasty Techniques Multifacelated Approach + Adjunctive Medication Angioplasty Thrombolysis CCU Bed Rest “Brave New world” Dark-Ages Reperfusion is the key to save myocardium and life….: Reperfusion is the key to save myocardium and life…. Aim is to open the blocked I.R.A. and Re-establish the coronary blood flow A . Rapid B . Early C . Complete D . Sustained PowerPoint Presentation: PTCA vs. Fibrinolysis: Short Term Clinical Outcomes (23 RCTs) PTCA Frequency (%) Keeley E. et al., Lancet 2003; 361:13-20. P=0.0002 P=0.0003 P<0.0001 P<0.0001 P<0.0001 P=0.0004 P=0.032 P<0.0001 Death Death, no SHOCK data ReMI Rec. Isch Stroke Hem. Stroke Major Bleed Death MI CVA Fibrinolysis N = 7739 PowerPoint Presentation: Lytic Vs. PCI in Acute MI Patients Fibrinolysis Primary Angioplasty 0% 50% 100% >95% TIMI 3 0.1% Stroke 2% Reocclusion 5% availability 100% 50% 0% 60% TIMI 3 <50% Treated 1% Stroke 5% Reocclusion Availability 25% Late occlusion Selection of Reperfusion Strategy in STEMI: Selection of Reperfusion Strategy in STEMI Time since the onset of symptoms Risk of Mortality from STEMI Availability of skilled PCI Laboratory Time required for Transport Any contraindication to thrombolysis including bleeding, ICH Patient preference ACC/AHA STEMI Guidelines 2004 Time vs In-hospital Mortality - DTB Time: NRMI–3/4: Time vs In-hospital Mortality - DTB Time: NRMI–3/4 McNamara RL, JACC, 2006 N = 29,222 P < .001 Time Delay to Treatment and Mortality in Primary Angioplasty for Acute Myocardial Infarction Every Minute of Delay Counts: Time Delay to Treatment and Mortality in Primary Angioplasty for Acute Myocardial Infarction Every Minute of Delay Counts Every minute of delay in primary angioplasty for STEMI affects 1-year mortality, even after adjustment for baseline characteristics. Therefore, all efforts should be made to shorten the total ischemic time, not only for thrombolytic therapy but also for primary angioplasty. Circulation 2004 Superiority of 1° PCI Over Lysis Lost After a DB − DN Delay of 114 Minutes : Superiority of 1 ° PCI Over Lysis Lost After a DB − DN Delay of 114 Minute s Pinto DS, et al. Circulation. 2006;114:2019-25 . PCI Related Delay (DB − DN) (min) PCI Better Odds of Death 0.8 1.25 1.5 0.5 1.0 2.0 120 60 75 90 105 135 150 165 180 114 Fibrino-lysis Better PowerPoint Presentation: 95.8% of patients treated after 90 minutes Door to balloon Door to door Indian scenario: Indian scenario Pain to door time: South India: 10.8 hours (Indian Heart J 2004;56: 210–4) North India: 5.2 hours (Indian Heart J 2003;55: 349–53) Door to drug time: 1 hour Low rate of in-hospital thrombolysis mainly due to late arrival. Reasons for not receiving in-hospital thrombolysis 30days mortality among 1320 pts 16.9% Selection of Reperfusion Strategy in STEMI: Majority of the hospitals are not PCI enabled. Most of PCI enabled hospitals do not have inhouse interventional Cardiologists & paramedics to carry out interventional procedures round the clock. Availability of transport, long transportation time, traffic congestion & weather condition affects access to the PCI enabled centre. Selection of Reperfusion Strategy in STEMI PowerPoint Presentation: Accounts / Billing section Your patient needs PPCI. Deposit Rs.2.0 lacs immediately for PCI From where, I get 2.0 lacs at this time in night !!! Time to Treatment for Lytics (McNamara, RL 2007 AJC 100:1227): Time to Treatment for Lytics (McNamara, RL 2007 AJC 100:1227 ) Benefit of Thrombolytic Therapy is Greatest in Patients Treated Within Few Hours of Symptom Onset: Benefit of Thrombolytic Therapy is Greatest in Patients Treated Within Few Hours of Symptom Onset 50,246 AMI patients randomized to lytic vs control Boersma E et al. Lancet 1996;348:771 PowerPoint Presentation: USIC. Circulation 2004;110:1909-1915 n = 1,922 Benefits of Early Administration of Thrombolytics CAPTIM trial: Pre-hospital thrombolysis within 2 hours is superior to Primary PCI: CAPTIM trial: Pre-hospital thrombolysis within 2 hours is superior to Primary PCI Similar mortality for primary percutaneous coronary intervention and a policy of pre-hospital lysis followed by transfer to an interventional center. In addition, for patients treated within 2 h of symptom onset, 5-year mortality was lower with pre-hospital lysis. European Heart Journal (2009) 30, 1598–1606 PowerPoint Presentation: USIC 2000, French Registry Data Hospital administered ‘lysis as good as PCI EURO-PCR Paris 2003 Pre hospital lysis French USIC 2000 survey: real world: French USIC 2000 survey: real world No reperfusion Pre-hosp TT Hosp TT Primary PCI Patients 386 (30%) 155 (12%) 322 (25%) 425 (33%) Age (year) 71 60 61 61 Time to admission (h) 2.8 2.4 2.2 2.1 1 year death 14.7% 3.2% 9.0% 7.9% USIC. Circulation 2004;110:1909-1915 PowerPoint Presentation: Mehta, Textbook of STEMI Interventions Ease of Use; Favorable Pharmacokinetics; bri Highest Reperfusion rates; Agent most used in Clinical Trials Tenecteplase: Advantages: Tenecteplase : Advantages Ease of administration – anytime, anywhere Rapid action – saves myocardium More potent than alteplase Weight adjusted dosing – prevents over / under dosing No effect on platelet aggregation, reducing reocclusion Fibrin specificity – reduces bleeding Reduced plasma clearance – long half-life – single dose High PAI-1 resistance – stays longer in blood Less incidence of bleeding than alteplase Best suited for pre-hospital thrombolysis . PowerPoint Presentation: INDIAN REGISTRY* UPDATED: 20.09.2009. PATIENT’S DATA RECORDED = 2100 * Prescription event monitoring as part of Pharmacovigilance PowerPoint Presentation: ELAXIM INDIAN REGISTRY PowerPoint Presentation: ELAXIM INDIAN REGISTRY Adverse events reported Indian Registry ASSENT-2 Any bleeding (excluding ICH*) 4.62% 21.76% ICH (without GpIIb / IIIa inhibitors) 0.48% 0.93% Stroke (Non-ICH) 0.24% 1.78% Myocardial re-infarction 3.33% 4.10% Ventricular arrhythmias 5.71% 20.5% Mortality (All cause) 3.48% 6.18% * ICH = Intracranial hemorrhage PowerPoint Presentation: ACC/AHA Guidelines for Management of Patients With STEMI, 2007/ Update 2011 Reperfusion Options for STEMI Patients If presentation is < 3 hours and there is no delay to an invasive strategy, there is no preference for either strategy. ACC/AHA Guidelines for Management of Patients With STEMI, Journal of the American College of Cardiology 2007/2011 On-site FT better than delayed PCI : On-site FT better than delayed PCI PCI-related delays are extensive among patients transferred for transfer for PCI (X-PCI) and are associated with poorer outcomes. No differential excess in mortality was seen with X-PCI compared with on-site fibrinolysis (O-FT) even with long PCI-related delays, but as XDB door-to-needle time times increase, the mortality advantage for X-PCI over O-FT declines Circulation . 2011;124:2512-2521 Timely reperfusion is the more important than the choice of reperfusion : Timely reperfusion is the more important than the choice of reperfusion The timeliness of treatment with either PPCI or thrombolysis as per ACC 2007 guidelines is a strong predictor of overall mortality . However, no association is observed with choice of reperfusion therapy. Untimely PPCI has worse prognosis than timely fibrinolysis and untimely fibrinolysis has poor prognosis than timely PPCI. JAMA 2010, 303 (21): 2148-55 : Despite the clinical superiority of PAMI , thrombolytic therapy is the default treatment in many countries due to the practical limitations of PAMI Fibrinolysis Vs PPCI – “Real World Applicability”: Fibrinolysis Vs PPCI – “Real World Applicability” Country Fibrinolysis PPCI Canada & 66% 2.5 – 11% Western Europe UK 71.6% 11 – 21% Germany 36 – 42% 10 – 25% France 32 – 45% 13 – 18% Israel & 35 – 45% 11 – 17% Scandinavia Australia & 43 – 53% 8.7 – 17.4% New Zealand Eur J Clin Pharmacol 2009 Emerging Modalities: Emerging Modalities Pharmacoinvasive Management (PCI following TNK) is a better , safer option than PAMI as proved recently . JACC Sept 2007 It widens the time window for PCI This seems to combine the benefits of Mechanical and pharmacological strategies in reperfusion PowerPoint Presentation: ‘Best of both worlds’ : Local rapid cheap Thrombolysis to majority & PCI Routinely PowerPoint Presentation: Results Early PCI within 6 hrs after thrombolysis was associated with a 6% absolute reduction in the primary study composite endpoint . Standard 16.6% vs Pharmacoinvasive 10.6% (OR = 0.0013 = 0.537 [.368, 0.783]: p = 0.0013 (Figure) Conclusions Challenges findings of older studies regarding timing of fibrinolysis and PCI Pharmacoinvasive strategy was safe and effective Findings provide important information for shaping future guidelines TRANSFER-MI Trial Design: TRANSFER-MI was a randomized study comparing pharmacoinvasive strategy (transfer to PCI center for routine early PCI within 6 hrs) with standard treatment (early transfer only for failed reperfusion) for high-risk STEMI patients receiving thrombolysis at non-PCI centers (N=1,060). The primary endpoint was 30-day composite of death, reinfarction, recurrent Ischemia, CHF, shock. Standard Pharmacoinvasive 30 Day Composite (death, reinfarction, recurrent ischemia, CHF, shock) OR = 0.537 p =0.0013 Kastrani, K et al. Presented at ACC, 2008 @2008, American Heart Association. All rights reserved. % of pts Patients 1060 NORDISTEMI: NORDISTEMI Objective : To compare a strategy of immediate transfer for percutaneous coronary intervention (PCI) with an ischemia-guided approach after thrombolysis in patients with very long transfer distances to PCI. (J Am Coll Cardiol 2010;55:102–10) NORDISTEMI: NORDISTEMI (J Am Coll Cardiol 2010;55:102–10) PowerPoint Presentation: Studies (year) & Total randomized, n Major Inclusion Criteria Time from Lysis to routine early PCI (h) 30 day composite of mortality / re-infarction / ischaemia , N (%) Lysis + routine early PCI Lysis + ischaemia -guided PCI NORDI-STEMI 19 (2005-2008) & 266 Symptoms of MI present for < 6 h, ST- elevation, expected time delay to PCI > 90 min, tenecteplase use 2.7 (median) 13(10) 26 (20) TRANSFER-AMI 18 (2004-2007) & 1059 Symptoms of MI present for < 12 h and ST-elevation. Only tenecteplase -treated patients used < 6 (3.9 median) 39 (7) 58 (11) WEST 17 (2005) & 204 Age > 18 years, not pregnant Symptoms presumed secondary to STEMI lasting at least 20 min and ST-elevation / new LBBB < 24 (4.9 median) 10 (10) 13 (13) CARESS-AMI 15 (2002 – 2007) & 600 Symptoms of MI present for < 12 h and ST-elevation / new LBBB/ Killip class > 2/LV ejection fraction < 30% < 3 (2.2 median) 13 (4) 32 (11) CAPITAL – AMI 14 (2001-2004) & 170 Presentation < 6 h of onset of chest discomfort of > 30 min duration and ST-elevation / LBBB < 3 (1.6 median) 12 (14) 29 (35) SUMMARY OF STUDIES PowerPoint Presentation: Studies (year) & Total randomized, n Major Inclusion Criteria Time from Lysis to routine early PCI (h) 30 day composite of mortality / re-infarction / ischaemia , N (%) Lysis + routine early PCI Lysis + ischaemia -guided PCI GRACIA-I 13 (2000-2001) & 500 Chest pain lasting 30 min to 12 h and ST-elevation / LBBB < 24 [16.7 mean (SD 5.6)] 12 (5) 16 (6) SIAMI III 11 (1998 – 2001) & 197 Symptoms of MI present for < 12 h + ST – elevation Eligible for thrombolysis No secondary / iatrogenic MI < 6 (3.5 + 2.3) 7 (8) 25 (31) PRAGUE – I 10 (1997 – 1999) & 199 Within 6 h of symptom and ST- elevation / LBBB Present to community hospital sans PCI facility < 1.1 (n/a) N/A N/A Pooled (1997-2007) & 3195 < 24 106 (7.3) 199 (13.5) SUMMARY OF STUDIES ESC Guidelines 2008: ESC Guidelines 2008 Conservative Vs Invasive Management of ACS: Conservative Vs Invasive Management of ACS Thrombolysis PCI Availability - Expertise - Timely fashion    X X X Adressing the systematic issue  X Cool of period  X Stent thrombosis X  Re-occlusion / Re-infarction  X Re- stenosis in follow up (within 6 months) X  Cost effectiveness  X Infrastructure demand X  PowerPoint Presentation: Absolute mortality rate remains same For last 15 years 5.5% in young and 19.7% in elderly PowerPoint Presentation: “One Size fits all” Summary : Summary Patients presenting with chest pain should be rapidly categorized to STEMI, NSTEMI ACS or ACS unlikely categories Majority of NSTEMI ACS patients with low & intermediate risk can be treated conservatively. In high risk cases such as diabetic patients, the elderly, patients with renal insufficiency invasive evaluation followed by PCI is recommended. Summary : Summary For STEMI patients, immediate reperfusion is most important irrespective of the mode Early thrombolysis can provide better efficacy than delayed PPCI in STEMI Prehospital thrombolysis is more feasible strategy in developing countries where there can unacceptable delay during patient transfer Pharmacoinvasive approach has results comparable to timely performed PPCI and allows time for transfer of patient to a PCI centre Time is Essence: Time is Essence Early Diagnosis Risk Stratification Rapid Reperfusion Acute Coronary Syndrome: Acute Coronary Syndrome Time is Muscle & Muscle is Life

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