Thrombolysis, adjunctive pharmacology and interventions

Transcription

1 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation ESC Annual Congress Munich, 2012 Thrombolysis, adjunctive pharmacology and interventions Francisco Fdez-Avilés, MD, PhD Department of Cardiology Hospital General Universitario Gregorio Marañón Complutense University of Madrid School of Medicine NO CONFLICTS OF INTEREST TO DISCLOSE

2 2012 Issues addressed Thrombolytic drugs Angiography and intervention after lysis ( pharmacoinvasive strategy) Adjunctive antithrombotic therapy

3 Deaths per 1000 pts treated ESC Guidelines for STEMI Thrombolysis Evidence Highly effective, but intracranial bleeding in 1% ABSOLUTE MORTALITY REDUCTION - 30 n = FTT. Lancet Delay from onset (hours) Moderate or severe 12% Bleeding GUSTO 1 (N=41021) 14% Hemo. Stroke 11.1% 13.4% 0.46% 0.54% 0.72%* 0.94%** Predictors: Advanced age Low weight Female Hypertension Prior stroke SK + SQH SK + IVH tpa + IVH Combo *P=0.003 vs SK **P<0.001 vs SK

4 Thrombolysis Evidence GUSTO 1 (N=41021) Highly effective, but intracranial bleeding in 1% Better outcome with fibrin-specific agents (t-pa, rt-pa, TNK). TNK: lower rate of non-cerebral bleedings and simple administration (pre-hospital) 7.2% 7.4% 7.0% 6.3%* SK + SQH SK + IVH tpa + IVH Combo *p=0.001vs SK 30-day mortality GUSTO 3 (N=15059) Reteplase Altelplase Death or disabling stroke TNK 7.4% SK Groups *p= deaths +1 stroke /1000 pts treated 6.9%* tpa ASSENT 2 (N=16949) Altelplase 7.24% 7.47% 26.43% P= % 30-day mortality 0.91% 0.87 % ICH 6.18% 6.15% 30-day mortality 0.93% ICH 0.94% Non Cerebral Bleeding P= % 5.45% Transfusion

5 Aborted Infarctions (%) ESC Guidelines for STEMI Thrombolysis Evidence Highly effective, but intracranial bleeding in 1% Better outcome with fibrin-specific agents (t-pa, rt-pa, TNK). TNK: lower rate of non-cerebral bleedings and simple administration (pre-hospital) Higher benefit if administered in < 2 hours and in a pre-hospital basis 35-day mortality according to treatment delay 22 RCTs pts Boersma E. Lancet 1996 ASSENT-ECG N = 727 (Taher T. JACC 2004) Pre-hospital vs In-hospital TL (6 RCTs, N=6434) P= min 162 min P= % 10.23% Time to TL Pre - H JAMA 2000 Mortality In - H

6 Thrombolysis Recommendations

7 Thrombolysis Contraindications CONTRAINDICATIONS TO FIBRINOLITIC THERAPY ABSOLUTE Previous ICH or stroke of unknown origin at any time Ischemic stroke in the preceding 6 months Central nervous system damage, neoplasms or atrioventrcular malformations Recent major trauma/surgery/head injury Gastrointestinal bleeding within the past month Known bleeding disorder Aortic dissection Non-compressible punctures in the past 24 hours RELATIVE TIA in less than 3 months Oral anticoagulants Pregnancy or within 1 week post partum Refractory hypertension (systolic BP >180 mm Hg and/or diastolic BP >110 mm HG) Advanced liver disease Infective endocarditis Active peptic ulcer Prolonged or traumatic resuscitation

8 Thrombolysis Agents and doses

9 Pharmacoinvasive Strategy Evidence

10 Survival Percent survival ESC Guidelines for STEMI Pharmacoinvasive Strategy Evidence Postlysis TIMI & Survival (Cigarroa. AJC 2004) Lysis strongly limited by reopening failure and reocclusion TIMI 2-3 TIMI 0-1 (20-50%) years Postlysis Reocclusion & Survival. (Gibson. JACC 2004) 1 P< No early Re-MI 0,75 Reocclusion-related Re-MI Reocclusion:5-30% Years Years 0,5 0,0 0,5 1,0 1,5 2,0

11 Pharmacoinvasive Strategy Evidence Lysis strongly limited by reopening failure and reocclusion Stone G. Circulation (5 RCTsTrials; N=920) Rescue-PCI is better than conservative treatment or second lysis REACT 4 Primary Composite Endpoint at 6 Months (Death, MI, CVA, or severe heart failure) p<0.001 p= % 29.8% 15.3% Repeat Thrombolysis Rescue PCI Conservative Management

12 Primary Clinical Endpoint* One-year Survival (%) DEATH, RE-MI OR REVASCULARIZATION ESC Guidelines for STEMI Pharmacoinvasive Strategy Evidence Lysis strongly limited by reopening failure and reocclusion Rescue-PCI is better than conservative treatment or second lysis Early routine post-lysis angio/pci is better than watchful waiting strategy and could be equivalent to Primary-PCI (answer ongoing: STREAM, GRACIA-4) 1,0 0,8 0,6 0,4 0,2 0,0 0 GRACIA -1 PRIMARY ENDPOINT AT 1 YEAR GRACIA 2 (N=212) Log rank test = Post-lysis PCI Primary PCI 90.4% 87.9% Time since randomization (months) *: Probability of death, re-mi stroke or ischemia driven revascularization Conservative: 21% Intervention: 9% Hazard ratio 0.44 (95%CI ), p=0.004 Log-rank test: p= Time since randomization (months) EARLY ROUTINE POST-LYSIS PCI ( hh) (8 RCTs, 2 MA, N=3195) Rapid risk stratification Sorter stay Less acute ischemia Less early re-mi Less 1-year MACE FAST AMI (N=1714) p<0.001 Pre-hospital lysis: 94.8% Primary PCI: 91.8% In-hospital lysis: 91.8% No reperfusion: 78% Days

13 Pharmacoinvasive strategy Recommendations

14 Adjunctive therapy to lysis Evidence

15 Adjunctive therapy to lysis Evidence ANTIPLATELETS Better outcome with aspirin plus clopidogrel No evidence with prasugrel or tricagrelor Role of GP 2b/3a unclear 14% Death, re-mi or stroke 11.9% 10% 9.9% 8.8% 9,1% ISIS 2 ASA vs Placebo COMMIT CLARITY Clopidogrel vs Placebo + ASA GRACIA -3 (Tirofiban and DES in postlysis PCI) Full Perfusion Partial perfusion Failed perfusion Major Bleeding 6.1% P= % Tirofiban No Tirofiban Tirofiban No Tirofiban

16 Adjunctive therapy to lysis Evidence ANTIPLATELETS Better outcome with aspirin plus clopidogrel No evidence with prasugrel or tricagrelor Role of GP 2b/3a unclear PARENTERAL ANTICOAGULATION Fibrin-specific lyitcs: UFH improves arterial patency (aptt > 70 deleterious) Enoxaparin better than UFH, with more noncerebral bleeding but higher net benefit SK: Fondaparinux better than UFH/Placebo in preventing re-mi and death with no excess of bleeding P< %% Death or re-mi EXTRACT-TIMI 25 (UFH vs Enox in pts; fibrin-specific TL) 9.8%% UFH 0.60% P< % Major bleeding (No ICH) P<0.04 ICH ENOX 0.6% 0.9% 12.7% OASIS 6 (TL Sub study; N=5436) P< % Net Benefit (all deaths, MI, major bleeding) Death and Re-MI in TL pts

17 Adjunctive therapy to lysis Recommendations

18 Antithrombotics Agents and doses

19 Thrombolysis SUMMARY Thrombolysis is an effective therapy indicated, in the absence of contraindications, when Primary-PCI cannot be performed. It should be given very soon, preferably in the pre-hospital setting and with fibrinspecific agents Successful TL is not a final treatment and should be complemented in all patients with early angiography (3-24 h) and intervention if indicated. All TL pts should be transfer immediately to a PCI-centre (ST-based rescue PCI?). Dual antiplatelet therapy (aspirin + clopidogrel) and parenteral anticoagulation are recommended in all TL patients. UFH or preferibly Enoxaparin should be used with fibrin-specific agents, whereas Fondaparinux should be considered with SK

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