Pre-hospital thrombolysis is associated with mortality reduction and prognosis improvement in patients with ST-elevation myocardial infarction Class n.7

Introduction Acute Myocardial Infarction (AMI) Acute myocardial infarction (AMI) is the most serious manifestation of cardiovascular diseases It is defined as the destruction of myocardial tissue resulting from insufficient supply of oxygen to the heart muscle 2 LCA – left coronary artery; RCA – right coronary artery; 1 – Occlusion; 2 – Myocardial infarction. 1.

The atherosclerosis is responsible for the majority of myocardial infarction. There is formation of thrombi in coronary arteries Atherosclerosis and trombi formation

Diagnosis Symptoms and alert ECG alterations (ST-elevation) 4

Identifying AMI signals (retrosternal discomfort or dyspnea, for example) with subsequent activation of the emergency number is the first step towards a speedy and effective action leading to a reduction of injuries and consequent harm to the patient. Symptoms and alert ?v=22bDs8teiZA&feature=relate d 5

ECG An electrocardiogram is a noninvasive transthoracic graphic produced by an electrocardiograph, which records the electrical activity of the heart over time. The typical ST segment duration is usually around 0.08 sec (80 ms). An elevation of >1mm and longer than 80 milliseconds may indicate myocardial infarction. ECG showing ST-segment elevation (orange) and reciprocal changes (blue) in the inferior leads

Treatment In acute myocardial infarction with ST-segment elevation the best treatment is reperfusion in the first 2 hours after the onset of symptoms. Reperfusion Pharmacological Thrombolytic Therapy Mechanical Angioplasty 4. ACC/AHA Guidelines for the management of patients with ST- elevation myocardial infarction. 5. JAMA, 287(15): 1943–

Study Aims and Question PHT Develop a study that could lead us to an answer to the question: Is PHT beneficial in terms of morbidity and mortality on patients with ST-elevation myocardial infarction? 8

Objectives Determine if pre-hospital thrombolysis is associated with reduction in early and late (1 year) cardiovascular mortality in patients with ST elevation myocardial infarction. Evaluate if pre-hospital trombolysis is associated with prognosis improvement such as: hospital stay, left ventricular ejection fraction, reenfartion rates, reenfartion readmission rates. Determine if pre-hospital thrombolysis performed by non medical teams is associated with and increase in complication rates. 9

Methods Search at Medline, ISI Web of Knowledge and Scopus using a predefined Query and select the ones that are related to our objective (the chosen articles are according the inclusion and exclusion criteria). In order to advance for Systematic review of prospective cohort studies and posterior metanalysis. 10

Query Database: Medline, ISI Web of Knowledge and Scopus (Thrombolysis OR Fibrinolytic Agents OR Thrombolytic Therapy) AND ("Acute Myocardial Infarction" OR Myocardial Infarction OR "ST-Elevation Myocardial Infarction") AND ("Pre-hospital" OR "Early" OR “Prehospital”) AND (“Treatment Delay OR “Delay” OR 1-year Outcome OR One Year Outcome) 11

Inclusion and exclusion criteria Inclusion: - Follow-ups till 1 year; - Study type: Clinical trials and Cohort studies only; -With ST-elevation; - PHT treatment with trombolytics; - Comparison between pre-hospital and in- hospital treatment. Exclusion: -Study language: Non-english studies; -Thrombolytic type: 1st generation thrombolytics; - Comparison between AMI and trombolytic treatment inexistent; - Studies that compare PHT with factors beyond our interest; - Studies with no abstract. 12

Flowchart 13

Article Selection ISI Web ok Knowledge 417 read 9 selected Medline 464 read 11 selected Scoppus 962 read 2 selected 14

Example 15

Prehospital thrombolysis in a rural community: short- and long-term survival. McAleer B, Ruane B, Burke E, Cathcart M, Costello A, Dalton G, Williams JR, Varma MP. Cardiac Unit, Erne Hospital, Enniskillen, Northern Ireland. In order to assess the feasibility and outcome of using prehospital thrombolysis in acute myocardial infarction in a rural community, we performed an open randomized study of patients with symptoms of acute myocardial infarction of less than 6 hours. One hundred and forty-five patients with acute myocardial infarction were allocated to receive IV streptokinase prehospital by means of a mobile coronary care unit (MCCU) (n = 43) or to receive IV streptokinase in hospital (n = 102). The mean delay time to treatment was 138 minutes (MCCU group) and 172 minutes (hospital group) (p less than 0.02). Reperfusion time was 88 minutes for the MCCU group and 92 minutes for the hospital group. Mortality at 14 days was 2.3% for the MCCU group and 11.7% for the hospital group (p less than 0.05). Six month mortality was 4.9% for the MCCU group and 17.3% for the hospital group (p = 0.03). Mortality at 1 year was 6.1% for the MCCU group and 20.0% for the hospital group (p = 0.04). There were no significant adverse events in either treatment group. Thus, prehospital thrombolysis by streptokinase is feasible and allows significant reduction in the delay time to treatment initiation. There are encouraging improvements in both short- and long-term survival with no apparent reduction in safety profile. PMID: [PubMed - indexed for MEDLINE] 16

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References 1.Drew Evan Fenton et al. Myocardial Infarction [Internet]. New York: eMedicine Clinical Knowledge Base; [updated Oct 10, 2008]. Available from: 2.Dean Jenkins, Stephen Gerred. ECG Library [internet] [updated Oct 12, 2002]. Available from: heart-attacks/ 3.Dean Jenkins, Stephen Gerred. ECG Library [internet] [updated Oct 12, 2002]. Available from 4.American College of Cardiology (ACC) and American Heart Association (AHA) (2004). ACC/AHA Guidelines for the management of patients with ST-elevation myocardial infarction. Report of the ACC/AHA Task Force on Practice Guidelines. 5.Aversano T, et al. Thrombolytic therapy vs. primary percutaneous coronary intervention for myocardial infarction in patients presenting to hospitals without on-site cardiac surgery. JAMA 2002 April 7; 287(15): 1943–

References 19 6.Erik Björklund, Ulf Stenestrand, Johan Lindbäck, et al. Pre-hospital thrombolysis delivered by paramedics is associated with reduced time delay and mortality in ambulance-transported real-life patients with ST-elevation myocardial infarction. European Heart Journal 2006 May; 27(10): Danchin N, Blanchard D, Steg PG, et al. Impact of pre-hospital thrombolysis for acute myocardial infarction on 1-year outcome: results from the French Nationwide USIC 2000 Registry. Circulation 2004 Oct 5;110(14): Danchin N, Durand E, Blanchard D. Pre-hospital thrombolysis in perspective. Overview of current guidelines and data from trials and registries on the best perfusion approach for acute MI with ST-elevation. European Heart Journal 2008 Oct 23. [Epub ahead of print] 9.S Goodacre, A-M Kelly, D Kerr. Potential impact of interventions to reduce times to thrombolysis. Emergency Medicine Journal 2004 Sep;21(5): J Wilkinson, K Foo, N Sekhri, J Cooper, et al. Interaction between arrival time and thrombolytic treatment in determining early outcome of acute myocardial infarction. Heart 2002 Dec;88(6):583-6.

References 20 9.S Goodacre, A-M Kelly, D Kerr. Potential impact of interventions to reduce times to thrombolysis. Emergency Medicine Journal 2004 Sep;21(5): J Wilkinson, K Foo, N Sekhri, J Cooper, et al. Interaction between arrival time and thrombolytic treatment in determining early outcome of acute myocardial infarction. Heart 2002 Dec;88(6):583-6.