TITLE: Dual Antiplatelet Therapy and Enoxaparin or Unfractionated Heparin for patients with ST-elevation Myocardial Infarction: A Review of the Clinical Evidence DATE: 29 August 2012 CONTEXT AND POLICY ISSUES Acute myocardial infarction (AMI) is one of the most frequent causes of mortality world-wide. 1 AMI is caused by prolonged ischemia resulting from sudden occlusion of a coronary artery due to thrombus formation. 1 ST-segment elevation myocardial infarction (STEMI) is a type of AMI. In STEMI patients ST-segment elevation is observed in the electrocardiogram. Prompt diagnosis of STEMI is important as the benefits of therapy are greater when initiated early. The initial reperfusion generally involves two options: pharmacologic reperfusion by fibrinolysis or mechanical reperfusion by primary percutaneous coronary intervention (PCI). 2 PCI is the preferred choice, if it can be performed in a timely fashion by experienced health care providers. 3 Not all hospitals, however, have PCI facilities and such facilities are generally fewer in rural areas compared to urban areas. 3 The reperfusion therapy used depends on the availability of resources and local practice patterns. 2 STEMI patients are treated with a variety of pharmacologic agents which include thrombolytic agents such as streptokinase and tenecteplase; anticoagulants such as unfractionated heparin and enoxaparin; and anti-platelets such as aspirin and clopidogrel. 4 The aim of this report is to review the clinical effectiveness of dual antiplatelet therapy combined with enoxaparin or unfractionated heparin compared with thrombolytic therapy in patients with STEMI. RESEARCH QUESTION What is the comparative clinical effectiveness of dual antiplatelet therapy combined with enoxaparin or unfractionated heparin versus thrombolytic therapy in patients with ST-elevation myocardial infarction? Disclaimer: The Rapid Response Service is an information service for those involved in planning and providing health care in Canada. Rapid responses are based on a limited literature search and are not comprehensive, systematic reviews. The intent is to provide a list of sources and a summary of the best evidence on the topic that CADTH could identify using all reasonable efforts within the time allowed. Rapid responses should be considered along with other types of information and health care considerations. The information included in this response is not intended to replace professional medical advice, nor should it be construed as a recommendation for or against the use of a particular health technology. Readers are also cautioned that a lack of good quality evidence does not necessarily mean a lack of effectiveness particularly in the case of new and emerging health technologies, for which little information can be found, but which may in future prove to be effective. While CADTH has taken care in the preparation of the report to ensure that its contents are accurate, complete and up to date, CADTH does not make any guarantee to that effect. CADTH is not liable for any loss or damages resulting from use of the information in the report. Copyright: This report contains CADTH copyright material. It may be copied and used for non-commercial purposes, provided that attribution is given to CADTH. Links: This report may contain links to other information available on the websites of third parties on the Internet. CADTH does not have control over the content of such sites. Use of third party sites is governed by the owners own terms and conditions.
KEY MESSAGE No relevant studies were identified that compared the clinical effectiveness of dual antiplatelet therapy combined with enoxaparin or unfractionated heparin versus thrombolytic therapy in patients with ST-elevation myocardial infarction. METHODS: Literature Search Strategy A limited literature search was conducted on key resources including MEDLINE, PubMed, The Cochrane Library (2012, Issue 8), University of York Centre for Reviews and Dissemination (CRD) databases, Canadian and major international health technology agencies, as well as a focused Internet search. No filters were applied to limit the retrieval by study type. Where possible, retrieval was limited to the human population. The search was also limited to English language documents published between January 01, 1998 and August 15, 2012. Selection Criteria and Methods Table 1: Selection Criteria Population Intervention Comparator Outcomes Study Designs Adult patients with ST segment elevation myocardial infarction Dual antiplatelet therapy (clopidogrel and ASA) combined with enoxaparin or unfractionated heparin Thrombolytic therapy (streptokinase, urokinase, alteplase, reteplase, tenecteplase) Reduction in thromboembolic events, morbidity/mortality, congestive heart failure, bleeding risk, cardiac adverse events, other adverse events Health technology assessments, systematic reviews and metaanalyses, randomized controlled trials (RCT), and non-randomized studies Exclusion Criteria Studies were excluded if they did not satisfy the selection criteria in Table 1; if they were published prior to1998, duplicate publications of the same study, or included in a selected health technology assessment or systematic review and did not provide additional relevant information. Critical Appraisal of Individual Studies No critical appraisal was conducted as no relevant studies were identified. Dual antiplatelet therapy and enoxaparin or UFH for STEMI 2
SUMMARY OF EVIDENCE: Quantity of Research Available The literature search yielded 248 citations. Upon screening titles and abstracts, 242 articles were excluded and six potentially relevant articles were selected for full-text review. However, upon further investigation none of the six articles satisfied the inclusion criteria and were excluded. No relevant studies were identified from the grey literature. No relevant health technology assessments, systematic reviews, randomized controlled trials or non-randomized studies were identified. Details of the study selection process are outlined in Appendix 1. References, which did not satisfy the selection criteria and included information regarding the intervention in STEMI patients, may be of interest and are provided in the Appendix 2. Summary of Study Characteristics Summary of Critical Appraisal Summary of Findings Limitations CONCLUSIONS AND IMPLICATIONS FOR DECISION OR POLICY MAKING: PREPARED BY: Canadian Agency for Drugs and Technologies in Health Tel: 1-866-898-8439 www.cadth.ca Dual antiplatelet therapy and enoxaparin or UFH for STEMI 3
REFERENCES 1. Wakai AP. Myocardial infarction (ST-elevation). Clin Evid (Online). 2011. 2. Diercks DB, Kontos MC, Weber JE, Amsterdam EA. Management of ST-segment elevation myocardial infarction in EDs. Am J Emerg Med. 2008 Jan;26(1):91-100. 3. Larson DM, Duval S, Sharkey SW, Garberich RF, Madison JD, Stokman PJ, et al. Safety and efficacy of a pharmaco-invasive reperfusion strategy in rural ST-elevation myocardial infarction patients with expected delays due to long-distance transfers. Eur Heart J. 2012 May;33(10):1232-40. 4. Lincoff AM, Cutlip D. Anticoagulant therapy in acute ST elevation myocardial infarction. 2012 [cited 2012 Aug 23]. In: UpToDate [Internet]. 20.8. Waltham (MA): UpToDate; 1992 - Available from: www.uptodate.com Subscription required. Dual antiplatelet therapy and enoxaparin or UFH for STEMI 4
APPENDIX 1: Selection of Included Studies 248 citations identified from electronic literature search and screened 242 citations excluded 6 potentially relevant articles retrieved for scrutiny (full text, if available) No potentially relevant reports retrieved from other sources (grey literature) 6 potentially relevant reports 6 reports excluded: -irrelevant comparator (2) -irrelevant condition (2) -other (review articles, editorials) (2) No relevant reports Dual antiplatelet therapy and enoxaparin or UFH for STEMI 5
APPENDIX 2: References of Potential Interest (Comparison not Relevant) Larson DM, Duval S, Sharkey SW, Garberich RF, Madison JD, Stokman PJ, et al. Safety andefficacy of a pharmaco-invasive reperfusion strategy in rural ST-elevation myocardial infarction patients with expected delays due to long-distance transfers. Eur Heart J. 2012 May;33(10):1232-40. Yoo SY, Shin DH, Lee JY, Cheong S, Jang JK, Lee C. Clinical outcomes of brief versusprolonged unfractionated heparin infusion after primary percutaneous coronary intervention for ST-segment elevation myocardial infarction in the drug-eluting stent era: realworld, single-centre experience. Acta Cardiol. 2011 Aug;66(4):439-45. Heestermans T, Suryapranata H, ten Berg JM, Mosterd A, Gosselink AT, Kochman W, et al. Facilitated reperfusion with prehospital glycoprotein IIb/IIIa inhibition: predictors of complete STsegment resolution before primary percutaneous coronary intervention in the On-TIME 2 trial: correlates of reperfusion before primary PCI. J Electrocardiol. 2011 Jan;44(1):42-8. Armstrong PW, Gershlick A, Goldstein P, Wilcox R, Danays T, Bluhmki E, et al. The Strategic Reperfusion Early After Myocardial Infarction (STREAM) study. Am Heart J. 2010 Jul;160(1):30-5. Buller CE, Pate GE, Armstrong PW, O'Neill BJ, Webb JG, Gallo R, et al. Catheter thrombosis during primary percutaneous coronary intervention for acute ST elevation myocardial infarction despite subcutaneous low-molecular-weight heparin, acetylsalicylic acid, clopidogrel and abciximab pretreatment. Can J Cardiol [Internet]. 2006 May 1 [cited 2012 Aug 23];22(6):511-5. Available from: http://www.ncbi.nlm.nih.gov/pmc/articles/pmc2560555 Dual antiplatelet therapy and enoxaparin or UFH for STEMI 6