title: Unfractionated heparin-clopidogrel combination in ST-elevation myocardial infarction not receiving reperfusion therapy.
abstract: OBJECTIVE
  We sought explore the relative benefits of unfractionated heparin (UFH) compared with enoxaparin, alone or in combination with clopidogrel, in ST-segment elevation myocardial infarction (STEMI) patients not undergoing reperfusion therapy.
  
  
  METHODS
  This is a propensity score study from The International Survey on Acute Coronary Syndromes in Transition Countries (ISACS-TC/NCT01218776) on patients admitted between October 2010-June 2013. There were a total of 1175 STEMI patients who did not receive mechanical or pharmacological reperfusion. Of these, 1063 were eligible for the aim of the study, being treated with UFH (522/1175; 44.4%) or enoxaparin (541/1175; 46%). Clopidogrel in combination with UFH or enoxaparin was given to 751 (63.9%) patients. The primary endpoint was in-hospital mortality. Secondary endpoints were intracranial hemorrhages, and clinically relevant bleedings.
  
  
  RESULTS
  After adjustment for any confounders, UFH was associated with a lower risk of in-hospital mortality in clopidogrel users (multivariate adjusted regression analysis: odds ratio [OR]: 0.62, 95% Confidence Interval [CI] 0.41-0.94) as compared with clopidogrel non-users (OR: 0.94, 95% CI 0.55-1.60). The observed effect was not associated with combined enoxaparin and clopidogrel therapy. Major bleeding events were comparable in the enoxaparin group and UFH group (0.4% and 1.5% respectively, p = 0.06). The risk of major hemorrhage was nearly similar with combined UFH-clopidogrel therapy (1.4%) as compared with UFH alone (1.9%), p = 0.67.
  
  
  CONCLUSIONS
  UFH - Clopidogrel combination was associated with a large mortality reduction in STEMI patients not undergoing reperfusion therapy and did not significantly increase the risk of major bleeding.
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy. Electronic address: raffaele.bugiardini@unibo.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Bugiardini
authors.affiliation: Department of Cardiology and Internal Medicine, Floreasca Emergency Hospital, Bucharest, Romania.
authors.forename: Maria
authors.initials: M
authors.lastname: Dorobantu
authors.affiliation: Clinical Center of Serbia, University of Belgrade, Serbia.
authors.forename: Zorana
authors.initials: Z
authors.lastname: Vasiljevic
authors.affiliation: University Clinic of Cardiology, University "Ss. Cyril and Methodius", Skopje, Macedonia.
authors.forename: Sasko
authors.initials: S
authors.lastname: Kedev
authors.affiliation: Clinical Center of Montenegro, Center of Cardiology, Podgorica, Montenegro.
authors.forename: Božidarka
authors.initials: B
authors.lastname: Knežević
authors.affiliation: Department for Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb, Croatia.
authors.forename: Davor
authors.initials: D
authors.lastname: Miličić
authors.affiliation: Department of Cardiology and Internal Medicine, Floreasca Emergency Hospital, Bucharest, Romania.
authors.forename: Lucian
authors.initials: L
authors.lastname: Calmac
authors.affiliation: Clinical Center of Banja Luka, Republika Srpska, Bosnia and Herzegovina.
authors.forename: Dijana
authors.initials: D
authors.lastname: Trninic
authors.affiliation: Department of Cardiology, University Clinical Centre of Kosovo, Prishtina, Kosovo.
authors.forename: Irfan
authors.initials: I
authors.lastname: Daullxhiu
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy.
authors.forename: Edina
authors.initials: E
authors.lastname: Cenko
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy.
authors.forename: Beatrice
authors.initials: B
authors.lastname: Ricci
authors.affiliation: Department of Cardiovascular, Respiratory, Nephrological, Anesthesiological and Geriatric Sciences, Sapienza University of Rome, Rome, Italy.
authors.forename: Paolo Emilio
authors.initials: PE
authors.lastname: Puddu
authors.affiliation: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Italy.
authors.forename: Olivia
authors.initials: O
authors.lastname: Manfrini
authors.affiliation: Institute of Natural Sciences, University of Physical Education, Budapest H-1123, Hungary; Department of Physiology, New York Medical College, Valhalla, NY 10595, USA.
authors.forename: Akos
authors.initials: A
authors.lastname: Koller
authors.affiliation: Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, CiberObn-Institute Carlos III, Autonomous University of Barcelona, Spain.
authors.forename: Lina
authors.initials: L
authors.lastname: Badimon
mesh_terms: D000368:Aged; D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D000077144:Clopidogrel; D004359:Drug Therapy, Combination; D017984:Enoxaparin / Q000009:adverse effects / Q000627:therapeutic use*; D005060:Europe; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D019538:Health Care Surveys; D006493:Heparin / Q000009:adverse effects / Q000627:therapeutic use*; D017052:Hospital Mortality; D006801:Humans; D020300:Intracranial Hemorrhages / Q000139:chemically induced; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009203:Myocardial Infarction / Q000175:diagnosis / Q000188:drug therapy* / Q000401:mortality; D016017:Odds Ratio; D010975:Platelet Aggregation Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D057216:Propensity Score; D012042:Registries; D012307:Risk Factors; D013988:Ticlopidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D006493:Heparin; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: Clopidogrel; Enoxaparin; No-reperfusion therapy; Outcomes; ST-segment elevation myocardial infarction; Unfractionated heparin