Pretreatment of patients with ST-segment elevation myocardial infarction with heparin: a systematic review and meta-analysis

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Skip to main content Home About Submit ALERTS / RSS Search for this keyword Advanced Search Pretreatment of patients with ST-segment elevation myocardial infarction with heparin: a systematic review and meta-analysis View ORCID Profile Gonçalo Costa , View ORCID Profile Bernardo Resende , View ORCID Profile Bárbara Oliveiros , Lino Gonçalves , Rogério Teixeira doi: https://doi.org/10.1101/2024.01.22.24301634 Gonçalo Costa 1 Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra , Coimbra, Portugal 2 Faculdade de Medicina da Universidade de Coimbra , Coimbra, Portugal MD, MSc Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Gonçalo Costa For correspondence: gnfcosta.93{at}gmail.com Bernardo Resende 1 Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra , Coimbra, Portugal MD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Bernardo Resende Bárbara Oliveiros 2 Faculdade de Medicina da Universidade de Coimbra , Coimbra, Portugal 3 Coimbra Institute for Clinical and Biomedical Research (iCBR) , Coimbra, Portugal PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site ORCID record for Bárbara Oliveiros Lino Gonçalves 1 Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra , Coimbra, Portugal 2 Faculdade de Medicina da Universidade de Coimbra , Coimbra, Portugal 3 Coimbra Institute for Clinical and Biomedical Research (iCBR) , Coimbra, Portugal MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Rogério Teixeira 1 Serviço de Cardiologia, Centro Hospitalar e Universitário de Coimbra , Coimbra, Portugal 2 Faculdade de Medicina da Universidade de Coimbra , Coimbra, Portugal 3 Coimbra Institute for Clinical and Biomedical Research (iCBR) , Coimbra, Portugal MD, PhD Find this author on Google Scholar Find this author on PubMed Search for this author on this site Abstract Full Text Info/History Metrics Data/Code Preview PDF ABSTRACT Background Unfractionated heparin (UFH) is frequently administered before percutaneous coronary intervention (PCI) in patients with ST-segment elevation myocardial infarction (STEMI). However, current guidelines do not provide clear recommendations for UFH pretreatment before arrival at the coronary catheterisation laboratory. Methods Between June and July 2023, we systematically searched PubMed, Embase and Cochrane databases for studies comparing UFH pretreatments in patients with STEMI. A random-effects meta-analysis and meta-regression analyses were performed. Results Fourteen studies were included, of which four were randomised clinical trials (RCTs). A total of 76446 patients were included: 31238 in the pretreatment group and 39208 in the control group. Our meta-analysis revealed a lower all-cause mortality for the pretreatment strategy when compared with the control group, albeit with high heterogeneity (pooled odds ratio (OR) = 0.61, 95% confidence interval (CI) [0.49 - 0.76], P < 0.01; I² = 77%); lower in-hospital cardiogenic shock (pooled OR = 0.68, 95% CI [0.58, 0.78], P < 0.21; I² = 27%) and a higher rate of spontaneous reperfusion events (pooled OR = 1.68, 95% CI [1.47, 1.91], P < 0.01; I² = 79%). In terms of major bleeding, the UFH pretreatment strategy further revealed a decreased rate of events (pooled OR = 0.85, 95% CI [0.73, 0.99], P = 0.40; I² = 4%). Conclusions Our study suggests that UFH pretreatment in patients with STEMI undergoing primary PCI was associated to reduced all-cause mortality, cardiogenic shock, enhancing reperfusion rates, whilst diminishing major bleeding events. INTRODUCTION Acute ST-elevation myocardial infarction (STEMI) is a life-threatening condition that requires prompt reperfusion therapy to minimise myocardial damage and improve patient outcomes. Percutaneous coronary intervention (PCI) is widely recognised as the gold standard treatment for patient with STEMI as it helps restore coronary blood flow and salvage ischaemic myocardium ( 1 ). However, the optimal antithrombotic strategy for the pretreatment of patients with STEMI undergoing PCI remains a topic of debate. One common approach is heparin administration prior to patient arrival at the coronary catheterisation laboratory. Heparin, specifically unfractionated heparin (UFH), has been previously used in clinical practice to improve spontaneous reperfusion rates and reduce the clot burden ( 2 ). Improved coronary blood flow prior to PCI, which positively impacts patient outcomes, has been previously demonstrated ( 3 ). UFH is a rapidly acting anticoagulant with a short half-life of approximately 1–2 hours after intravenous administration ( 4 ). Its pharmacokinetic profile, coupled with antidote availability, means that UFH is a potential early-administration candidate in patients with STEMI. Despite the widespread use of UFH during PCI, robust evidence is scarce on the benefits of administering anticoagulation at earlier stages within a PCI context. To date, only four small randomised controlled trials (RCTs) ( 2 , 5 – 7 ) and several observational studies ( 8 – 17 ) with varying results on patient-relevant outcomes have investigated UFH pretreatment in patients with STEMI undergoing PCI. Additionally, the evidence on mortality outcomes remains inconclusive. Consequently, recent European guidelines on acute coronary syndromes have endorsed UFH during PCI but they do not provide clear recommendations for UFH pretreatment before arrival at the coronary catheterisation laboratory ( 1 ). Therefore, we conducted a systematic review and meta-analysis to evaluate efficacy and safety outcomes associated with UFH pretreatment in patients with STEMI undergoing primary PCI. METHODS Protocol and Registration This study was designed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement ( Supplementary Table 1 ). This systematic review and meta-analysis were registered with the PROSPERO database (CRD42023422529). In total, we made two changes to the original registry. Firstly, we expanded the scope of secondary outcomes to encompass stroke and major adverse cardiovascular outcomes. Additionally, we excluded post-PCI Thrombolysis in Myocardial Infarction (TIMI) flow-grade and no-reflow phenomena due to insufficient data. Secondly, we substituted the control arm, replacing UFH administration at the catheterisation laboratory with either no UFH pretreatment or delayed administration. This alteration mitigated a potential major limitation in study selection. Literature Searches We systematically checked the Cochrane Controlled Register of Trials (CENTRAL), EMBASE and PubMed between June and July 2023. In all databases, we accessed both interventional and observational studies which compared heparin pretreatment with delayed heparin administration in patients with STEMI in multiple combinations. Our selection criteria had no language or date restrictions. We also analysed bibliographic references in eligible studies to capture additional articles via cross referencing. The meta-analysis search and selection strategy is shown ( Figure 1 ). Download figure Open in new tab Figure 1. Literature search flow diagram. Eligibility Criteria We used the following criteria to define study eligibility: 1) studies comparing the use of UFH pretreatment, prior to arrival at the catheterisation laboratory, with either no UFH pretreatment or delayed administration and 2) studies describing UFH administration timing and doses. We excluded studies reporting the use of other anticoagulant types as pretreatments that did not encompass full-text article publications and without control groups. Primary and Secondary Outcomes Primary outcomes were all-cause mortality and major bleeding events. Secondary endpoints were in-hospital cardiogenic shock, spontaneous reperfusion (defined as pre-PCI TIMI flow 2–3), stroke, cardiovascular mortality, major adverse cardiovascular outcomes, minor bleeding events and all bleeding events. Data Collection and Management Two authors systematically reviewed titles and abstracts of retrieved publications to identify studies meeting inclusion criteria. Any disagreements on study eligibility were resolved by consensus and discussion. Data collected from selected studies were subject to a narrative synthesis approach covering the study population, including key demographics and clinical characteristics, interventions, and outcomes. For studies with multiple sequential publications, measures were taken to avoid the duplication of results. When summary data were not readily available, calculations were performed using available study data. Risk of Bias and Certainty Assessments Two authors independently assessed the risk of bias in articles according to the Cochrane Collaboration’s “Risk of bias” tool for RCTs and the Newcastle–Ottawa Scale for observational studies. Studies with a high risk of bias were excluded. Quality evaluations for studies are presented in the “risk of bias summary” table ( Table 1 ) or in the Newcastle–Ottawa Scale summary table ( Table 2 ). Regarding certainty of evidence we used Grading of Recommendations, Assessment, Development and Evaluations framework. View this table: View inline View popup Download powerpoint Table 1. Risk of bias summary. Green circle – low risk of bias; Red circle – high circle of bias. View this table: View inline View popup Download powerpoint Table 2. Newcastle–Ottawa Scale summary. * - 1 point Statistical Analysis We conducted our meta-analysis to pool data across studies using a random effects model. The mean effect was considered significant if its 95% confidence interval (CI) did not include zero. Outcomes were addressed by estimating odds ratios (ORs). Statistical heterogeneity was evaluated by the visual inspection of forest plots, the I² statistical index ( 40% high heterogeneity) and Egger’s linear regression tests. The software package used for the meta-analysis was Review Manager (RevMan) version 5.4.1. Meta-regression was performed considering one independent variable each time to generate regression model assumptions, such as the absence of multicollinearity and at least 5–10 cases (case studies) per independent variable. Moreover, due to limited complete pairwise data, multiple meta-regression was not valid. We applied a random-effects model using DerSimonian–Laird and Knapp–Hartung standard error adjustment methods using meta-regression procedures in IBM SPSS, version 28. All data were evaluated at a 5% significance level (P<0.05). RESULTS Search Results Our literature search identified 628 relevant records. Following duplicate removal, 525 publications were excluded based on pre-defined inclusion and exclusion criteria. Finally, 14 studies, 4 RCTs ( 2 , 5 – 7 ) and 10 observational studies ( 8 – 17 ), were included ( Figure 1 ) with a total of 76446 patients: 31238 in the pretreatment group and 39208 in the control group. Most studies used UFH doses between 5000-10000 U or 90 U/kg. Two studies opted for a high dose of 300 U/kg in the intervention arm. The timing of pretreatment varied, often given during transport to a PCI-capable hospital. While most studies mention aspirin loading, the choice of P2Y12 inhibitors varied, with clopidogrel being the most common. Study characteristics of selected studies are presented in Table 3 and baseline patient characteristics are summarised in Table 4 . View this table: View inline View popup Download powerpoint Table 3. Characteristics of selected studies. ACT = Activated Clotting Time, CL = Catheterisation Laboratory, ER = Emergency Room, GpIIb/IIIa = Glycoprotein IIb/IIIa, IV = Intravenous, NR = Not Reported, PCI = Percutaneous Coronary Intervention, SC = Subcutaneous, UF = Unfractionated Heparin. View this table: View inline View popup Table 4. Patient demographics and baseline characteristics. NR = Not Reported, SD = Standard deviation Primary Outcomes Our meta-analysis identified lower all-cause mortality rates using a pretreatment strategy when compared with a control group, albeit with high heterogeneity (pooled OR = 0.61, 95% CI [0.49, 0.76], P < 0.01; I² = 77%). In subgroup analyses, in-hospital and 30-day mortality maintained statistical significance (pooled OR = 0.60, 95% CI [0.42, 0.86], P < 0.41; I² = 0%; pooled OR = 0.63, 95% CI [0.46, 0.86], P < 0.01; I² = 81%, respectively). A reduction in mortality effects was also observed for 1-year all-cause mortality, but with high heterogeneity (pooled OR = 0.56, 95% CI [0.32, 0.96], P < 0.01; I² = 91%) ( Figure 2 , Figure S1 ). In meta-regression analyses, age ratio (b = - 0.90; p = 0.786), aspirin ratio (b = -0.81; p = 0.378), PY12 inhibitor ratio (b = -0.49; p = 0.351), ticagrelor ratio (b = -0.06; p = 0.519) or ‘time to PCI’ (b = 0.18; p = 0.519) were not predictors of the evaluated effect size. However, the effect size tended to be greater when the clopidogrel ratio was smaller (b = -0.89; p = 0.026) ( Figure S2 ). Download figure Open in new tab Figure 2. Forest plot showing all-cause mortality comparing unfractionated heparin pretreatment versus delayed administration. M–H, Mantel–Haenszel. In terms of major bleeding, the pretreatment strategy further revealed a decreased rate of events (pooled OR = 0.85, 95% CI [0.73, 0.99], P = 0.40; I² = 4%) ( Figure 3 , Figure S3 ). Download figure Open in new tab Figure 3. Forest plot showing major bleeding events comparing unfractionated heparin pretreatment versus delayed administration. M–H, Mantel–Haenszel. Secondary Outcomes In terms of secondary outcomes, in-hospital cardiogenic shock was statistically significantly favourable for the pretreatment strategy (pooled OR = 0.68, 95% CI [0.58, 0.78], P < 0.21; I² = 27%) ( Figure 4 , Figure S4 ). Additionally, the pretreatment strategy exhibited a significantly higher rate of spontaneous reperfusion events (pooled OR = 1.68, 95% CI [1.47, 1.91], P < 0.01; I² = 79%) ( Figure 5 , Figure S5 ) and stroke (pooled OR = 0.94, 95% CI [0.66, 1.34], P = 0.98; I² = 0%). Cardiovascular mortality, major adverse cardiovascular events, minor bleeding and all-bleeding analyses were not performed due to insufficient data reported in the included studies. Download figure Open in new tab Figure 4. Forest plot showing in-hospital cardiogenic shock comparing unfractionated heparin pretreatment versus delayed administration. M–H, Mantel–Haenszel. Download figure Open in new tab Figure 5. Forest plot showing spontaneous reperfusion events (pre-percutaneous coronary intervention Thrombolysis in Myocardial Infarction flow 2–3) comparing unfractionated heparin pretreatment versus delayed administration. M–H, Mantel– Haensz Risk of Bias and Evidence Certainty Overall, selected studies demonstrated a low–moderate risk of bias. However, due to the nature of the intervention, a high risk of bias was observed in participant and personnel blinding ( Tables 3 and 4 ). Therefore, considering our results and the risk of bias in terms of our robust evidence, we considered low certainty for primary outcomes and very low for secondary outcomes ( Supplementary Table 2 ). DISCUSSION We performed a systematic review and meta-analysis on the efficacy and safety outcomes of UFH pretreatment in patients with STEMI undergoing primary PCI. We observed that UFH pretreatment was associated with a lower risk of all-cause mortality, in-hospital cardiogenic shock and spontaneous reperfusion events. Furthermore, an improvement in safety outcomes was observed for reduced major bleeding events between groups. Current guidelines recommend adjunctive antithrombotic treatment with antiplatelet and anticoagulant medication before primary PCI in patients diagnosed with STEMI, but ideal administration times remain controversial ( 1 ). The notable reduction in all-cause mortality associated with UFH pretreatment underscores its potential as a valuable intervention; enhanced coronary blood flow before primary PCI which mitigates myocardial damage is compelling. Previous studies have suggested that UFH, as a rapidly acting anticoagulant, may facilitate spontaneous reperfusion rates and reduce the clot burden ( 2 ). This mechanism is particularly relevant within the STEMI context, where rapid and effective reperfusion is a critical determinant of patient outcomes ( 3 ), as shown by favourable outcomes in in-hospital, 30-day and 1-year mortality in our analyses. These findings further support the potential use of UFH pretreatment during critical post-PCI phases and in reducing early mortality. By aligning the potential benefits of efficacy effects with safety considerations, the assessment of major bleeding events revealed a significant difference in the pretreatment group when compared with the control group. This observation did not exclude safety clinical evaluations before UFH pretreatment, especially given the delicate balance between preventing thrombotic events and avoiding bleeding complications ( 18 ). While acknowledging our results for this outcome, the caveat is that not enough data are available to support this conclusion when applied to elderly and frail patients. Beyond mortality and haemorrhagic events, a substantial reduction in in-hospital cardiogenic shock associated with UFH pretreatment has profound clinical implications. Cardiogenic shock is a pivotal determinant of patient prognosis post-STEMI ( 19 ). Previous studies have demonstrated associations between successful reperfusion and a reduced risk of cardiogenic shock ( 20 ), so any intervention that potentially mitigates its occurrence warrants careful consideration. The observed reduction in this high-risk complication suggests that UFH pretreatment may help improve haemodynamic stability during acute STEMI phases, thus potentially impacting the broader course of the disease. Moreover, our analyses identified a significant increase in spontaneous reperfusion event rates upon UFH pretreatment. Swift and effective reperfusion lies at the core of STEMI management ( 3 ), and this finding aligns with the mechanistic rationale underpinning UFH pretreatment. The potential for UFH to enhance the early restoration of coronary blood flow introduces an intriguing facet to the clinical benefits of the strategy. This prompts further exploration into the mechanisms underlying these outcomes, potentially involving thrombus burden reduction, and enhancing coronary flow. In light of recent research, the study by Emilsson et al. ( 12 ), a well-conducted and -powered study, provides a valuable addition to the UFH pretreatment debate in patients with STEMI. By analysing data from the Swedish Coronary Angiography and Angioplasty Registry, Emilsson’s research aligns with our findings. The identification of a significantly lower risk of 30-day mortality, major bleeding events and cardiogenic shock lends further credence to the potential benefits of UFH pretreatment in improving patient outcomes. Moreover, in two studies by Giralt et al ( 13 , 14 ), both having significant weight in our meta-analysis, the authors witnessed a sustained reduction in mortality outcomes, whether in-hospital, 30-day or 1-year mortality, and lower rates of in-hospital cardiogenic shock. However, both analyses showed similar grades of major bleeding events between groups despite a slight no-benefit-tendency in the pretreatment group. We observed that the mean door-to-balloon time in Emilson et al. was somewhat higher when compared with the studies by Giralt et al., which may explain these differences. Collectively, our systematic review and meta-analysis provide crucial insights into the potential benefits and limitations of UFH pretreatment in primary PCI for patients with STEMI. The reduction in all-cause mortality, coupled with improvements in in-hospital cardiogenic shock and spontaneous reperfusion rates, underscores the potential advantages of this strategy. Although the absence of significant differences in major bleeding and stroke suggests potential safety issues, further exploration is warranted. Rigorous, large-scale RCTs with standardised protocols and reported outcomes are pivotal in establishing definitive efficacy and safety evidence for UFH pretreatment. This evidence will not only guide clinical decision-making but also optimise outcomes in the dynamic STEMI management field. Study Limitations By acknowledging study strengths and limitations, some aspects of our research require careful consideration. Inherent heterogeneity across selected studies, stemming from variations in patient characteristics, UFH dosages and different concomitant antiplatelet regimens, may have introduced potential biases and limited the generalisability of our findings. A major difficulty in our study was different UFH administration timings in the pretreatment group, which limited the determination of exact administration times for anticoagulation and PCI treatments. Due to a lack of data in selected studies, we were unable to assess heparin drug-related problems such as heparin-induced thrombocytopenia or osteopenia ( 21 , 22 ). Due to the low incidence of these issues ( 23 ), we hypothesize that they exert a low impact on the choice of UFH as an anticoagulant therapy. Despite these challenges, we addressed these concerns by analysing a significative number of studies using strong statistical methods and robust subgroup analyses. The absence of comprehensive reporting for specific outcomes, such as cardiovascular mortality, major adverse cardiovascular events, minor bleeding, and all bleeding events, underscores the importance of standardised reporting in future research. CONCLUSION From our study, UFH pretreatment in patients with STEMI undergoing primary PCI has potential promise in reducing mortality, cardiogenic shock and enhancing reperfusion rates. High-scale RCTs are required to address these clinical questions in the future. Data Availability All included studies are publicaly available Author Contributions GC: Conceptualization, Data curation, Formal analysis, Methodology, Project administration, Writing – original draft; BR: Data curation, Formal analysis, Methodology, Writing – original draft; BO: Supervision, Formal analysis; LG: Supervision, Writing - review & editing; RT: conception and design, interpretation of data, revision of the manuscript, final approval and is responsible for the overall content as guarantor. Footnotes ↵ (a) Both authors share co-authorship E-mail addresses: Bernardo Resende: bernardoresende028{at}gmail.com Bárbara Oliveiros: boliveiros{at}fmed.uc.pt , Lino Gonçalves: lgoncalv{at}ci.uc.pt , Rogério Teixeira: rogeriopteixeira{at}gmail.com Funding The authors have no conflicts of interest to declare. ABREVIATIONS CENTRAL Cochrane Controlled Register of Trials CI confidence interval ORs odds ratios PCI percutaneous coronary intervention RCTs randomized clinical trials SCAAR Swedish Coronary Angiography and Angioplasty Registry STEMI ST-segment elevation myocardial infarction TIMI Thrombolysis in Myocardial Infarction UFH Unfractionated heparin REFERENCES 1. ↵ Byrne RA , Rossello X , Coughlan JJ , Barbato E , Berry C , Chieffo A , et al. 2023 ESC Guidelines for the management of acute coronary syndromes: Developed by the task force on the management of acute coronary syndromes of the European Society of Cardiology (ESC) . Eur Heart J . 2023 Aug; ehad191 . OpenUrl 2. ↵ Karlsson S , Andell P , Mohammad MA , Koul S , Olivecrona GK , James SK , et al. Editor’s Choice- Heparin pre-treatment in patients with ST-segment elevation myocardial infarction and the risk of intracoronary thrombus and total vessel occlusion. Insights from the TASTE trial. Eur Hear journal Acute Cardiovasc care [Internet] . 2019 Feb 1 [cited 2023 Jun 5 ]; 8 ( 1 ): 15–23 . Available from: https://pubmed.ncbi.nlm.nih.gov/28862032/ OpenUrl 3. ↵ Stone GW , Cox D , Garcia E , Brodie BR , Morice MC , Griffin J , et al. Normal flow (TIMI-3) before mechanical reperfusion therapy is an independent determinant of survival in acute myocardial infarction: analysis from the primary angioplasty in myocardial infarction trials . Circulation [Internet ]. 2001 Aug 7 [cited 2023 Jun 5 ]; 104 ( 6 ): 636–41 . Available from: https://pubmed.ncbi.nlm.nih.gov/11489767/ OpenUrl 4. ↵ Kandrotas RJ . Heparin pharmacokinetics and pharmacodynamics. Clin Pharmacokinet [Internet] . 1992 [cited 2023 Jun 5]; 22 ( 5 ): 359–74 . Available from: https://pubmed.ncbi.nlm.nih.gov/1505142/ OpenUrl 5. ↵ Braga JC , Esteves FP , Esteves JP , Latado AL , Godinho AG , Azevedo A , et al. Confirmation that heparin is an alternative means of promoting early reperfusion . Coron Artery Dis [Internet ]. 1998 [cited 2023 Jun 5 ]; 9 ( 6 ): 335–8 . Available from: https://pubmed.ncbi.nlm.nih.gov/9812183/ OpenUrl 6. Cantor WJ , Lavi S , Džavík V , Cairns J , Cheema AN , Della Siega A , et al. Upstream anticoagulation for patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention: Insights from the TOTAL trial . Catheter Cardiovasc Interv . 2020 ; 96 ( 3 ): 519 – 25 . OpenUrl 7. ↵ Fakhr-Mousavi A , Cheshmkhorooshan S , Vakilpour A , Mousavi SM . The effect of heparin administration time on thrombolysis in myocardial infarction flow grade in patients with acute ST-elevation myocardial infarction treated with primary percutaneous coronary intervention . ARYA Atheroscler [Internet ]. 2022 May 1 [cited 2023 Jun 5 ]; 18 ( 3 ): 1–7 . Available from: https://europepmc.org/articles/PMC9931947 OpenUrl 8. ↵ Ariza A , Ferreiro JL , Sánchez-Salado JC , Lorente V , Gómez-Hospital JA , Cequier Á . Early Anticoagulation May Improve Preprocedural Patency of the Infarct-related Artery in Primary Percutaneous Coronary Intervention. Rev Española Cardiol (English Ed. 2013 ; 66 ( 2 ): 148–50 . OpenUrl 9. Bloom JE , Andrew E , Nehme Z , Dinh DT , Fernando H , Shi WY , et al. Pre-hospital heparin use for ST-elevation myocardial infarction is safe and improves angiographic outcomes . Eur Hear Journal Acute Cardiovasc Care [Internet ]. 2021 Dec 18 [cited 2023 Jun 5 ]; 10 ( 10 ): 1140–7 . Available from: https://academic.oup.com/ehjacc/article/10/10/1140/6311429 OpenUrl 10. Chung WY , Han MJ , Cho YS , Kim K Il , Chang HJ , Youn TJ , et al. Effects of the early administration of heparin in patients with ST-elevation myocardial infarction treated by primary angioplasty . Circ J [Internet ]. 2007 [cited 2023 Jun 5 ]; 71 ( 6 ): 862–7 . Available from: https://pubmed.ncbi.nlm.nih.gov/17526981/ OpenUrl 11. d’Entremont MA , Laferrière C , Bérubé S , Couture ÉL , Lepage S , Huynh T , et al. The effect of ASA, ticagrelor, and heparin in ST-segment myocardial infarction patients with prolonged transport times to primary percutaneous intervention . Catheter Cardiovasc Interv [Internet ]. 2021 Mar 1 [cited 2023 Jun 5 ]; 97 ( 4 ): 591–9 . Available from: https://pubmed.ncbi.nlm.nih.gov/32860646/ OpenUrl 12. ↵ Emilsson OL , Bergman S , Mohammad MA , Olivecrona GK , Götberg M , Erlinge D , et al. Pretreatment with heparin in patients with ST-segment elevation myocardial infarction: a report from the Swedish Coronary Angiography and Angioplasty Registry (SCAAR) . EuroIntervention . 2022 Oct 1; 18 ( 9 ): 709 – 18 . OpenUrl 13. ↵ Giralt T , Carrillo X , Rodriguez-Leor O , Fernandez-Nofrerias E , Rueda F , Serra-Flores J , et al. Time-dependent effects of unfractionated heparin in patients with ST-elevation myocardial infarction transferred for primary angioplasty . Int J Cardiol [Internet ]. 2015 Aug 28 [cited 2023 Jun 5 ]; 198 : 70–4 . Available from: https://pubmed.ncbi.nlm.nih.gov/26159240/ OpenUrl 14. ↵ Giralt T , Ribas N , Freixa X , Sabaté M , Caldentey G , Tizón-Marcos H , et al. Impact of pre-angioplasty antithrombotic therapy administration on coronary reperfusion in ST-segment elevation myocardial infarction: Does time matter? Int J Cardiol . 2021 ; 325 : 9 – 15 . OpenUrl 15. Mcginley C , Mordi IR , Kell P , Currie P , Hutcheon S , Koch S , et al. Prehospital Administration of Unfractionated Heparin in ST-Segment Elevation Myocardial Infarction Is Associated With Improved Long-Term Survival . J Cardiovasc Pharmacol . 2020 ; 76 ( 2 ): 159 – 63 . OpenUrl 16. Verheugt FWA , Liem A , Zijlstra F , Marsh RC , Veen G , Bronzwaer JGF . High dose bolus heparin as initial therapy before primary angioplasty for acute myocardial infarction: Results of the heparin in early patency (HEAP) pilot study . J Am Coll Cardiol . 1998 ; 31 ( 2 ): 289 – 93 . OpenUrl FREE Full Text 17. ↵ Żurowska-Wolak M , Owsiak M , Bartuś S , Mikos M . The influence of pre-hospital medication administration in ST-elevation myocardial infarction patients on left ventricular ejection fraction and intra-hospital death . Postep w Kardiol Interwencyjnej . 2021 ; 17 ( 1 ): 39 – 45 . OpenUrl 18. ↵ Zidane M , Schram MT , Planken EW , Molendijk WH , Rosendaal FR , Van Der Meer FJM , et al. Frequency of major hemorrhage in patients treated with unfractionated intravenous heparin for deep venous thrombosis or pulmonary embolism: A study in routine clinical practice . Arch Intern Med . 2000 ; 160 ( 15 ): 2369 – 73 . OpenUrl CrossRef PubMed Web of Science 19. ↵ Dalzell JR . Review of Cardiogenic Shock After Acute Myocardial Infarction . Jama . 2022 ; 327 ( 9 ): 878 . OpenUrl 20. ↵ Zeymer U , Huber K, fu Y, Ross A, Granger C, Goldstein P , et al. Impact of TIMI 3 patency before primary percutaneous coronary intervention for ST-elevation myocardial infarction on clinical outcome: Results from the ASSENT-4 PCI study. Eur Hear J Acute Cardiovasc Care . 2012 ; 1 ( 2 ): 136–42 . OpenUrl 21. Bussey H , Francis JL . Heparin overview and issues . Pharmacotherapy . 2004 ; 24 ( 8 II). 22. ↵ Niccolai CS , Hicks RW , Oertel L , Francis JL . Unfractionated heparin: Focus on a high-alert drug . Pharmacotherapy . 2004 ; 24 ( 8 II). 23. ↵ Hogan M , Berger JS . Heparin-induced thrombocytopenia (HIT): Review of incidence, diagnosis, and management . Vasc Med (United Kingdom ). 2020 ; 25 ( 2 ): 160 – 73 . OpenUrl View the discussion thread. Back to top Previous Next Posted January 25, 2024. Download PDF Data/Code Email Thank you for your interest in spreading the word about medRxiv. NOTE: Your email address is requested solely to identify you as the sender of this article. 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Share Pretreatment of patients with ST-segment elevation myocardial infarction with heparin: a systematic review and meta-analysis Gonçalo Costa , Bernardo Resende , Bárbara Oliveiros , Lino Gonçalves , Rogério Teixeira medRxiv 2024.01.22.24301634; doi: https://doi.org/10.1101/2024.01.22.24301634 Share This Article: Copy Citation Tools Pretreatment of patients with ST-segment elevation myocardial infarction with heparin: a systematic review and meta-analysis Gonçalo Costa , Bernardo Resende , Bárbara Oliveiros , Lino Gonçalves , Rogério Teixeira medRxiv 2024.01.22.24301634; doi: https://doi.org/10.1101/2024.01.22.24301634 Citation Manager Formats BibTeX Bookends EasyBib EndNote (tagged) EndNote 8 (xml) Medlars Mendeley Papers RefWorks Tagged Ref Manager RIS Zotero Tweet Widget Facebook Like Google Plus One Subject Area Cardiovascular Medicine Subject Areas All Articles Addiction Medicine (574) Allergy and Immunology (865) Anesthesia (304) Cardiovascular Medicine (4462) Dentistry and Oral Medicine (445) Dermatology (383) Emergency Medicine (611) Endocrinology (including Diabetes Mellitus and Metabolic Disease) (1517) Epidemiology (15251) Forensic Medicine (31) Gastroenterology (1132) Genetic and Genomic Medicine (6621) Geriatric Medicine (669) Health Economics (1002) Health Informatics (4564) Health Policy (1372) Health Systems and Quality Improvement (1617) Hematology (544) HIV/AIDS (1272) Infectious Diseases (except HIV/AIDS) (15938) Intensive Care and Critical Care Medicine (1107) Medical Education (624) Medical Ethics (147) Nephrology (670) Neurology (6643) Nursing (346) Nutrition (1001) Obstetrics and Gynecology (1149) Occupational and Environmental Health (957) Oncology (3350) Ophthalmology (981) Orthopedics (369) Otolaryngology (421) Pain Medicine (436) Palliative Medicine (130) Pathology (665) Pediatrics (1698) Pharmacology and Therapeutics (694) Primary Care Research (714) Psychiatry and Clinical Psychology (5465) Public and Global Health (9259) Radiology and Imaging (2212) Rehabilitation Medicine and Physical Therapy (1372) Respiratory Medicine (1198) Rheumatology (598) Sexual and Reproductive Health (716) Sports Medicine (533) Surgery (715) Toxicology (100) Transplantation (289) Urology (265) (function(){function c(){var b=a.contentDocument||a.contentWindow.document;if(b){var d=b.createElement('script');d.innerHTML="window.__CF$cv$params={r:'a03d613c2bd658f4',t:'MTc4MDE0MDM0Mw=='};var a=document.createElement('script');a.src='/cdn-cgi/challenge-platform/scripts/jsd/main.js';document.getElementsByTagName('head')[0].appendChild(a);";b.getElementsByTagName('head')[0].appendChild(d)}}if(document.body){var a=document.createElement('iframe');a.height=1;a.width=1;a.style.position='absolute';a.style.top=0;a.style.left=0;a.style.border='none';a.style.visibility='hidden';document.body.appendChild(a);if('loading'!==document.readyState)c();else if(window.addEventListener)document.addEventListener('DOMContentLoaded',c);else{var e=document.onreadystatechange||function(){};document.onreadystatechange=function(b){e(b);'loading'!==document.readyState&&(document.onreadystatechange=e,c())}}}})();