American Journal of Emergency Medicine 31 (2013) 750-751

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American Journal of Emergency Medicine

journal homepage: www. elsevier.com/ locate/ajem

Correspondence

Suggestion of a meta-analysis: unfractionated heparin vs Low-molecular-weight heparin in patients with compromised left ventricular function

To the Editor,

Clinical experience teaches us to use intravenous (IV) infusions wisely and not to forget the possibility of sudden worsening of heart function following the infusion, especially in older individuals and patients with known heart disease. It is particularly true for rapid IV infusion given to Older women and patients with heart failure with preserved left ventricular (LV) ejection fraction (LVEF) [1].

Heparin is one of the most frequently used drugs globally [2]. Low-molecular-weight heparins (LMWHs) have many advantages over unfractionated heparin , including one insufficiently recognized: avoiding of a volume load. Namely, “heparin pump” (the usual way of therapeutic UFH doses administration) means volume load (500 mL of fluid per day). This advantage of LMWH is important for patients with manifest HF and those at high risk for it [3]. Many trials in venous thromboembolism had protocols with continuous IV therapeutic UFH administration for 5 to 10 days (up to 14 days) [4]. The amount of fluid received in this way is very high for a patient with compromised heart function. The situation may be complicated by concomitant administration of another infusion (additional volume load)–which frequently occurs in real life (such as nitroglycerin infusion in acute coronary syndrome patients).

Among hospitalized patients, there are 3 basic groups with compromised heart function (or prone to it):

First is HF itself, which causes 5% of acute hospital admissions and is present in 10% of hospitalized patients [5], affecting 2.4% of the adult population and more than 11% of the population older than 80 years [6]. With any-mention deaths, HF accounts for 35% of cardiovascular disease deaths [7].

Second, 25% of acute coronary syndrome have HF signs/symptoms [8]. Significant global LV systolic dysfunction (LVEF <=40%) was observed in 34% of patients with acute myocardial infarction at discharge, and it varies among articles from 27% to 60% [9]. Brain natriuretic peptide 300 pg/mL or higher was found in 34.4% of non- ST-segment elevation myocardial infarction patients [10].

Third, pulmonary thromboembolism is among the most prevalent life-threatening cardiovascular diseases, and HF is very important risk factor for it. In turn, pulmonary thromboembolism is well-recognized cause of HF worsening [11].

Moreover, there are numerous patients prone to HF, for example, with hypertensive LV hypertrophy, with coronary artery disease, valvular diseases, atrial fibrillation, diabetes mellitus, and others. Heparin pump may be additional reason for decompensation.

Similarly, pulmonary edema may arise easily with UFH in- fusion in patients with hypoalbuminemia, which is frequent in hospitalized patients.

Recently, 6 (almost) unrecognized advantages of LMWHs over UFH in pateints with jeopardized heart function have been listed: UFH (given in Therapeutic doses by means of IV infusion) creates volume load, requires immobilization, produces stress, damages veins, raises probability for hyperkalemia, and for heparin resistance [12].

Most hospitalized cardiologic patients have a life-threatening disease, which is also true for patients receiving therapeutic doses of parenteral anticoagulants. Surprisingly, we do not have either large studies or evidences from registries or meta-analyses of trials to create Evidence-based guidelines regarding the choice of parenteral anticoag- ulant for patients with evident or imminent HF. Furthermore, even guidelines rarely address this question, although it is important for everyday work. Recent, high-quality guidelines on HF recommended: “If AF is of >=48 h duration or of unknown duration, heparin by IV bolus should be administered followed by a continuous infusion” [5]. We suggest a meta-analysis of numerous randomized clinical trials comparing UFH and LMWH regarding the outcomes of patients: (1) with diagnosed HF vs without it and (2) with different quintiles or sixtiles of LVEF.

In conclusion, therapeutic doses of parenteral anticoagulants have been administrated to millions of patients a year globally, without any clear, evidence-based recommendation how to choose between LMWH and UFH in patients with compromised heart function. There are dozens of articles, which repeat the advantages of LMWHs over UFH generally (eg, bioavailability) or the other way around (eg, UFH is better in renal failure patients). Low-molecular- weight heparins have numerous advantages in HF specifically, but this is mentioned only in 2 available articles. Theoretical but persuasive advantages of LMWHs over UFH in present (or forthcoming) HF should be checked in meta-analysis of randomized clinical trials, which have the data about patients’ LVEFs. Such an important result should find its place in future guidelines about parenteral anticoagulants.

Acknowledgment

This work has been supported by the Serbian Ministry of Education and Science, grant no.175092.

Goran P. Koracevic MD, PhD

Department of Cardiology, Clinical Centre and Medical Faculty

University of Nis, Nis, Serbia E-mail address: gkoracevic@yahoo.com

http://dx.doi.org/10.1016/j.ajem.2012.12.036

0735-6757/$ – see front matter (C) 2013

References

Correspondence

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in advanced heart failure: a scientific statement from the American Heart Association. Circulation 2012;125:1928-52.

1. Fujimoto N, Borlaug BA, Lewis GD, et al. Hemodynamic responses to rapid saline loading: theimpact of age, sex, and heart failure. Circulation 2012 [Epub ahead of print].
2. Junqueira DR, Perini E, Penholati RR, et al. Unfractionated heparin versus Low Molecular Weight Heparin for avoiding Heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev 2012;9:CD007557: http:

//dx.doi.org/10.1002/14651858.CD007557.pub2.

1. Koracevic GP. LMWHs have additional advantage over unfractionated heparin: no volume load. Swiss Med Wkly 2009;139:642.
2. Kearon C, Kahn SR, Agnelli G, et al. American College of Chest Physicians. antithrombotic therapy for Venous thromboembolic disease: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133(6 Suppl):454S-545S.
3. Dickstein K, Cohen-Solal A, Filippatos G, et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM.Task Force for Diagnosis and Treatment of Acute and Chronic Heart Failure 2008 of European Society of Cardiology. Eur Heart J 2008;29:2388-442.
4. Allen LA, Stevenson LW, Grady KL, et al. American Heart Association; Council on Quality of Care and Outcomes Research; Council on Cardiovascular Nursing; Council on Clinical Cardiology; Council on Cardiovascular Radiology and Intervention; Council on Cardiovascular Surgery and Anesthesia; Decision making
5. Go AS, Mozaffarian D, Roger VL, et al, on behalf of the American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics–2013 Update A Report From the American Heart Association. Circulation 2012 [Epub ahead of print].
6. Weintraub NL, Collins SP, Pang PS, et al. American Heart Association Council on Clinical Cardiology and Council on Cardiopulmonary, Critical Care, Perioperative and Resuscitation. Acute heart failure syndromes: emergency department presentation, treatment, and disposition: current approaches and future aims: a scientific statement from the American Heart Association. Circulation 2010;122: 1975-96.
7. Swiatkiewicz I, Magielski P, Woznicki M, et al. Occurrence and predictors of left ventricular systolic dysfunction at hospital discharge and in long-term follow-up after acute myocardial infarction treated with primary percutaneous coronary intervention. Kardiol Pol 2012;70:329-40.
8. Takada JY, Ramos RB, Avakian SD, et al. BNP and admission glucose as in-hospital Mortality predictors in non-ST elevation myocardial infarction. Scientific World Journal 2012;2012:397915.
9. Torbicki A, Perrier A, Konstantinides S, et al. Guidelines on the diagnosis and management of acute pulmonary embolism: the Task Force for the Diagnosis and Management of Acute Pulmonary Embolism of the European Society of Cardiology (ESC). Eur Heart J 2008;29:2276-315.
10. Koracevic G. Six almost unknown reasons why LMWH is better than unfractio- nated heparin in therapy of patients with present or threatening heart failure. Recent Researches in Modern Medicine, WSEAS 2011:137-141 (ISBN: 978-960- 474-278-3).