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Correspondence |

Clarification of Once-Daily Low-Molecular-Weight Heparin Dosing in Pulmonary EmbolismEnoxaparin Dosing in Pulmonary Embolism FREE TO VIEW

Andrew R. Miesner, PharmD, BCPS; CoraLynn B. Trewet, PharmD, BCPS, CDE
Author and Funding Information

From the Department of Internal Medicine (Dr Miesner), Broadlawns Medical Center, Drake University College of Pharmacy & Health Sciences; and Broadlawns Family Health Center (Dr Trewet), University of Iowa College of Pharmacy.

Correspondence to: Andrew R. Miesner, PharmD, BCPS, Drake University College of Pharmacy & Health Sciences, 2507 University Ave, Harvey-Ingham Hall 126, Des Moines, IA 50311; e-mail: andrew.miesner@drake.edu


Financial/nonfinancial disclosures: The authors have reported to CHEST that no potential conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2012;142(4):1074-1075. doi:10.1378/chest.12-1234
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To the Editor:

We wish to clarify the dosing recommendations of low-molecular-weight heparin (LMWH) in the treatment of acute pulmonary embolism (PE) as discussed by Kearon et al1 in an issue of CHEST (February 2012). According to Kearon et al,1 American College of Chest Physicians (ACCP) Recommendation 5.4.2 states “in patients with acute PE treated with LMWH, we suggest once- over twice-daily administration.” The authors note that “this recommendation only applies when the approved once-daily regimen uses the same daily dose as the twice-daily regimen (ie, the once-daily injection contains double the dose of each twice-daily injection).”1 LMWH agents are pharmacokinetically dissimilar and, consequently, dosing approaches vary, as indicated by Garcia et al.2 The dosing strategies of LMWHs used in the United States for treating acute PE are listed in Table 1.3 Noticeably, the approved daily regimen of enoxaparin does not equal “double the dose of each twice-daily injection.” Thus, should enoxaparin be included in this recommendation?

Table Graphic Jump Location
Table 1 LMWH Agents Available in the United States3

LMWH = low-molecular-weight heparin; PE = pulmonary embolism.

a 

Typical accepted dosing strategy. Dalteparin is not approved by the US Food and Drug Administration for acute VTE other than extended treatment of VTE in patients with cancer.

Throughout the ACCP guideline, seven comparative studies of various LMWH agents dosed once-daily for VTE are cited. Three included patients with PE; only one trial used daily enoxaparin.4 In this trial, patients with acute VTE were randomized to receive heparin or enoxaparin dosed at either 1 mg/kg bid or 1.5 mg/kg daily. Only 31.9% of the patients enrolled had PE at randomization; 94 of these patients received daily enoxaparin. There were no differences in recurrence of thromboembolism between the two dosing strategies in patients who had PE at baseline, but this trial was not adequately powered to assess this specific subgroup.

Given the wording of Recommendation 5.4.2 in Kearon et al,1 many providers may inappropriately prescribe enoxaparin at 2 mg/kg daily or 1.5 mg/kg daily if they fail to read beyond the executive summary. Based on the cited studies, the authors did not intend for these doses to be used in the treatment of acute PE at all, but misinterpretation is likely if the reader is not vigilant. Such has occurred in our institution. A statement in the section regarding treatment of DVT clarifies that 2 mg/kg daily is not used, but this is not mentioned among the recommendations for treatment of PE.1 The paucity of data for 1.5 mg/kg daily limits this dose as well.4

Enoxaparin is the top-selling LMWH in the United States.5 Its use is likely to increase with its recent generic approval. With the widespread use of enoxaparin, broad applications of inappropriate dosing strategies for PE could potentially increase hemorrhagic risks (2 mg/kg daily) or possibly embolic risks (1.5 mg/kg daily). We suggest that providers continue to dose enoxaparin bid for the treatment of acute PE.

Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e419S-e494S. [PubMed] [CrossRef]
 
Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e24S-e43S.
 
Micromedex (Micromedex Drug Information) [mobile application]. Version 1.33.0b1180. New York, NY: Thompson Reuters (Healthcare) Inc. Accessed May 8, 2012.
 
Merli G, Spiro TE, Olsson CG, et al;; Enoxaparin Clinical Trial Group Enoxaparin Clinical Trial Group. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med. 2001;134(3):191-202.
 
IMS Health. The use of medicines in the United States: review of 2010. IMS Institute for Healthcare Informatics website. http://www.imshealth.com/ims/Global/Content/Insights/IMS%20Institute%20for%20Healthcare%20Informatics/IHII_UseOfMed_report1_.pdf. Accessed May 8, 2012.
 

Figures

Tables

Table Graphic Jump Location
Table 1 LMWH Agents Available in the United States3

LMWH = low-molecular-weight heparin; PE = pulmonary embolism.

a 

Typical accepted dosing strategy. Dalteparin is not approved by the US Food and Drug Administration for acute VTE other than extended treatment of VTE in patients with cancer.

References

Kearon C, Akl EA, Comerota AJ, et al. Antithrombotic therapy for VTE disease: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e419S-e494S. [PubMed] [CrossRef]
 
Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012;141(2):e24S-e43S.
 
Micromedex (Micromedex Drug Information) [mobile application]. Version 1.33.0b1180. New York, NY: Thompson Reuters (Healthcare) Inc. Accessed May 8, 2012.
 
Merli G, Spiro TE, Olsson CG, et al;; Enoxaparin Clinical Trial Group Enoxaparin Clinical Trial Group. Subcutaneous enoxaparin once or twice daily compared with intravenous unfractionated heparin for treatment of venous thromboembolic disease. Ann Intern Med. 2001;134(3):191-202.
 
IMS Health. The use of medicines in the United States: review of 2010. IMS Institute for Healthcare Informatics website. http://www.imshealth.com/ims/Global/Content/Insights/IMS%20Institute%20for%20Healthcare%20Informatics/IHII_UseOfMed_report1_.pdf. Accessed May 8, 2012.
 
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