|Year : 2019 | Volume
| Issue : 3 | Page : 122-125
A retrospective observational study to compare the safety of fondaparinux versus enoxaparin among patients who underwent hemiarthroplasty
Sangeetha Gopinath1, Anoop S Pillai2
1 Department of Pharmacology, SUT Academy of Medical Science (SUTAMS), Thiruvananthapuram, Kerala, India
2 Department of Orthopedics, SUT Academy of Medical Science (SUTAMS), Thiruvananthapuram, Kerala, India
|Date of Submission||09-Nov-2019|
|Date of Acceptance||14-Nov-2019|
|Date of Web Publication||27-Nov-2019|
Dr. Anoop S Pillai
Department of Orthopedics, SUT Academy of Medical Science (SUTAMS), Vattappara, Thiruvananthapuram, Kerala
Source of Support: None, Conflict of Interest: None
Background: Major orthopedic surgeries carry a high risk of venous thromboembolism. Enoxaparin has been in use for this indication for a long time. Fondaparinux, a relatively new anticoagulant, has also shown favorable results. Till date, there are limited studies comparing the safety of fondaparinux with enoxaparin in Indian patients undergoing major orthopedic surgery. Aim: The aim of this study was to compare the safety of fondaparinux with enoxaparin in the real-life setting. Materials and Methods: Patients who underwent hemiarthroplasty between January 2016 and December 2017, and who were administered fondaparinux or enoxaparin were retrospectively analyzed using patient case files, discharge database, and blood bank database. The safety was assessed based on the requirement of blood transfusion, need for reexploration, wound complications, any occurrence of bleeding, and death from all causes. Pearson’s chi-square test was used using the Statistical Package for the Social Sciences (SPSS) software (IBM, India), version 16. Results: The safety profile of fondaparinux was comparable with enoxaparin with regard to occurrence of bleeding, transfusion requirements, wound complications, and need for reexploration. A higher proportion of patients on fondaparinux had to be given blood transfusion, though this difference was not statistically significant (P = 0.120). Conclusion: In patients who underwent hemiarthroplasty, safety of fondaparinux was comparable to enoxaparin in actual clinical experience.
Keywords: Enoxaparin, Fondaparinux, Hemiarthroplasty, Safety
|How to cite this article:|
Gopinath S, Pillai AS. A retrospective observational study to compare the safety of fondaparinux versus enoxaparin among patients who underwent hemiarthroplasty. J Health Res Rev 2019;6:122-5
|How to cite this URL:|
Gopinath S, Pillai AS. A retrospective observational study to compare the safety of fondaparinux versus enoxaparin among patients who underwent hemiarthroplasty. J Health Res Rev [serial online] 2019 [cited 2020 Sep 29];6:122-5. Available from: http://www.jhrr.org/text.asp?2019/6/3/122/271845
| Introduction|| |
Deep venous thrombosis (DVT) represents one of the most frequent and dreaded postoperative complications in major orthopedic surgeries.
There is a risk of approximately 2.5% for deep vein thrombosis, and 1% for nonfatal pulmonary embolism after hip and knee arthroplasty.
The American College of Chest Physicians Evidence-Based Clinical Practice guidelines suggest that thromboprophylaxis can be either pharmacological or mechanical. The preferred pharmacologic agents include low-molecular-weight heparin (such as dalteparin or enoxaparin) or a pentasaccharide (such as fondaparinux).
Fondaparinux is a new class of anticoagulant that acts by inhibiting factor Xa, with no activity against thrombin (factor IIa). Enoxaparin inhibits both factor IIa (thrombin) and factor Xa.
When compared to the Western population, the occurrence of DVT is surmised to be low in the Indian population. Because of this low incidence, routine chemoprophylaxis is not considered cost-effective in Indian patients undergoing major orthopedic surgeries, who have no known risk factors for DVT., But some recent studies have shown that there is an increased occurrence of DVT in the Indian population.,, This has been attributed to increased life expectancy and better methods of diagnosis. These studies recommend that routine chemoprophylaxis is justified in the Indian population.
Most studies have shown that fondaparinux is associated with a higher risk of bleeding., We undertook this study to bridge the gap between evidence-based guidelines and everyday clinical practice.
The purpose of our study was to compare the safety of fondaparinux to enoxaparin in actual clinical experience.
| Materials and Methods|| |
This was a retrospective observational study. The study protocol was approved by the institutional ethics committee (IEC01/6/2018 SUTAMS). The main objective of this study was to compare the safety of both drugs by assessing the postoperative blood transfusion requirement, need for reexploration, wound complications, bleeding events, and all-cause mortality.
All patients who underwent hemiarthroplasty by the same surgeon, between January 2016 and December 2017, were retrospectively analyzed using patient charts, hospital admission, discharge database, and blood bank database.
Patient details were documented. The occurrence of severe bleeding, transfusion requirements, wound complications, requirement for reexploration, and death was also assessed.
Patient sampling criteria
Patients who underwent elective hemiarthroplasty by the same surgeon were included in the study. They were eligible if they were older than 60 years and received postoperative thromboprophylaxis with either 2.5 mg subcutaneous fondaparinux (Arixtra; Glaxosmithkline Beecham, Mumbai) or 60mg enoxaparin (Clexane; Sanofi Aventis, Mumbai). Patients were excluded if they were pregnant, had a history of congenital or acquired bleeding disorder, had heart failure, uncontrolled hypertension, liver dysfunction, renal impairment, and were on oral anticoagulant or antiplatelet treatment.
The safety outcome was assessed by occurrence of bleeding, postoperative blood loss, and blood replacement requirements. The number of transfused whole blood units, plasma expanders, or packed red blood cells was documented.
Major bleeding was defined as any fatal bleeding, bleeding into a critical organ (e.g., retroperitoneal, intracranial, intraocular, or intraspinal), clinically overt (e.g., gastrointestinal) bleeding associated with a ≥2g/dL drop in hemoglobin level or requiring ≥2 units of blood transfused, and bleeding leading to reoperation. Minor bleeding was defined as bleeding that did not fulfill the criteria for major bleeding.
Documented complications such as minor soakage of wound, delayed suture removal, requirement of reexploration, superficial or deep infections, and death were also noted.
The two treatment groups were investigated for differences in baseline variables. Qualitative analysis was carried out using Pearson’s chi-square test to compare the data. All data were statistically analyzed using the Statistical Package for the Social Sciences software (IBM), version 16.
| Results|| |
Between January 2016 and December 2017, 71 patients underwent hemiarthroplasty by the same surgeon. Of these, 35 patients (49.3%) received fondaparinux, whereas 36 patients (50.7%) received enoxaparin.
The baseline characteristics did not differ significantly between the two groups [Table 1]. Similarly, specific surgical characteristics were comparable between the two groups.
Bleeding and transfusion requirements
The safety of fondaparinux was comparable to enoxaparin with regard to severe bleeding as well as for the requirement of blood transfusions [Table 2].
Of the 71 patients, 38 patients (53.5%) received blood transfusion postoperatively. Of these, a higher proportion of patients on fondaparinux (22) had to be given blood transfusion, though this difference was not statistically significant (P = 0.120).
Major bleeding occurred in two patients receiving fondaparinux compared to one event in patients receiving enoxaparin. No instances of fatal bleeding or bleeding were observed in a critical organ in either treatment groups.
The occurrence of minor bleeding was comparable in both groups.
The occurrence of minor soakage was low and did not differ significantly between the groups: 14.3% (5 of 35 patients) in those receiving fondaparinux compared to 8.3% (3 of 36 patients) in the enoxaparin group.
Similarly, the occurrence of delayed suture removal did not differ between the groups: 5.7% (2 of 35 patients) in the fondaparinux group and 2.8% (1 of 36 patients) in the enoxaparin group.
Need for exploration
Two patients on fondaparinux required reexploration in contrast to none in the enoxaparin group. This was not found to be statistically significant.
| Discussion|| |
Our study shows that the occurrence of major and minor bleeding events did not differ significantly between fondaparinux and enoxaparin. Though the rates of transfusion and bleeding events tended to be on a higher side for those receiving fondaparinux, this difference was not found to be statistically significant.
This is in odds with most of the clinical trials comparing both drugs. Most of the clinical trials have shown that the use of fondaparinux is associated with a higher risk of bleeding,, whereas others have shown that fondaparinux has comparable safety to enoxaparin.,
In a study by Eriksson et al. and Lassen et al., the frequency of major hemorrhagic events did not differ between the fondaparinux and enoxaparin groups, in patients who underwent hip arthroplasty. Transfusion requirements were comparable, although minor bleeding occurred more often in the fondaparinux group.
In a study on major knee surgery by Bauer et al., major bleeding occurred more frequently in the fondaparinux group (P = 0.006), but there were no significant differences between the two groups in the incidence of minor bleeding, transfusion requirements, or fatal bleeding.
The meta analysis by Turpie et al. too pointed out that although major bleeding was significantly higher in the fondaparinux-treated group, the incidence of clinically relevant bleeding (leading to death or reoperation or occurring in a critical organ) did not differ between groups.
The results obtained from a large registry-based study, conducted in Dresden, Germany, are at odds with the results obtained from clinical trials. The study depicted a higher rate of transfusion requirement in the patients who were administered enoxaparin, though the rates of severe bleeding were comparable between both treatment groups.
More number of patients required reoperation because of bleeding in a study by Eriksson et al. This trend was also pointed out in a study by Donath et al. where patients receiving fondaparinux had significantly less surgical complications requiring surgical revisions. The mean length of hospital stay was significantly shorter in the fondaparinux group. This is in contrast to the data from trials in which the rates of postoperative complications were comparable.
Our study was a retrospective observational study. The sample size was small. Our study indicated that both drugs are equally safe but more studies with a larger population have to be carried out to ascertain the safety of each drug in specific clinical settings.
We would like to thank Dr. Anitha Abraham, Associate Professor, Department of Community Medicine, SUTAMS, Thiruvananthapuram, Kerala, India, for helping with the statistical analysis of our study.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Edelsberg J, Ollendorf D, Oster G. Venous thromboembolism following major orthopedic surgery: Review of epidemiology and economics. Am J Health Syst Pharm 2001;58:S4-13.
Falck-Ytter Y, Francis CW, Johanson NA, Curley C, Dahl OE, Schulman S, et al
. Prevention of VTE in orthopedic surgery patients: Antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-based Clinical Practice Guidelines. Chest 2012;141:e278-325S.
Lieberman JR, Hsu WK. Prevention of venous thromboembolic disease after total hip and knee arthroplasty. J Bone Joint Surg Am 2005;87:2097-112.
Lee AD, Stephen E, Agarwal S, Premkumar P. Venous thrombo-embolism in India. Eur J Vasc Endovasc Surg 2009;37:482-5.
Mavalankar AP, Majmundar D, Rani S. Routine chemoprophylaxis for deep venous thrombosis in Indian patients: Is it really justified? Indian J Orthop 2007;41: 188-93.
] [Full text]
Jain V, Dhaon BK, Jaiswal A, Nigam V, Singla J. Deep vein thrombosis after total hip and knee arthroplasty in Indian patients. Postgrad Med J 2004;80:729-31.
Todi SK, Sinha S, Chakraborthy A, Sarkar A, Gupta S, Das T, et al
. Utilisation of deep venous thrombosis prophylaxis in medical/surgical intensive care units. Indian J Crit Care Med 2003;7:103-5. [Full text]
Sen RK, Tripathy SK, Singh AK. Is routine thromboprophylaxis justified among Indian patients sustaining major orthopedic trauma? A systematic review. Indian J Orthop 2011;45:197-207.
] [Full text]
Rahul S, Sameer A, Vishal K, Prasoon K, Sandeep P. Acute venous thromboembolism in Indian patients of isolated proximal femur fractures. J Clin Orthop Trauma 2019;10:917-21.
Parakh R, Kakkar VV, Kakkar AK. Venous Thromboembolism (VTE) Core Study Group. Management of venous thromboembolism. J Assoc Physicians India 2007;55:49-70.
Bauer KA, Eriksson BI, Lassen MR, Turpie AG. Steering Committee of the Pentasaccharide in Major Knee Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery. N Engl J Med 2001;345:1305-10.
Migita K, Bito S, Nakamura M, Miyata S, Saito M, Kakizaki H, et al
. Venous thromboembolism after total joint arthroplasty: Results from a Japanese multicenter cohort study. Arthritis Res Ther 2014;16:R154.
Eriksson BI, Bauer KA, Lassen MR, Turpie AG. Steering Committee of the Pentasaccharide in Hip-Fracture Surgery Study. Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery. N Engl J Med 2001;345:1298-304.
Lassen MR, Bauer KA, Eriksson BI, Turpie AG; European Pentasaccharide Elective Surgery Study (EPHESUS) Steering Committee. Postoperative fondaparinux versus preoperative enoxaparin for prevention of venous thromboembolism in elective hip-replacement surgery: A randomised double-blind comparison. Lancet 2002;359:1715-20.
Turpie AG, Bauer KA, Eriksson BI, Lassen MR. Fondaparinux vs. enoxaparin for the prevention of venous thromboembolism in major orthopedic surgery: A meta-analysis of 4 randomized double-blind studies. Arch Intern Med 2002;162:1833-40.
Donath L, Lützner J, Werth S, Kuhlisch E, Hartmann A, Günther KP, et al
. Efficacy and safety of venous thromboembolism prophylaxis with fondaparinux or low molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery—Findings from the ORTHO-TEP Registry. Br J Clin Pharmacol 2012;74:947-58.
[Table 1], [Table 2]