Safety and economic considerations of argatroban use in critically ill patients: a retrospective analysis

Kim, Se-Chan; Tran, Nicole; Schewe, Jens-Christian; Boehm, Olaf; Wittmann, Maria; Graeff, Ingo; Hoeft, Andreas; Baumgarten, Georg

doi:10.1186/s13019-015-0214-0

Cited by 12 publications

(8 citation statements)

References 36 publications

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“…This effect might be even more pronounced when the number of failing organ systems increases [ 18 ]. Our data are consistent with these findings and also support other studies, which also recommended much lower argatroban doses in critically ill patients [ 13 , 19 – 21 ]. There are no specific guidelines for dosing in ARDS patients on extracorporeal gas exchange.…”

Section: Discussionsupporting

confidence: 93%

“…ARDS patients in this study were characterized by relatively severe medical conditions, as reflected by high median APACHE II and SAPS II scores at hospital admission. On average, severity scores were higher than in comparable recent studies [ 13 ] and even higher than in the ALIVE study [ 14 ]. Also, parameters of pulmonary gas exchange and invasiveness of mechanical ventilation indicated severe lung failure.…”

Section: Discussioncontrasting

confidence: 67%

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Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support

Menk

Briem

Weiß

et al. 2017

Ann. Intensive Care

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BackgroundExtracorporeal membrane oxygenation (ECMO) or pumpless extracorporeal lung assist (pECLA) requires effective anticoagulation. Knowledge on the use of argatroban in patients with acute respiratory distress syndrome (ARDS) undergoing ECMO or pECLA is limited. Therefore, this study assessed the feasibility, efficacy and safety of argatroban in critically ill ARDS patients undergoing extracorporeal lung support.MethodsThis retrospective analysis included ARDS patients on extracorporeal lung support who received argatroban between 2007 and 2014 in a single ARDS referral center. As controls, patients who received heparin were matched for age, sex, body mass index and severity of illness scores. Major and minor bleeding complications, thromboembolic events, administered number of erythrocyte concentrates, thrombocytes and fresh-frozen plasmas were assessed. The number of extracorporeal circuit systems and extracorporeal lung support cannulas needed due to clotting was recorded. Also assessed was the efficacy to reach the targeted activated partial thromboplastin time (aPTT) in the first consecutive 14 days of therapy, and the controllability of aPTT values is within a therapeutic range of 50–75 s. Fisher’s exact test, Mann–Whitney U tests, Friedman tests and multivariate nonparametric analyses for longitudinal data (MANOVA; Brunner’s analysis) were applied where appropriate.ResultsOf the 535 patients who met the inclusion criteria, 39 receiving argatroban and 39 matched patients receiving heparin (controls) were included. Baseline characteristics were similar between the two groups, including severity of illness and organ failure scores. There were no significant differences in major and minor bleeding complications. Rates of thromboembolic events were generally low and were similar between the two groups, as were the rates of transfusions required and device-associated complications. The controllability of both argatroban and heparin improved over time, with a significantly increasing probability to reach the targeted aPTT corridor over the first days (p < 0.001). Over time, there were significantly fewer aPTT values below the targeted aPTT goal in the argatroban group than in the heparin group (p < 0.05). Both argatroban and heparin reached therapeutic aPTT values for adequate application of extracorporeal lung support.ConclusionsArgatroban appears to be a feasible, effective and safe anticoagulant for critically ill ARDS patients undergoing extracorporeal lung support.

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Section: Discussionsupporting

confidence: 93%

Section: Discussioncontrasting

confidence: 67%

Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support

Menk

Briem

Weiß

et al. 2017

Ann. Intensive Care

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“…Argatroban has been used for anticoagulation in patients with heparin-induced thrombocytopenia since two prospective studies in patients without ECMO showed a reduction in the composite endpoint (thrombosis, amputation, and death) in comparison to historical controls [ 11 , 39 ]. Data from a retrospective study on patients with HIT showed a reduction in overall treatment costs despite the fact that absolute drug costs of Argatroban are 17 times higher than those of UFH, mainly because of reduced costs of transfusions [ 40 ]. Coughlin et al [ 6 ] reported that overall costs of DTI are comparable to those of UFH after accounting for complications and additional tests.…”

Section: Discussionmentioning

confidence: 99%

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Fisser¹,

Winkler²,

Malfertheiner³

et al. 2021

Crit Care

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Background During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. Methods We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). Results Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). Conclusion In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

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“…Of these, 309 were excluded because no new data were given ( n = 130), insufficient clinical data reported ( n = 44), double publication ( n = 81), case reports only ( n = 9), or used an investigational therapy other than one of the pre‐specified anticoagulants ( n = 45). Ninety‐two articles reporting on 4698 patients in 119 study groups were eventually included 20‐111 . A flow‐diagram of the articles is illustrated in Figure 1.…”

Section: Resultsmentioning

confidence: 99%

Comparative effectiveness and safety of anticoagulants for the treatment of heparin‐induced thrombocytopenia

et al. 2021

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Background The effectiveness and safety of non‐heparin anticoagulants for the treatment of heparin‐induced thrombocytopenia (HIT) are not fully established, and the optimal treatment strategy is unknown. In a systematic review and meta‐analysis, we aimed to determine precise rates of platelet recovery, new or progressive thromboembolism (TE), major bleeding, and death for all non‐heparin anticoagulants and to study potential sources of variability. Methods Following a detailed protocol (PROSPERO: CRD42020219027), EMBASE and Medline were searched for all studies reporting clinical outcomes of patients treated with non‐heparin anticoagulants (argatroban, danaparoid, fondaparinux, direct oral anticoagulants [DOAC], bivalirudin, and other hirudins) for acute HIT. Proportions of patients with the outcomes of interest were pooled using a random‐effects model for each drug. The influence of the patient population, the diagnostic test used, the study design, and the type of article was assessed. Results Out of 3194 articles screened, 92 studies with 119 treatment groups describing 4698 patients were included. The pooled rates of platelet recovery ranged from 74% (bivalirudin) to 99% (fondaparinux), TE from 1% (fondaparinux) to 7% (danaparoid), major bleeding from 1% (DOAC) to 14% (bivalirudin), and death from 7% (fondaparinux) to 19% (bivalirudin). Confidence intervals were mostly overlapping, and results were not influenced by patient population, diagnostic test used, study design, or type of article. Discussion Effectiveness and safety outcomes were similar among various anticoagulants, and significant factors affecting these outcomes were not identified. These findings support fondaparinux and DOACs as viable alternatives to conventional anticoagulants for treatment of acute HIT in clinical practice.

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Safety and economic considerations of argatroban use in critically ill patients: a retrospective analysis

Cited by 12 publications

References 36 publications

Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support

Efficacy and safety of argatroban in patients with acute respiratory distress syndrome and extracorporeal lung support

Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Comparative effectiveness and safety of anticoagulants for the treatment of heparin‐induced thrombocytopenia

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