September 18, 2020

Use of fondaparinux in non-critically ill patients with COVID-19 “should be discouraged”: Study

Findings from a study published in Thrombosis Research suggest the use of fondaparinux in place of low-molecular-weight heparin (LMWH) in patients with non-critically ill coronavIrus disease 2019 (COVID-19) “should be discouraged.” However, “whether these conclusions apply to patients with a more severe disease remains to be demonstrated,” cautions the study.

“Unlike oral Xa inhibitors, fondaparinux does not interfere with antiviral drugs, and, therefore, it qualifies as a potential candidate to replace LMWH for prevention of thrombotic complications in high-risk patients, such as those admitted to medical departments because of a non-severe COVID-19,” wrote researchers led by Paolo Prandoni, Arianna Foundation, Bologna, Italy.

Researchers retrieved medical charts of non-critically ill COVID-19 patients admitted to seven medical departments in Northern Italy, and compared the incidence of venous and arterial thrombotic complications, as well as that of major and clinically relevant bleeding complications between patients administered with prophylactic doses of enoxaparin and those with fondaparinux. A total of 308 patients were included in the study, whereby 160 had been treated with standard prophylactic doses of 4000 units of enoxaparin and 148 with 2.5 mg of fondaparinux, once daily, which were generally reduced to 2000 units and 1.5 mg, respectively, in patients with severe renal failure. The treatment duration was similar in the two groups: 16.9 ± 8.3 days among enoxaparin recipients and 17.2 ± 6.6 days among fondaparinux recipients (P = 0.80). The demographic and clinical characteristics of the patients receiving enoxaparin and fondaparinux were comparable, with a mean age of 65 and 64, respectively.

The study revealed a similarly proportion of clinically symptomatic and objectively confirmed venous or arterial thrombotic complications in the two study groups, whereby 5 episodes (3.1%) were reported in the enoxaparin group (1 proximal leg DVT, 1 proximal arm DVT, 1 PE, 1 ischemic stroke and 1 fatal coronary syndrome), and 4 episodes (2.7%) in the fondaparinux group (1 proximal leg DVT, 1 PE, 1 fatal and 1 non-fatal coronary syndrome) (P = 0.83). 

In contrast, the researchers found the rate of major or clinically relevant bleeding complications - defined according to the ISTH classification - was “remarkably higher” in patients treated with fondaparinux than in those allocated to enoxaparin (4.7% vs 0.6%, P = 0.03). However, they reported that no fatality was associated with the bleeding complications which included gastrointestinal bleeding, retroperitoneal bleeding and epistaxis. The researchers noted that these complications led to discontinuation of thromboprophylaxis.

Further, the study showed that the number of patients who required admission to intensive care units was similar in both groups (6 among enoxaparin and 4 among fondaparinux recipients), as was the number of patients who died (8 and 7, respectively). 

“While the rate of clinically symptomatic and objectively confirmed venous or arterial thrombotic complications was similar in the two study groups, that of major or clinically relevant bleeding complications was remarkably higher among fondaparinux recipients,” the authors concluded.

“The hemorrhagic potential of fondaparinux in low, prophylactic doses was somewhat unexpected, as it contrasts with that seen in other medical and surgical settings,” the authors noted, adding that it was found to “mirror that of (sub)therapeutic doses of LMWH in the same clinical scenario.” 

“A potential explanation is the frailty of patients, such as those admitted because of a COVID-19 infection, who are on average old and with additional comorbidities, thus more vulnerable when treated with a more potent antithrombotic drug, which in addition possesses a much longer half-life and a higher risk of accumulation (potentially dangerous in patients with infection-related renal impairment),” the authors wrote.

Further, the authors said “although a selection bias is likely to have occurred because of the lack of a randomized allocation to the treatment groups, the conclusions are plausible because of the full comparability in the baseline and clinical characteristics of the recruited patients.” They added that an identical approach was used to identify and classify the thrombotic and hemorrhagic complications according to widely accepted definitions.

SOURCE: Thrombosis Research
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