Safety and efficacy of low-dose fondaparinux (1.5 mg) for the prevention of venous thromboembolism in acutely ill medical patients with renal impairment: the FONDAIR study

Background: Renal impairment is common, affecting
around 40% of acutely ill medical patients, and is associated
with an increased risk of both venous thromboembolism (VTE)
and bleeding. The clinical benefit of effective thromboprophylactic
strategies may be outweighed in these patients by an
excessive rate of hemorrhage. Objective: To assess the safety
and efficacy of lower prophylactic doses of fondaparinux in
acutely ill medical patients with renal impairment. Patients/
Methods: We carried out a multicenter, investigator-initiated,
prospective cohort study. Patients at risk of VTE with a
creatinine clearance between 20 and 50 mL min)1 were treated
with fondaparinux 1.5 mg qd for a minimum of 6 to a
maximum of 15 days. The primary outcome was the incidence
of major bleeding; secondary outcomes were clinically relevant
non-major bleeding (CRNMB) and symptomatic VTE.
Results: We enrolled 206 patients with a mean age of 82 years,
mean creatinine clearance of 33 mL min)1, and a mean
Charlson co-morbidity index of 8.2. One patient had major
bleeding (0.49%, 95% confidence interval [CI] 0.03–3.10), eight
had CRNMB (3.88%, 95% CI 1.81–7.78) and three developed
symptomatic VTE (1.46%, 0.38–4.55). Twenty-three patients
(11.17%, 7.36–16.48) died. No independent predictors of
bleeding were found at univariate analysis. Conclusions: The
addition of moderate to severe renal impairment to patients
with traditional risk factors for VTE identified a population of
very elderly acutely ill medical patients potentially at high risk of
both VTE and bleeding complications. The recently approved
lower prophylactic dose of fondaparinux appears to be a safe
and relatively effective strategy in these patients.