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Fondaparinux safe in renal impairment – – Drug Topics.

Fondaparinux safe in renal impairment
By: Anna D. Garrett, PharmD, BCPS

Anna D. Garrett, PharmD, BCPSPatients with renal impairment often need prophylaxis for venous thromboembolism (VTE); however, clinical trial data on anticoagulants are limited in this population.

A recently published prospective study examined the safety and efficacy of fondaparinux in patients with a creatinine clearance (CrCl) of 20 to 50 mL/min. Patients who were undergoing total hip replacement, total knee replacement, or hip fracture surgery received fondaparinux thromboprophylaxis at a reduced dose of 1.5 mg daily. Main clinical outcomes were bleeding (major/clinically relevant non-major), symptomatic VTE, and death. A total of 442 patients (median age, 82 years) with a mean CrCl of 39 mL/min received fondaparinux 1.5 mg for a mean duration of 16 days.

Rates of major bleeding, clinically relevant bleeding, and symptomatic VTE were 4.5%, 0.5%, and 0.5%, respectively, at postoperative day 10. No incidences occurred of fatal bleeding, bleeding into a critical organ, pulmonary embolism, or proximal deep-vein thrombosis. Corresponding rates at 1 month were 5.2%, 0.7%, and 0.7%, respectively, with a 1-month mortality of 2.3%.

Under conditions reflecting “real-world” routine clinical practice, this large clinical, prospective study provides data for the first time on the bleeding and VTE risks of thromboprophylaxis with fondaparinux 1.5 mg after major orthopedic surgery in renally impaired patients.

Source: Mismetti P, Samama CM, Rosencher N, et al; for The PROPICE Study Group. Venous thromboembolism prevention with fondaparinux 1.5 mg in renally impaired patients undergoing major orthopaedic surgery. A real-world, prospective, multicentre, cohort study. Thromb Haemost.2012;107:1151–1160.

Aspirin vs. warfarin for stroke prevention in CHF

Congestive heart failure (CHF) is associated with an increased risk of thrombus formation and is accompanied by a 2- to 3-fold increased risk of stroke. Stroke in CHF patients is associated with poor outcome and higher mortality. For these reasons, patients with CHF are often treated with warfarin to prevent blood clots.

A recent international double-blind, study of 2,305 patients with heart failure and normal sinus rhythm found that aspirin works just as well as warfarin. In this study, half of the subjects were given regimens of warfarin and placebo, while the other half received aspirin and placebo warfarin. The patients were followed for up to 6 years, with the primary outcome defined as time to the first event in the composite end point of ischemic stroke, intracerebral hemorrhage, or death.

Overall, whether patients were treated with warfarin or aspirin, there was no significant difference in the primary outcome (7.47 events/100 patient-years in the warfarin group vs 7.93 events/100 patient-years in the aspirin group; P=.40). Patients who took warfarin were significantly less likely to have a stroke, but that advantage was negated by an increased likelihood of gastrointestinal bleeding and other hemorrhages. There were no significant differences in rates of myocardial infarction or hospitalizations for heart failure.

Source: Homma S, Thompson JLP, Pullicino PM, et al; for the WARCEF Investigators. Warfarin and aspirin in patients with heart failure and sinus rhythm. N Engl J Med. 2012;366:1859–1869.

tPA safe in patients on warfarin

An analysis of data from the American Heart Association Get With The Guidelines (GWTG)-Stroke Registry shows that acute ischemic stroke patients on warfarin with an international normalized ratio (INR) <1.7 can safely receive intravenous tissue plasminogen activator (tPA) without an increased risk of symptomatic intracranial hemorrhage (sICH).

A separate analysis of patients with ischemic stroke receiving warfarin in the GWTG-Stroke Registry showed that about 48% of warfarin-treated tPA-eligible patients with acute ischemic stroke do not receive tPA. Intravenous tPA remains the only effective treatment to improve stroke outcomes.

Current guidelines recommend intravenous tPA for ischemic stroke in warfarin-treated patients when the INR is <1.7. Yet there is considerable debate regarding the risk of sICH in warfarin-treated patients and a lack of safety data.

Study authors analyzed data on 23,437 patients with acute ischemic stroke who received tPA in more than 1,200 GWTG-Stroke hospitals between April 1, 2009, and June 30, 2011. Among these were 1,802 patients (7.7%) receiving warfarin prior to admission. Overall, 1,107 patients (4.7%) developed sICH after receiving tPA. Warfarin-treated patients were found to have a higher overall unadjusted rate of sICH relative to nonwarfarin-treated patients (5.7% vs 4.6%; P<.001). After risk adjustment, however, warfarin use was not an independent predictor of sICH risk.

The researchers cautioned that further study is needed to clarify the effectiveness and safety of tPA for patients beyond the recommended INR range of <1.7.

Source: Xian Y, Liang L, Smith EE, et al. Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator. JAMA. 2012;307:2600–2608.

Anna D. Garrett is a clinical pharmacist and president of Find Your Best Thinking, a health and wellness coaching company. Contact her at

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