Warfarin does not decrease risk of stroke in dialysis patients

Anna GarrettOral anticoagulation therapy (OAT) is the treatment of choice for clot prevention in hemodialysis (HD) patients, although data are contradictory regarding efficacy. A recent Italian study evaluated the effect of OAT on the risk of mortality, stroke, and bleeding in a population of HD patients with atrial fibrillation (AF). Patients were followed for two years. OAT and antiplatelet intake, age, dialytic age, comorbidities, and percentage time in the target therapeutic range (TTR) were considered as predictors of hazard of death, thromboembolic events, and bleeding.

See also: Oral anticoagulation may not help all AF patients

At recruitment, 134 patients out of 290 were taking OAT. During the follow-up, 115 patients died (four from strokes: three hemorrhagic and one thromboembolic). Antiplatelet therapy, but not OAT, was associated with increased mortality. Survival of patients who were adherent with OAT was better than that of patients who stopped taking it. OAT was not correlated to a significant decreased risk of thromboembolic events, but it was associated with an increased risk of bleeding. Higher TTR was associated with a reduced bleeding risk , while previous hemorrhagic events were associated with higher hemorrhagic risk.

Mortality in HD patients with AF is very high. In this study, OAT was not associated with increased mortality, and did not appear to decrease the risk of ischemic stroke.

Source: Genovesi S, Rossi E, Gallieni M, et al.Warfarin use, mortality, bleeding and stroke in haemodialysis patients with atrial fibrillation. Nephrol Dial Transplant. 2015;30(3):491–498.

Correction of INR and elevated BP improves outcomes in ICH

Use of oral anticoagulant therapy (OAT) is increasing, but there is a substantial lack of data on how to treat OAT-associated intracerebral hemorrhage (ICH).

See also: Aspirin fails in Japanese primary prevention study

To assess the association of anticoagulation reversal and blood pressure (BP) with hematoma enlargement and the effects of OAT resumption, a retrospective cohort study was conducted at 19 German tertiary care centers. Investigators included 1,176 patients for analysis of long-term functional outcome, 853 for analysis of hematoma enlargement, and 719 for analysis of OAT resumption.

The primary outcomes were frequency of hematoma enlargement in relation to international normalized ratio (INR) and BP, analysis of ischemic and hemorrhagic events with or without OAT resumption and factors associated with favorable (modified Rankin Scale score, 0-3) vs. unfavorable functional outcome.

Hemorrhage enlargement occurred in 307 of 853 patients (36.0%). Reduced rates of hematoma enlargement were associated with reversal of INR levels <1.3 within four hours after admission and systolic BP <160 mm Hg at four hours. The combination of INR reversal <1.3 within four hours and systolic BP of <160 mm Hg at four hours was associated with even lower rates of hematoma enlargement and in-hospital mortality. OAT was resumed in 172 of 719 survivors (23.9%). Restarting therapy resulted in fewer ischemic complications and an insignificant difference in hemorrhagic complications. Functional long-term outcome was unfavorable in 786 of 1083 patients (72.6%).

Source: Kuramatsu JB, Gerner ST, Schellinger PD, et al. Anticoagulant reversal, blood pressure levels, and anticoagulant resumption in patients with anticoagulation-related intracerebral hemorrhage. JAMA 2015;313:824–836.

Reversal agent for NOACs achieves orphan status

Andexanet alfa, a U.S. Food and Drug Administration (FDA)-designated breakthrough therapy, has been granted orphan drug designation by the FDA. The drug reverses the anticoagulant effect of direct or indirect Factor Xa inhibitors in patients experiencing a serious uncontrolled bleeding event or who require urgent or emergent surgery. Currently, there is no approved agent for this use.

Currently, millions of patients are treated with Factor Xa inhibitors for short-term use or chronic conditions. Recent patient data confirm earlier clinical trial results showing that, annually, between 1% and 4% of patients treated with Factor Xa inhibitors may experience major bleeding, and an additional 1% may require emergency surgery.

More than 100,000 U.S. patients are currently affected and could potentially benefit from an antidote. With the expected increase in adoption of these anticoagulants, Portola Pharmaceuticals projects that this number will increase by the year 2020 to up to 200,000 patients in the United States and an estimated 500,000 patients in the G7 countries.

Source: Portola Pharmaceuticals Receives FDA Orphan Drug Designation for Andexanet Alfa, Its Breakthrough-Designated Factor Xa Inhibitor Antidote. [press release] South San Francisco, CA . February 26, 2015. http://bit.ly/andexanetalfa. Accessed March 1, 2015.