Renal dysfunction ups stroke risk in AF

Limited data are available on the impact of renal function on the outcome of patients with atrial fibrillation. A recently published European study assessed the impact of kidney dysfunction on the outcomes of anticoagulated  patients.

The study compared fixed-dose idraparinux (a pentasaccharide) to conventional anticoagulation with dose-adjusted vitamin K antagonists. Over 4,500 patients were included in the study. There were 45 strokes and 103 major bleeding events that occurred following an average follow-up of 325 ± 164 days.

Patients with CrCl >90 mL/min had an annual stroke/systemic embolus (SE) rate of 0.6%, compared with 0.8% for those with CrCl 60–90 mL/min and 2.2% for those with CrCl <60 mL/min. After adjusting for stroke risk factors, patients with CrCl <60 mL/min had a more than two-fold higher risk of stroke/SE and an almost 60% higher risk of major bleeding compared with those with CrCl ≥60. In patients with the CHA₂DS₂-VASc score 1–2, CrCl <60 mL/min was associated with eight-fold higher stroke/SE risk.

The study was stopped early, due to the number of bleeding events in the idraparinux group.

Source: Apostolakis S, Yuotao G, Lane DA et al. Renal function and outcomes in anticoagulated patients with nonvalvular atrial fibrillation: the AMADEUS trial. Eur Heart J. 2013;34:3572–3579.

Warfarin may increase stroke risk in early treatment

A new study suggests that warfarin, which is prescribed to prevent strokes related to atrial fibrillation, may actually increase the risk in the first 30 days of treatment.

Canadian researchers analyzed data from 70,766 patients, ages 18 or over, who were diagnosed with atrial fibrillation between 1993 and 2008. Patients were followed for up to 16 years until an ischemic stroke, death, end of registration with their primary care practice, or end of the study period occurred, whichever came first.

A total of 5,519 patients experienced a stroke (2% per year). During the first 30 days after starting warfarin, there was a 71% increased risk of ischemic stroke when compared with patients not taking anticoagulant drugs. The highest risk was in the first week of use, peaking on the third day after the patient started warfarin, when there was a 133% increased risk of stroke. Patients with a history of previous ischemic stroke had a 245% (2.5-fold) increased risk during the first 30 days.

Source: Azoulay L, Dell’Aniello S, Simon TA, et al. Initiation of warfarin in patients with atrial fibrillation: Early effects on ischemic strokes. Eur Heart J 2013;doi:10.1093/eurheartj/eht499.

Genetic testing does not improve warfarin dosing

A new study has determined that warfarin dosing based on genetic testing is no better than using standardized dosing methods. Two gene variants, CYP2C9 and VKORC1, can greatly affect a patient’s dose, and tests to determine whether an individual has either of these variants have been available for several years.

The four-year study included 1,015 patients randomly assigned to one of two groups during the first five days after commencement of warfarin therapy. Patients were divided into groups using clinical information alone or clinical information plus specific genetic information. For the patients in the clinical-information dosing group, the initial warfarin dose was determined with information such as age, sex, weight, ethnicity, and the use of other medications. In the genetic-testing group, the same clinical information determined the initial dose, along with information about identified CYP2C9 and VKORC1 variants.

The researchers found that there was no difference between the two groups in mean percentage of time in therapeutic range (PTTR) for the medication (45.2% in the pharmacogenetic-dosing group vs. 45.4% in the clinical-guided dosing group) at four weeks. There was, however, a statistically significant difference by race. Pharmacogenetic-based dosing led to more over-anticoagulation and a longer time to first therapeutic levels of warfarin among African Americans.

The authors concluded that the COAG trial emphasizes the importance of performing large randomized trials for additional pharmacogenetic approaches, particularly for high-risk medications such as warfarin.

Source: Kimmel SE, French B, Kasner SE, et al. A pharmacogenetic versus a clinical algorithm for warfarin dosing. NEJM 2013;369:2283-2293.