Warfarin pharmacogenetics: a controlled dose-response study in healthy subjects.

The aim of this study was to determine how genetic variants contribute to warfarin dosing variability when non-genetic factors are controlled. Thirty healthy subjects were subjected to a warfarin dosing algorithm with daily international normalized ratio (INR) measurements to INR ≥ 2.0, then off warfarin to INR ≤ 1.

Comparative performance of gene-based warfarin dosing algorithms in a multiethnic population.

Summary Background: Gene-based warfarin dosing algorithms have largely been developed in homogeneous populations, and their generalizability has not been established.

Objectives: We sought to assess the performance of published algorithms in a racially diverse and multiethnic sample, and determine if additional clinical variables or genetic variants associated with dose could enhance algorithm performance.

Patients And Methods: In 145 compliant patients on warfarin with a goal international normalized ratio (INR) of 2-3, stable, therapeutic doses were compared with predicted doses using 12 reported algorithms that incorporated CYP2C9 and VKORC1 variants.

Stroke prevention in atrial fibrillation.

Atrial fibrillation (AF) is a risk factor for ischemic stroke. In randomized trials, AF raised the risk of stroke nearly sixfold, cumulating in a 35% risk over a lifetime. Anticoagulation with warfarin reduces the danger of ischemic stroke, but carries hemorrhagic risks, making this agent unsuitable for treating many patients.

Indications, management, and patient education: anticoagulation therapy during pregnancy.

Anticoagulation is necessary in a variety of cardiovascular diseases to prevent thromboembolic complications. On a chronic basis, this type of therapy carries with it frustrations and challenges to both the woman and the health care provider related to monitoring, safety, and compliance. These problems are compounded during pregnancy by specific pharmacological considerations that often require substitution of a parenteral agent.

Noninvasive evaluation of the extracranial carotid arteries in patients with cerebrovascular events and atrial fibrillations.

Noninvasive carotid artery testing was performed in 73 patients with nonvalvular atrial fibrillation who were referred because of symptoms or signs of cerebrovascular disease. Thromboembolism related to atrial fibrillation without valvular heart disease was the probable source of cerebral ischemia in 25 (80%) of 31 patients with stroke and coexisting atherosclerotic disease at the carotid artery bifurcation in six (20%). Nonvalvular atrial fibrillation was the probable source of symptoms in nine (70%) of 13 of patients with transient cerebral ischemia, while coexisting carotid artery disease was present in four (30%).