Efficacy Of Warfarin In Patients Research Articles

Dicloxacillin-Warfarin Drug-Drug Interaction - A Register-Based Study and In Vitro Investigations in 3D Spheroid Primary Human Hepatocytes.

Dicloxacillin is used to treat staphylococcal infections and we have previously shown that dicloxacillin is an inducer of cytochrome P450 enzymes (CYPs). Here, we employed a translational approach to investigate the effect of a treatment with dicloxacillin on warfarin efficacy in Danish registries. Furthermore, we assessed dicloxacillin as an inducer of CYPs in vitro. We conducted a register-based study and analyzed international normalized ratio (INR) levels in chronic warfarin users before and after short- and long-term use of dicloxacillin (n=1023) and flucloxacillin (n=123). Induction of CYPs were investigated in a novel liver model of 3D spheroid primary human hepatocytes (PHHs) at the level of mRNA, and protein and enzyme activity. Short- and long-term dicloxacillin treatments decreased INR levels by -0.65 (95% CI: -0.57 to -0.74) and -0.76 (95% CI: -0.50 to -1.02), respectively. More than 90% of individuals experienced subtherapeutic INR levels (below 2) after long-term dicloxacillin treatment. Flucloxacillin decreased INR levels by -0.37 (95% CI: -0.14 to -0.60). In 3D spheroid PHHs, the maximal induction of CYP3A4 mRNA, protein and enzyme activity by dicloxacillin were 4.9-, 2.9- and 2.4-fold, respectively. Dicloxacillin also induced CYP2C9 mRNA by 1.7-fold. Dicloxacillin induces CYP enzymes and reduces the clinical efficacy of warfarin in patients. This effect is substantially exacerbated during long-term treatment with dicloxacillin. The in vitro results corroborated this drug-drug interaction and correlated to the clinical findings. Caution is warranted for warfarin patients that initiate dicloxacillin or flucloxacillin, especially for a long-term treatment of endocarditis.

GW29-e0332 Outcomes of warfarin use in atrial fibrillation patients with end-stage and non-end-stage renal disease: a systematic review and meta-analysis of observational studies

Whether warfarin can bring good outcomes for patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is uncertain. To better answer this question, we performed a meta-analysis to evaluate the safety and efficacy of warfarin in patients with AF and end-stage renal disease (ESRD) and

Safety and efficacy of warfarin in patients with moderate thrombocytopenia

IntroductionPatients with moderate thrombocytopenia and comorbidities requiring anticoagulation are currently sub-optimally treated because of bleeding concerns. Guidance on anticoagulating such patients is currently lacking because of limited data on safety and efficacy of anticoagulation in such patients. MethodsThis retrospective study compared the incidence of bleeding and thrombosis in a cohort of warfarinized patients with sustained platelet counts below 100×109/L against a cohort with normal platelet counts (>140×109/L). Primary outcomes of safety and efficacy were determined by incidence rate ratios (IRR) of bleeding and thrombotic events. International normalized ratio (INR) and platelet counts during adverse events in thrombocytopenic arm were secondary outcomes. Results137 thrombocytopenic patients (104,985 patient-exposure days) were compared against 939 normal patients (715,193 patient-exposure days). IRR of minor, major bleeding and thrombosis among thrombocytopenic patients were 3.03 (95% CI: 1.57–5.60), 1.48 (95% CI: 0.44–3.98), and 0.807 (95% CI: 0.09–3.43) respectively. Median INR and platelet count readings during minor and major bleeds were 3.60 (IQR: 2.70–4.12) and 3.12 (IQR: 2.82–4.22), and 99×109/L (IQR: 77.0–147.0×109/L) and 115×109/L (IQR: 107.5–169.5×109/L) respectively. ConclusionWarfarinized thrombocytopenic patients are at higher risk of minor bleeding complications with a higher tendency for major bleeding but derive similar benefits against thrombotic events compared to normal patients. Bleeding events are associated with higher INRs. A narrow INR target with an upper limit below 2.5 together with closer anticoagulation monitoring may improve safety of patients.

The Role for Anticoagulation with Warfarin in Patients with Systolic Heart Failure and Normal Sinus Rhythm

Objective: To evaluate the role of anticoagulation with warfarin in patients with systolic heart failure (HF) and normal sinus rhythm (NSR). Data Sources: Literature was accessed through MEDLINE (1950–December 2007) and the American College of Cardiology Annual Scientific Session (2004) using the terms heart failure, warfarin, and anticoagulation. Study Selection and Data Extraction: All articles in English identified via the searches were evaluated. We excluded trials that evaluated the use of anticoagulation in patients with atrial fibrillation (AF) or valvular disorders. Data Synthesis: Patients with systolic HF are considered to be in a prothrombotic state. Studies have demonstrated a decreased incidence of thromboembolic events with anticoagulation therapy in patients with HF and concomitant AF, valvular dysfunction, or hypercoagulable disorders, but there are limited data supporting the role of anticoagulation in patients with HF and NSR. There are 3 prospective clinical trials and 1 ongoing trial designed to assess the efficacy of warfarin in patients with HF and NSR. These trials compare warfarin with antiplatelet therapy or no antithrombotic therapy. Warfarin did not show a benefit in the primary clinical composite outcome of death, myocardial infarction, or stroke, but was associated with more adverse events. However, these trials were underpowered to detect a difference between treatment arms. Conclusions: There is no objective evidence to support the need for anticoagulation with warfarin in patients with systolic HF and NSR. Additional large randomized, controlled trials need to be completed to determine the efficacy and safety of anticoagulation with warfarin in such patients.