New antithrombotic drugs: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).
ABSTRACT This chapter focuses on new antithrombotic drugs that are in phase II or III clinical testing. Development of these new agents was prompted by limitations of existing antiplatelet, anticoagulant, or fibrinolytic drugs. Addressing these unmet needs, this chapter (1) outlines the rationale for development of new antithrombotic agents, (2) describes the new antiplatelet, anticoagulant, and fibrinolytic drugs, and (3) provides clinical perspectives on the opportunities and challenges faced by these novel agents.
SourceAvailable from: Roger M Mills[Show abstract] [Hide abstract]
ABSTRACT: Background: Many individuals with atrial fibrilla-tion (AF) do not receive recommended anticoagu-lant prophylaxis for stroke prevention. The study in-vestigators attempted to assess whether the presence of relative contraindications (RCIs) to anticoagula-tion with warfarin might contribute to this, and to assess the risks and benefits of prophylaxis in pati-ents with RCIs. Methods: Study investigators iden-tified patients with established non-valvular AF and flutter in a claims database. Operationally defined RCIs included, in order of clinical severity: (1) prior intracranial hemorrhage; (2) gastrointestinal bleed-ing or esophageal varices; (3) neurological disorder; and (4) dizziness. Nonfatal events were attributed to warfarin if patients had an appropriate claim in the previous month. Results: A total of 67,082 AF patients were eligible for analysis, including 50,485 (75.3%) in the prevalent cohort. Warfarin exposure during the study period was 68% in the prevalent cohort. At ba-seline, 50.5% of prevalent cohort patients had one or more RCIs. Patients with RCI had higher preva-lence of stroke risk factors (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, and prior stroke or transient ischemic attack) compared to those without RCI. Patients with RCIs often re-ceived warfarin and had lower rates of ischemic stro-ke than those who did not. Conclusions: These results suggest that RCIs do not account for underutilization of anticoagulant prophylaxis in AF patients. Further, the benefit/risk aspects of anticoagulation for stroke prophylaxis may be favorable for many patients with RCIs.
[Show abstract] [Hide abstract]
ABSTRACT: Background and Objectives The effects of age and sex on apixaban pharmacokinetics and pharmacodynamics were studied. Methods This was an open-label, single-dose, 2 × 2 factorial study. Healthy young (aged 18–40 years) and elderly (aged ≥65 years) male and female subjects received a single oral 20 mg dose of apixaban. Blood and urine samples were collected for pharmacokinetic and pharmacodynamic (blood only) analyses. Subjects were monitored for adverse events throughout the study. Results Seventy-nine subjects were enrolled into four groups: young males (n = 20), elderly males (n = 20), young females (n = 20) and elderly females (n = 19). Age did not affect the maximum observed plasma concentration (C max). The mean area under the concentration–time curve from time zero extrapolated to infinite time (AUC∞) was 32 % greater in elderly subjects than in young subjects. The mean C max and AUC∞ values were 18 and 15 % higher, respectively, in females than in males. The time course of the mean international normalized ratio (INR), modified prothrombin time (mPT) and anti-Xa activity tracked the apixaban concentration–time curve. All three pharmacodynamic measures exhibited a positive linear correlation with the plasma apixaban concentration. Differences in the mean INR, mPT and anti-Xa activity between age and sex groups were small ( Conclusion There were no clinically meaningful age- or sex-related differences in the pharmacokinetics and pharmacodynamics of apixaban that would require dose modification on the basis of age or sex alone.Clinical Pharmacokinetics 01/2015; DOI:10.1007/s40262-014-0228-0 · 5.49 Impact Factor