Use Of Direct Oral Anticoagulants In Patients Research Articles

Direct Oral Anticoagulant Use in Valvular Heart Disease

Direct oral anticoagulants (DOACs) are indicated by the European Medicines Agency and US Food and Drug Administration for stroke prevention in patients with nonvalvular atrial fibrillation (AF). The role of DOACs in patients with AF and concomitant valvular heart disease (VHD) is less clear. Recent subanalyses of randomized controlled trials and meta-analyses have evaluated the role of DOACs in patients with AF and VHD. Patients with native aortic valve disease, tricuspid valve disease, or mitral regurgitation will be the primary focus as these represent the majority of VHD represented in the DOAC AF trials. Limited data exist on the role in patients with rheumatic mitral stenosis, mechanical heart valves, and mitral valve repair. This review provides the current clinical and scientific data pertaining to the safety and efficacy of DOAC use in patients with VHD.

Use of direct oral anticoagulants for the prevention and treatment of thromboembolic disease in patients with reduced renal function: a short review of the clinical evidence.

BackgroundThe use of direct oral anticoagulants (DOACs) is restricted by the limitations of clinical trials guiding therapy for patients with renal impairment, as many of these trials excluded patients with severe renal impairment. There are currently four agents available: dabigatran, rivaroxaban, apixaban, and edoxaban. The purpose of this review was to 1) describe current recommended dosing for each DOAC and published postmarketing data, including case reports, on the use of these agents in the renally impaired; and 2) discuss patient adherence and satisfaction and the cost of these agents.Materials and methodsA literature search was conducted using Medline and Embase with the terms “dabigatran” or “rivaroxaban” or “apixaban” or “edoxaban” and “renal impairment”. Clinical trials and case reports describing the use of DOAC therapy in patients with renal impairment were reviewed. A second search was conducted to find articles evaluating patient adherence, patient satisfaction, and pharmacoeconomics of DOACs.ResultsThere are a multitude of subgroup and post hoc analyses, as well as six case reports with dabigatran and one case report with apixaban, that provide insight for the clinical use of DOACs in patients with renal impairment. Dabigatran exhibits the greatest level of renal elimination, and there are data from clinical trials and several case reports that warrant reconsideration before use. Other DOACs may be a better option in patients with impaired renal function. Further, data from patient-adherence studies have suggested that DOACs that are dosed daily (rather than twice daily) are optimal and preferred. There does not appear to be a cost difference between DOACs and warfarin therapy.ConclusionDOAC therapy in patients with impaired renal function requires more critical review of study data, as these patients may have increased risk of bleeding. It is also valuable to consider patient preferences and cost when selecting the appropriate option for oral anticoagulation.

Use of Direct Oral Anticoagulants in Patients on Immunomodulatory Agents

The risk of venous thromboembolism (VTE) is increased in individuals with cancer, particularly in those with multiple myeloma. The immunomodulatory agents (IMiDs) thalidomide, lenalidomide and pomalidomide are commonly used to treat multiple myeloma and other hematologic malignancies and are associated with increased risk of VTE. Current National Comprehensive Cancer Network (NCCN) guidelines (v.1.2016) on cancer-associated VTE utilize a risk assessment model based on a few small studies to guide VTE prophylaxis for multiple myeloma patients being treated with an IMiD (Palumbo, et al. Leukemia, 2008). Aspirin is recommended for lower risk patients while prophylactic-dose low molecular weight heparin or therapeutic warfarin are recommended for higher risk patients.The use of direct oral anticoagulants (DOACs) for cancer-associated VTE is currently under investigation (Raskob, et al. Lancet Haematol, 2016). Little is known about their role in VTE prophylaxis in patients on IMiDs. The purpose of this study was to explore the use of DOACs in patients receiving IMiDs. We performed a retrospective chart review of all patients at the University of Virginia Health System who received an IMiD and who were taking either a DOAC or warfarin between January 1, 2010 and December 31, 2015. DOACs included dabigatran, rivaroxaban, and apixaban. IMiDs included lenalidomide, thalidomide, and pomalidomide. The primary endpoint was to assess the safety of DOACs as compared to warfarin, and the secondary endpoint was to assess their efficacy.We collected baseline patient information, as well as diagnosis, IMiD, anticoagulant, antiplatelet agent and dose, duration of treatment, concurrent antineoplastic therapies, and thrombotic risk factors. We utilized the NCCN definitions of individual and myeloma-related thrombotic risk factors. Many patients had changes in their IMiD or anticoagulation. Thus, separate encounters were collected, where an encounter was the combination of an IMiD agent and dose, the anticoagulant, the antiplatelet agent (if any), and the thrombotic risk profile for that time period. Descriptive analyses were performed on all encounters in both groups. Rates of bleeding and thrombotic events were calculated.There were 21 discrete patients in the DOAC group and 16 in the warfarin group. Characteristics and outcomes are described in Table 1. There were four non-major bleeding events in the DOAC group; two of the four bleeding events occurred while on concomitant aspirin therapy. The patient with hematuria stopped anticoagulation and cystoscopy revealed bladder cancer. The other patients did not change or stop therapy. There were six bleeding events in the warfarin group: two were major and four were non-major. The two major events were gastrointestinal bleeding (GIB) and a subarachnoid hemorrhage (SAH). Neither event occurred while on concomitant antiplatelet therapy. The GIB required cessation of therapy, hospitalization, and transfusions. The INR at the time is unknown. The SAH was preceded by a fall while INR was in therapeutic range. Both major and two of the non-major bleeding events occurred in the same patient at different time points and accounted for most of the warfarin-related bleeding events. There was one thrombotic event in the DOAC group. The patient had a non-ST segment elevation myocardial infarction (NSTEMI) while on prophylactic-dose rivaroxaban. She was not on concomitant antiplatelet therapy. Arterial thrombotic events are not typically seen with IMiDs, and the NSTEMI was thought to be related to the recent initiation of carfilzomib. There were no thrombotic events in the warfarin group.This was a retrospective, single-institution study assessing the safety and efficacy of DOACs as compared to warfarin in patients on IMiDs. In our study, all bleeding events in the DOAC group were non-major, while patients on warfarin experienced both major and non-major bleeds. Only one thrombotic event was recorded in the DOAC group. DOACs may represent an attractive alternative to warfarin for VTE prophylaxis in these patients, given no need for routine monitoring and fewer dietary restrictions. Prospective studies in this population are warranted. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Direct Oral Anticoagulants in Cirrhosis Patients Pose Similar Risks of Bleeding When Compared to Traditional Anticoagulation.

Direct oral anticoagulants (DOAC) are important new anticoagulant therapies that are not well studied in patients with chronic liver disease. The aim of this study was to compare rates of bleeding in cirrhosis patients treated with DOAC (factor Xa inhibitors: rivaroxaban and apixaban) to those in cirrhosis patients treated with traditional anticoagulation (warfarin and low molecular weight heparin). We identified a total of 39 patients with cirrhosis who received anticoagulation therapy over a 3-year period (20 DOAC and 19 traditional anticoagulation) from a research database. Medical records were reviewed to obtain clinical data to compare between the groups. Clinical characteristics between the two groups were similar. There were three documented bleeding events in the traditional anticoagulation group and four bleeding events in the DOAC group (p=0.9). There were two major bleeding events in the traditional anticoagulation group and one major bleeding event in the DOAC group. There were no documented reports of drug-induced liver injury during this study period. Among all patients, no significant predictors of bleeding were identified using univariate regression and Cox proportional hazard modeling. This is the first clinical study evaluating the use of DOAC in patients with cirrhosis. DOAC display similar safety characteristics when compared to traditional anticoagulation in patients with cirrhosis and are potentially attractive agents for anticoagulation therapy. Larger studies are now needed to better understand the safety and efficacy of these agents in cirrhosis.