Direct-acting Oral Anticoagulants In Patients Research Articles

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Significant Tricuspid Regurgitation.

There are limited data on the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation with significant tricuspid regurgitation (TR), which can lead to hepatic dysfunction and intestinal malabsorption. We aimed to compare the efficacy and safety of DOACs and warfarin for patients with atrial fibrillation with significant (moderate to severe) TR. A total of 1215 patients with significant TR and atrial fibrillation who were treated with warfarin (N=491) or DOACs (N=724) were retrospectively analyzed. The primary outcomes were ischemic stroke, systemic embolic events, and hospitalization for major bleeding. The secondary outcomes were intracranial hemorrhage, hospitalization for gastrointestinal bleeding, all-cause mortality, and a composite outcome. The median follow-up duration was 2.4 years. In the inverse probability treatment weighting-adjusted cohort, DOACs and warfarin had a similar risk for ischemic stroke and systemic embolic events (adjusted hazard ratio [aHR], 0.95 [95% CI, 0.67-1.36]; P=0.79) and major bleeding (aHR, 0.78 [95% CI, 0.57-1.06]; P=0.11). For the secondary outcomes, relative to warfarin, DOACs had a lower risk of intracranial hemorrhage and the composite outcome, and a comparable risk for gastrointestinal bleeding and all-cause mortality. In the subgroup analysis, the effects of DOACs on ischemic stroke and systemic embolic events were comparable to the effects ofwarfarin, even in patients with inferior vena cava plethora (increased right atrial pressure) or severe TR. In this study, relative to warfarin, DOACs demonstrated comparable efficacy for ischemic stroke and systemic embolic events and major bleeding, with a lower intracranial hemorrhage risk in patients with significant TR and atrial fibrillation, indicating their effectiveness and safety.

Direct-Acting Oral Anticoagulant Therapy in Cancer Patients-A Review.

Venous thromboembolism (VTE) is an important aspect in cancer patients. There are various pharmacological methods used for thrombotic event treatment. DOACs (direct-acting oral anticoagulants) are gaining popularity among both physicians and researchers and are slowly starting to replace VKAs (vitamin K antagonists), thus becoming a substitute or alternative option for LMWHs (low-molecular-weight heparins). In this article, we present DOACs' main therapeutic advantages and disadvantages in patients with cancer. The only major concern with using DOACs is the higher risk of bleeding; however, there are discrepancies in this matter. There are still some types of cancer for which DOACs are not recommended. Specific cancer types may influence the efficacy of DOAC therapy. Additionally, race and ethnicity may affect therapy in cancer patients with DOACs. A sizeable number of clinical trials are focused on comparing DOACs with other anticoagulants. The current guidelines of different scientific associations are not unanimous in their DOAC assessments. There is still a need for more evidence of DOACs' potential advantages over other methods of anticoagulation in cancer patients to facilitate their position in this recommendation. This literature review presents the current state of knowledge about the use of DOACs in patients with neoplastic growth.

Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Liver Disease

HomeCirculationVol. 147, No. 10Use of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Liver Disease No AccessEditorialRequest AccessFull TextAboutView Full TextView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessEditorialRequest AccessFull TextUse of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Liver Disease Theresa J. Hydes, PhD, Gregory Y.H. Lip, MD and Deirdre A. Lane, PhD Theresa J. HydesTheresa J. Hydes Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, UK (T.J.H., G.Y.H.L., D.A.L.). Liverpool University Hospitals National Health Service Foundation Trust, Aintree University Hospital, Lower Lane, UK (T.J.H.). Search for more papers by this author , Gregory Y.H. LipGregory Y.H. Lip https://orcid.org/0000-0002-7566-1626 Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, UK (T.J.H., G.Y.H.L., D.A.L.). Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, UK (G.Y.H.L., D.A.L.). Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L., D.A.L.). Search for more papers by this author and Deirdre A. LaneDeirdre A. Lane Correspondence to: Deirdre A. Lane, PhD, Liverpool Centre for Cardiovascular Sciences, University of Liverpool, 6 West Derby Street, Liverpool, UK L7 8TX. Email E-mail Address: [email protected] https://orcid.org/0000-0002-5604-9378 Department of Cardiovascular and Metabolic Medicine, Institute of Life Course and Medical Sciences, University of Liverpool, UK (T.J.H., G.Y.H.L., D.A.L.). Liverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, UK (G.Y.H.L., D.A.L.). Department of Clinical Medicine, Aalborg University, Denmark (G.Y.H.L., D.A.L.). Search for more papers by this author Originally published6 Mar 2023https://doi.org/10.1161/CIRCULATIONAHA.122.063195Circulation. 2023;147:795–797This article is a commentary on the followingComparative Effectiveness and Safety of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation and Chronic Liver Disease: A Nationwide Cohort StudyFootnotesThe opinions expressed in this article are not necessarily those of the editors or of the American Heart Association.For Disclosures, see page 797.Circulation is available at www.ahajournals.org/journal/circCorrespondence to: Deirdre A. Lane, PhD, Liverpool Centre for Cardiovascular Sciences, University of Liverpool, 6 West Derby Street, Liverpool, UK L7 8TX. Email [email protected]net

Outcomes with direct-acting oral anticoagulants in patients with a history of bariatric surgery: a retrospective cohort study

<h2>Abstract</h2><h3>Background</h3> Patients who undergo bariatric surgery have major physiologic changes in their gastrointestinal tract, which can theoretically alter drug absorption and pharmacokinetics. This is especially concerning for drugs with a narrow therapeutic index, as small changes in absorption can have significant effects on safety and efficacy. One class of interest is direct-acting oral anticoagulants (DOACs), for which there is a paucity of data in this population. <h3>Objective</h3> To characterize the use of DOACs (apixaban, dabigatran, rivaroxaban) in patients with a history of bariatric surgery and incidence of clotting and bleeding events. <h3>Setting</h3> Public healthcare system/university hospital, United States. <h3>Methods</h3> This retrospective cohort study included adult patients who were prescribed a DOAC for the prophylaxis or treatment of venous thromboembolism or for stroke and systemic embolism prevention in atrial fibrillation between January 2011 and December 2018. <h3>Results</h3> A total of 191 patients with a history of bariatric surgery were included. Clotting events occurred in 11 of 191 patients (5.8%) receiving DOAC therapy, with a calculated clotting rate of 3.9 clots per 100 person-years. Bleeding events occurred in 42 of 191 patients (22%) receiving a DOAC, with a calculated bleeding rate of 17.1 bleeds per 100 person-years. The use of rivaroxaban versus apixaban was associated with a statistically significant increased risk of bleeding in patients with a history of bariatric surgery. <h3>Conclusion</h3> In this retrospective cohort of bariatric surgery patients receiving DOACs, we found clotting rates consistent with expected rates and bleeding rates above expected rates based on historical data. We also found an increased risk of bleeding in rivaroxaban users compared with apixaban users. Careful evaluation of bleeding risks in bariatric surgery patients is encouraged.

Retrospective Analysis of Direct-Acting Oral Anticoagulants (DOACs) Initiation Timing and Outcomes After Thrombolysis in High- and Intermediate-Risk Pulmonary Embolism.

Direct-acting oral anticoagulants (DOACs) are prescribed in the treatment of venous thromboembolism, including pulmonary embolism (PE). Evidence is limited regarding the outcomes and optimal timing of DOACs in patients with intermediate- or high-risk PE treated with thrombolysis. We conducted a retrospective analysis of outcomes among patients with intermediate- and high-risk PE who received thrombolysis, by choice of long-term anticoagulant agent. Outcomes of interest included hospital length of stay (LOS), intensive care unit LOS, bleeding, stroke, readmission, and mortality. Descriptive statistics were used to examine characteristics and outcomes among patients, by anticoagulation group. Patients receiving a DOAC (n = 53) had shorter hospital LOS compared to those in warfarin (n = 39) and enoxaparin (n = 10) groups (mean LOS 3.6, 6.3 and 4.5 days, respectively; P < .0001). This single institution retrospective study suggests DOAC initiation <48 h from thrombolysis may result in shorter hospital LOS compared to DOAC initiation ≥48 h (P < .0001). Further larger studies with more robust research methodology are needed to address this important clinical question.

Challenges and Possible Solutions to Direct-Acting Oral Anticoagulants (DOACs) Dosing in Patients with Extreme Bodyweight and Renal Impairment

This article aims to highlight the dosing issues of direct oral anticoagulants (DOACs) in patients with renal impairment and/or obesity in an attempt to develop solutions employing advanced data-driven techniques. DOACs have become widely accepted by clinicians worldwide because of their superior clinical profiles, more predictable pharmacokinetics, and hence more convenient dosing relative to other anticoagulants. However, the optimal dosing of DOACs in extreme bodyweight patients and patients with renal impairment is difficult to achieve using the conventional dosing approach. The standard dosing approach (fixed-dose) is based on limited data from clinical studies. The existing formulae (models) for determining the appropriate doses for these patient groups leads to suboptimal dosing. This problem of mis-dosing is worsened by the lack of standardized laboratory parameters for monitoring the exposure to DOACs in renal failure and extreme bodyweight patients. Model-informed precision dosing (MIPD) encompasses a range of techniques like machine learning and pharmacometrics modelling, which could uncover key variables and relationships as well as shed more light on the pharmacokinetics and pharmacodynamics of DOACs in patients with extreme bodyweight or renal impairment. Ultimately, this individualized approach-if implemented in clinical practice-could optimise dosing for the DOACs for better safety and efficacy.

Recurrent Venous Thromboembolism with Direct-Acting Oral Anticoagulants and Body Mass Index: A Single Institutional Study

Introduction: Obesity is a known risk factor for development and worsening of venous thromboembolic episodes (VTEs). The 2016 International Society of Thrombosis and Hemostasis (ISTH) guidelines recommend caution using direct-acting oral anticoagulants (DOACs) in patients with morbid obesity (BMI >40 kg/m2 or weight > 120 kg) due to limited clinical efficacy and safety data supporting their use in this population. The ISTH recommends laboratory monitoring and dose adjustment as needed, if DOACs are being used in these patients. Unfortunately, most health systems do not have timely access to these tests, and the laboratory monitoring of DOACs remains a non-validated concept. Although the review of the currently available data does not reveal a significantly higher risk of recurrent VTE when using DOACs in these patients, the data is limited due to their retrospective and non-randomized nature and are thus hypothesis generating. We hypothesize that recurrent VTEs are higher in patients with morbid obesity and sought to investigate the differences in VTE recurrences in these patients when compared to the other patients. Methods: After institutional review board approval, we conducted a retrospective chart review for 1 year period (Jan 1, 2020 - Dec 31, 2020) on all patients >/= 18 years of age who were seen at our institution, who received a DOAC (Apixaban, Rivaroxaban, Edoxaban or Dabigatran). Patients who did not have any documentation of the outcome of interest, and those who were non-compliant with the DOACs were excluded. In the remainder of the cohort, data on BMI and recurrence of VTE after starting DOACs was collected and analyzed. Fisher's exact test was used to compare VTE recurrence in the different BMI groups. VTE recurrence in BMI groups taking the same DOAC was also compared individually. SPSS version 28 was used for statistical analysis. Results: A total of 549 patients were initially collected and reviewed. 15 patients who did not have any documentation regarding VTE recurrence were excluded. 60 patients who were non-compliant with DOACs were excluded as well. The remaining 474 were including in the final study, out of which 288 (60.7%) were female, and 186 (39.3%) were male. Median age was 60, ±24. 400 (84.3%) had BMI <40 kg/m2, and 74 (15.7%) had BMI ≥40 kg/m2. 388 (81.9%) patients were on Apixaban, 6 (1.2%) on Dabigatran, 79 (16.7%) on Rivaroxaban, and 1 (0.2%) on Edoxaban. Recurrence of VTE while on the DOAC was observed in 4 (1%) patients with BMI <40 kg/m2, compared to 3 (4.1%) patients with ≥40 kg/m2 (p=0.080). Among those taking Apixaban, 3 (0.9%) patients with BMI <40 kg/m2 had recurrence, compared to 2 (3.4%) with ≥40 kg/m2 (p=0.16). For those on Rivaroxaban, 1 (1.6%) patient with BMI <40 kg/m2 had recurrence, compared to 1 (6.7%) patient with ≥40 kg/m2 (p=0.346). No recurrences were observed in patients on Dabigatran and Edoxaban. [Table 1] Conclusions: There was a numerically higher but statistically insignificant increased risk of recurrent VTE while on a DOAC in patients with BMI ≥40 kg/m2 compared to those with BMI <40 kg/m2 (4.1% vs 1%). This increased risk was similar with comparison of individual DOACs as well (3.4% vs 0.9% in the Apixaban group; 6.7% vs 1.6% in the Rivaroxaban group). Our study did not achieve statistical significance to prove our hypothesis, possibly because the analysis was underpowered. Further prospective studies with a larger sample size are needed to establish the safety of DOACs in morbidly obese patients. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Retrospective Comparison of Patients ≥ 80 Years With Atrial Fibrillation Prescribed Either an FDA-Approved Reduced or Full Dose Direct-Acting Oral Anticoagulant

Direct-acting oral anticoagulants (DOACs) represent the standard for preventing stroke and systemic embolization (SSE) in patients with atrial fibrillation (AF). There is limited information for patients ≥ 80 years. We report a retrospective analysis of AF patients ≥ 80 years prescribed either a US Food and Drug Administration (FDA)-approved reduced (n = 514) or full dose (n = 199) DOAC (Dabigatran, Rivaroxaban, or Apixaban) between January 1st, 2011 (first DOAC commercially available) and May 31st, 2017. The following multivariable differences in baseline characteristics were identified: patients prescribed a reduced dose DOAC were older (p < 0.001), had worse renal function (p = 0.001), were more often prescribed aspirin (p = 0.004) or aspirin and clopidogrel (p < 0.001), and more often had new-onset AF (p = 0.001). SSE and central nervous system (CNS) bleed rates were low and not different (1.02 vs 0 %/yr and 1.45 vs 0.44 %/yr) for the reduced and full dose groups, respectively. For non-CNS bleeds, rates were 10.89 vs 4.15 %/yr (p < 0.001, univariable) for the reduced and full doses, respectively. The mortality rate was 6.24 vs 1.75 %/yr (p = 0.001, univariable) for the reduced and full doses. Unlike the non-CNS bleed rate, mortality rate differences remained significant when adjusted for baseline characteristics. Thus, DOACs in patients ≥ 80 with AF effectively reduce SSE with a low risk of CNS bleeding, independent of DOAC dose. The higher non-CNS bleed rate and not the mortality rate is explained by the higher risk baseline characteristics in the reduced DOAC dose group. Further investigation of the etiology of non-CNS bleeds and mortality is warranted.

Direct-acting oral anticoagulants in patients with atrial fibrillation and valvular heart disease.

Direct-acting oral anticoagulants (DOACs) are an effective alternative to warfarin for patients with atrial fibrillation (AF) who require thromboembolic risk reduction. This article discusses the newly acceptable use of DOACs in patients with valvular AF, including native valvular heart disease and patients with bioprosthetic valves.

50P Direct-acting oral anticoagulants prescribing pattern in patients with gynaecological cancer: Results of a survey among Italian oncologists belonging to MITO group and AIOM society

50P Direct-acting oral anticoagulants prescribing pattern in patients with gynaecological cancer: Results of a survey among Italian oncologists belonging to MITO group and AIOM society

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients With Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis.

The association of patient and prescriber characteristics with use of warfarin versus direct-acting oral anticoagulants (DOACs) in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) is not well studied. The 20% Centers for Medicare & Medicaid Services Parts A, B, and D claims data from 2010 to 2017 were used to identify patients with stage 3, 4, or 5 CKD and AF who received a DOAC (apixaban, dabigatran, rivaroxaban) or warfarin. Prescribers were categorized as cardiologists, primary care providers (PCPs), and others. Using logistic regression, we estimated odds ratios (ORs) for the association of baseline characteristics and prescriber specialty with first use of a DOAC, relative to warfarin. We identified 22,739 individuals with CKD who were newly initiated on oral anticoagulation for AF. New DOAC prescriptions increased from 490 in 2011 to 3261 in 2017, and displaced warfarin over time (1849, 2011; 945, 2017). By Q4 of 2014, cardiologists prescribed DOACs as initial treatment more frequently than warfarin, but non-cardiologists did not do so until 2015. As of 2017, apixaban was the most widely prescribed anticoagulant, comprising 56% and 50% of prescriptions by cardiologists and non-cardiologists, respectively. PCPs (OR 0.54, 0.51-0.58) and other providers (OR 0.55, 0.51-0.59) were less likely than cardiologists to prescribe DOACs. DOAC prescriptions, particularly apixaban, increased over time and gradually displaced warfarin. The total number of patients with AF and CKD receiving anticoagulation increased over time. Cardiologists increased DOAC prescriptions more rapidly than non-cardiologists.

DOACs in Mechanical and Bioprosthetic Heart Valves: A Narrative Review of Emerging Data and Future Directions.

In the recent years, there has been significant transformation in the management of valvular heart disease (VHD), as a result of new minimally invasive technologies, such as the transcatheter aortic valve implantation (TAVI). Conventionally, mechanical heart valves require anticoagulation with warfarin to prevent thrombogenic events. Lately, there has been an uptrend in the usage of direct-acting oral anticoagulants (DOACs) in both mechanical and bioprosthetic heart valves. In clinical practice, there has shown to be notable heterogeneity in the antithrombotic regimen for patients. Recommendations from clinical guidelines and emerging data on DOAC use in these settings will be critically reviewed here. Future large, randomized-controlled trials are warranted to delineate the role of DOACs in patients receiving a bioprosthetic valve/TAVI or mechanical heart valve, with and without a baseline indication for anticoagulation or antiplatelets. Until clinical trial data from well-designed studies are available, providers must remain vigilant about DOAC use in patients with VHD, especially in patients with a bioprosthetic or mechanical heart valve.

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis

Prescribing Patterns of Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease: A Retrospective Cohort Analysis

Measurement of Anticoagulation in Patients on Dabigatran, Rivaroxaban, and Apixaban Therapy by Novel Automated Thrombelastography.

Background Direct-acting oral anticoagulants (DOACs) do not require monitoring. Measurement of DOAC effect would be useful in the event of bleeding, trauma, and thromboembolism while on anticoagulation. We evaluated the effectiveness of the investigational DOAC assays on the TEG®6s Hemostasis Analyzer to assess the anticoagulant effect of DOACs in patients treated for atrial fibrillation or deep vein thrombosis (DVT). Methods Patients on treatment for a minimum of 7 days with standard doses of dabigatran, rivaroxaban, and apixaban were included. DOAC plasma concentrations and TEG®6s Reaction (R)-time were measured and correlated. The sensitivity, specificity, and negative predictive value (NPV) of R-time to detect DOAC concentrations of ≥30, ≥50, and ≥100 ng/mL were calculated. Results A total of 189 patients were included, ( n = 50) on apixaban, ( n = 62) on rivaroxaban, ( n = 53) on dabigatran, and ( n = 24) on no DOAC were studied. Using the direct thrombin inhibitor (DTI) channel, R-time demonstrated strong linear correlation with dabigatran levels (r = 0.93, p < 0.0001). Using the antifactor Xa (AFXa) channel, R-time demonstrated strong nonlinear correlation with rivaroxaban and apixaban levels ( r s = 0.92 and 0.84, respectively, p < 0.0001 for both). R-time revealed strong sensitivity and NPV in detecting low DOAC levels for the predefined concentrations. Conclusion R-time measured by TEG®6s DOAC-specific cartridge has a strong correlation with concentrations of the most commonly used DOACs with high sensitivity and NPV for detecting lower drug levels that are considered clinically relevant for patients in need of antidote, or prior to urgent surgery. Further studies to determine the relation of R-time to clinical outcomes are warranted.

Usage of Direct Acting Oral Anticoagulants in Cirrhotic and Non-Cirrhotic Portal Vein Thrombosis: A Systematic Review.

Thrombosis of the portal vein (PVT) is generally seen in the setting of liver cirrhosis and to a lesser extent in the absence of cirrhosis. There is no clear guidance in relation to approaching treatment with anticoagulation in this condition. The professional societies and guidelines recommend treatment with traditional anticoagulation like low-molecular-weight heparin and vitamin-K antagonists in patients presenting with acute portal vein thrombosis. There is no clarity in relation to treatment in the setting of chronic PVT and in patients with cirrhosis. Also, the role of direct-acting oral anticoagulants (DOACs) that are becoming a preferred choice for anticoagulation for various other indications is not clear in the case of PVT. There are a very few studies in the medical literature that have investigated the role of DOACs in patients with PVT in different settings. Thus, we performed a systematic review of the literature to study the use of DOACs in PVT in patients with and without cirrhosis. The results of the available studies show that DOACS appears to be a promising choice for the treatment of patients with PVT. The availability of more data in the future along with better availability of the approved reversal agents for various DOACs is expected to make DOACS a preferred choice for the clinicians to treat patients with PVT.

Treatment of direct oral anticoagulants in patients with liver cirrhosis and portal vein thrombosis.

Although patients with cirrhosis are known to be in a state of “rebalance” in that pro- and anticoagulant factors increase the risk for both bleeding and thrombosis, the prevalence of portal vein thrombosis (PVT) in patients with cirrhosis can be up to 26%. Therefore, physicians should consider anticoagulation for the prevention and management of PVT in patients with cirrhosis who are at high risk of PVT. Vitamin K antagonist or low molecular weight heparin is suggested as the standard treatment for PVT in cirrhosis. With the advent of new direct-acting oral anticoagulants (DOACs), there is a paradigm shift of switching to DOACs for the treatment of PVT in patients with cirrhosis. However, the safety and efficacy of DOACs in the treatment of PVT was not well-known in patients with cirrhosis. Therefore, this review focused on the current knowledge about the efficacy, safety concerns, and hepatic metabolism of DOACs in patients with cirrhosis and PVT.

Five-Year Trends in Potential Drug Interactions with Direct-Acting Oral Anticoagulants in Patients with Atrial Fibrillation: An Australian-Wide Study.

Background: Co-prescribing medications that can interact with direct-acting oral anticoagulants (DOACs) may decrease their safety and efficacy. The aim of this study was to examine the co-prescribing of such medications with DOACs using the Australian national general practice dataset, MedicineInsight, over a five-year period. Methods: We performed five sequential cross-sectional analyses in patients with atrial fibrillation (AF) and a recorded DOAC prescription. Patients were defined as having a drug interaction if they had a recorded prescription of an interacting medication while they had had a recorded prescription of DOAC in the previous six months. The sample size for the cross-sectional analyses ranged from 5333 in 2014 to 19,196 in 2018. Results: The proportion of patients who had potential drug interactions with a DOAC decreased from 45.9% (95% confidence interval (CI) 44.6%–47.4%) in 2014 to 39.9% (95% CI 39.2%–40.6%) in 2018, p for trend < 0.001. During this period, the most frequent interacting class of medication recorded as having been prescribed with DOACs was selective serotonin/serotonin and norepinephrine reuptake inhibitor (SSRI/SNRI) antidepressants, followed by non-steroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers (CCBs) and amiodarone. Conclusions: Overall, potential drug interactions with DOACs have decreased slightly over the last five years; however, the rate of possible interaction with SSRIs/SNRIs has remained relatively unchanged and warrants awareness-raising amongst prescribers.

Direct Oral Anticoagulants in Obesity: An Updated Literature Review

To review literature on the use of direct-acting oral anticoagulants (DOACs) in patients with high body weight (BW) and/or high body mass index (BMI) and to make recommendations regarding use in this patient population. A search using PubMed was conducted (inception to April 13, 2020) using the term DOAC AND the terms obesity OR body weight. A separate search was also conducted with individual DOACs (dabigatran, apixaban, rivaroxaban, edoxaban) and the aforementioned terms. Studies included examined the effect of BW and/or BMI on DOAC pharmacokinetics, efficacy, or safety. Included studies had DOAC indications of prevention of stroke in nonvalvular atrial fibrillation, or treatment or long-term prevention of venous thromboembolism. The efficacy and safety of DOACs in patients with high BW/BMI has not yet been elucidated by randomized trials; however, 2016 international guidelines suggest avoiding their use in patients with a BW >120 kg or BMI >40 kg/m2. Since 2016, several studies have been published examining use of DOACs in this patient population. This review thoroughly discusses the literature on DOACs in patients with a BW >120 kg or BMI >40 kg/m2 pre-2016 and post-2016 guidelines. Evidence indicates that each DOAC may have differences in outcomes when used in patients with a high BW/BMI. Currently, low-quality data are available that support avoiding dabigatran and considering apixaban or rivaroxaban; lack of sufficient data preclude a recommendation for edoxaban use in this patient population.

Direct-acting oral anticoagulant use at extremes of body weight: Literature review and recommendations

To review the literature on treatment of venous thromboembolism (VTE) and prevention of cardioembolic stroke with direct-acting oral anticoagulants (DOACs) in low- and high-body-weight patients and to make recommendations regarding agent selection and dosing in these patient populations. The selection and optimal dosing of DOACs in low- and high-body-weight patients has not yet been fully elucidated by clinical trials; however, evidence suggests that issues of both safety and efficacy in patients at the extremes of body weight may warrant careful consideration when selecting a DOAC for such patients. This review provides a thorough discussion of the use of DOACs in the treatment of VTE and prevention of cardioembolic stroke in patients at the extremes of body weight and provides guidance regarding agent selection. While the published evidence on use of DOACs in patients at extremes of body weight is sparse, apixaban and rivaroxaban appear to have the most favorable safety and efficacy profiles. Edoxaban and dabigatran should be avoided.

Direct-Acting Oral Anticoagulants in Atrial Fibrillation: What's New in the Literature.

Atrial fibrillation (AF) is considered the most common sustained cardiac arrhythmia, and it is associated with a significant risk of adverse events, especially ischemic stroke. Oral anticoagulation is the cornerstone for stroke prevention in AF; for many years, only vitamin K antagonists were used for this purpose, with an absolute risk reduction >60%. However, these agents have limitations, such as narrow therapeutic margins and drug-food and drug-drug interactions. More recently, 4 direct-acting oral anticoagulants (DOACs)-non-vitamin K antagonists-have become available for patients with AF: dabigatran, rivaroxaban, apixaban, and edoxaban. In addition to a comparable efficacy to warfarin in large randomized controlled trials, DOACs were found to promote a lower risk of intracranial bleeding. The strategic dosage and lack of need for periodic prothrombin-time testing make their use attractive, especially for primary or secondary prevention of stroke in older adults. Furthermore, among patients with AF presenting with acute coronary syndrome or undergoing percutaneous coronary intervention, apixaban is associated with a reduction in serious bleeding events when compared with warfarin. On the other hand, there is no evidence of benefit of DOACs in patients with mechanical prosthetic valves or moderate/severe mitral stenosis. Furthermore, the suitability of DOACs in patients with liver disease is still poorly understood, and their safety in patients requiring renal replacement therapy remains uncertain. This review provides an overview of the main trials of DOACs, their pharmacology and safety profile, clinical implications, and best indications in light of the current evidence.