Safety Of Direct Oral Anticoagulants In Patients Research Articles

Safety of DOACs in patients with Child-Pugh Class C cirrhosis and trial fibrillation.

Anticoagulation (AC) is used for stroke prevention in atrial fibrillation (AF). Direct Oral Anticoagulants (DOACs) are safe in patients with AF without cirrhosis, they are hardly studied in patients with advanced cirrhosis. Our study evaluates the safety and outcomes of DOACs in patients with Child-Pugh class C cirrhosis (CPC). We queried TriNetX Database. Patients with CPC and AF were divided into three cohorts: patients on DOACs, no AC, and warfarin. Three study arms were created using a 1:1 propensity score matching system (PSM). Totally 16 029 patients met the inclusion criteria. Of those, 20.2% (n = 3235) were on DOACs, 47.1% (n = 7552) were not on AC, and 32.7% (n = 5242) were on warfarin. First arm comparing AC versus no AC, a statistically significant benefit was identified in 3-year mortality risk (47% vs 71%, P < 0.0001) and transplant status (17% vs 5%, p < 0.0001) with AC. However, no significant difference was identified regarding intracranial hemorrhage and GI bleeding risk. Second arm comparing patients on DOACs versus no AC, we identified mortality benefit (40% vs 72%, P < 0.0001) and a higher transplant rate (9% vs 3.2%, P < 0.0001) with DOACs. Intracranial hemorrhage rates (6% vs 4%, P = 0.03) were higher in patients on DOACs. Third arm comparing patients on DOACs versus Warfarin, a statistically significant lower risk of intracranial hemorrhage (6.6% vs 8.7%, P = 0.004) and GI bleed (2% vs 2.4%, P < 0.0001) were identified in patients on DOACs. Anticoagulation is safe in patients with CPC with AF and may provide a mortality benefit. DOACs are a safer alternative to warfarin.

Tolerability of Direct Oral Anticoagulants and Low Molecular Weight Heparin in Patients with Brain Tumors or CNS Metastases

Background: Despite the increase in the use of direct oral anticoagulants (DOACs) for cancer-associated thrombosis, limited data exists regarding the safety of DOACs in patients with brain metastases or primary brain tumors. The purpose of this retrospective cohort study is to describe overall tolerability of DOACs compared to low-molecular weight heparin (LMWH) for the treatment of venous thromboembolism (VTE) or for stroke prevention in atrial fibrillation (AF), in patients with brain tumors or CNS metastases. Methods: This is a single center, institutional review board approved retrospective cohort study at New York University Langone Health of patients with primary brain tumors or CNS metastasis that received therapeutic dosed anticoagulation with either a DOAC or LMWH (enoxaparin) between December 1, 2018 and August 19, 2022. Electronic medical records were reviewed for pertinent data. The primary outcome was tolerability of anticoagulation, which included continuation of initial anticoagulation therapy and absence of any switches in anticoagulation, dose adjustments or temporary interruptions. Reasons for discontinuations included bleeding events, intolerance/patient preference (such as the need for subcutaneous administration or cost of therapy), provider preference, or a change in clinical status such as transition to hospice or unable to determine based on chart review. Secondary outcomes included the incidence of anticoagulation discontinuations secondary to an intracerebral hemorrhage (ICH). Results: A total of 153 patients were included (DOAC n = 105, 69%; enoxaparin n = 48, 31%). The study population was predominantly White (74%), male (59%), with a median BMI≥30 kg/m2 in 40% of the cohort and age of 65 (IQR 56-73) years; however, the enoxaparin group was younger than the DOAC group at 59.5 years vs. 67 years (p &amp;lt;0.001), respectively at the time of anticoagulation initiation. Primary brain tumors were the most prevalent in the total cohort at 89%, with enoxaparin most commonly prescribed at 71% versus a DOAC at 47%, p = 0.005. Other primary malignancies included anaplastic astrocytoma, glioma, anaplastic oligodendroglioma, and tanycytic ependymoma. Non-small cell lung cancer was the most common malignancy that resulted in CNS metastasis (7.2%). The most common indication for anticoagulation was for the treatment of VTE at 70%, followed by stroke prevention in AF at 28%, with the remainder 2% as off-label. The primary outcome of remaining on initial anticoagulant chosen without any anticoagulant therapy changes occurred in only 52% of the cohort. There were more changes in therapy in the enoxaparin cohort at 29, 60% vs. 44, 42% for the DOAC cohort, p = 0.033, driven by provider preference in 48% of the cohort and patient intolerance in 29% of the cohort. More patients in the enoxaparin cohort were switched to a DOAC (n = 17) and more patients in the DOAC cohort had their initial anticoagulation discontinued for non- ICH reasons (n = 14). The median time to any anticoagulation switch was 2.12 months (IQR 0.35-4.27 months). Discontinuations in patients who were still alive was primarily driven by completion of therapy, deemed by the treatment team, intolerance or patient preference, and provider preference (Table 1). Though the reason for provider preference was not always clearly elucidated upon chart review, this trend supports the movement towards increasing DOAC use. The secondary outcome of the incidence of ICH was also lower in the DOAC cohort compared to enoxaparin at 3.8 vs 14.6% (p = 0.037). (Figure 1) Conclusions: Our study demonstrates real world prescribing practice of anticoagulants for the treatment of VTE or stroke prevention in AF in patients with primary brain tumors or metastases. Although initial anticoagulants chosen were either discontinued or switched to an alternative agent, we observed a shift towards a preference for DOACs, similar to the shift towards DOACs for cancer associated thrombosis. We also observed a lower incidence of ICH with DOACs compared to LMWH. However, these results should be confirmed in a randomized controlled trial to account for the inherent selection biases we could not account for, which may have favored the initial anticoagulant chosen, the reason for switch, and overall tolerability.

Direct oral anticoagulants for the treatment of atrial fibrillation in patients with hematologic malignancies.

Atrial fibrillation (AF) is common in patients with cancer due to both the proinflammatory effect of neoplastic cells and to cardiotoxicity of anti-tumor therapies. Anticoagulation is still challenging in cancer patients due to increased bleeding risk related to specific neoplasms such us hematologic malignancies. The aim of this retrospective study was to evaluate the safety and the efficacy of direct oral anticoagulants (DOACs) in AF patients affected by hematologic neoplasms. We included 97 patients on active anticancer treatment. The median follow-up was 25 months (range 10-108). No thromboembolic complications occurred, while 14 bleeding events were recorded: 1 major, 12 clinical relevant non major bleeding and 1 minor bleeding. Although retrospective and with a small number of enrolled patients, our data support the efficacy and safety of DOACs in patients affected by hematologic malignancies suggesting caution to particular situations, such as thrombocytopenia.

Pocket hematoma after pacemaker or defibrillator surgery: Direct oral anticoagulants versus vitamin K antagonists.

BackgroundDirect oral anticoagulants (DOACs) are the preferred choice of oral anticoagulation in patients with atrial fibrillation (AF). Randomized trials have demonstrated the efficacy and safety of DOAC in patients undergoing a cardiac implantable electronic device procedure (CIED); however, there is limited real-world data.ObjectiveTo evaluate the outcome of patients undergoing an elective CIED procedure in a tertiary referral center with an interrupted DOAC or continued vitamin K antagonist (VKA) regimen.MethodsThis was a retrospective single-center study of consecutive patients with AF undergoing an elective CIED procedure between January 2016 and June 2019. The primary endpoint was a clinically significant pocket hematoma < 30 days after surgery. The secondary endpoint was any systemic thromboembolic complication < 30 days after surgery.ResultsOf a total of 1,033 elective CIED procedures, 283 procedures were performed in patients with AF using oral anticoagulation. One-third of the procedures were performed under DOAC (N = 81, 29%) and the remainder under VKA (N = 202, 71%). The DOAC group was younger, had less chronic renal disease, more paroxysmal AF and a lower HAS-BLED score. The VKA group more often underwent a generator change only in comparison to the DOAC group. Clinically significant pocket hematoma occurred in 5 patients (2.5%) in the VKA group and did not occur in the DOAC group (P = 0.33). There were no thromboembolic events reported.ConclusionIn patients with AF undergoing an elective CIED procedure, the risk of a pocket hematoma and a systemic thromboembolic event is comparably low when using either continued VKA or interrupted DOAC.

Safety and Efficacy of DOACs in Patients with Advanced and End-Stage Renal Disease.

The prevalence of chronic kidney disease (CKD) is increasing due to the aging of the population and multiplication of risk factors, such as hypertension, arteriosclerosis and obesity. Impaired renal function increases both the risk of bleeding and thrombosis. There are two groups of orally administered drugs to prevent thromboembolic events in patients with CKD who require anticoagulation: vitamin K antagonists (VKAs) and direct oral anticoagulants (DOACs). Although VKAs remain the first-line treatment in patients with advanced CKD, treatment with VKAs is challenging due to difficulties in maintaining the appropriate anticoagulation level, tendency to accelerate vascular calcification and faster progression of CKD in patients treated with VKAs. On the other hand, the pleiotropic effect of DOACs, including vascular protection and anti-inflammatory properties along with comparable efficacy and safety of treatment with DOACs, compared to VKAs observed in preliminary reports encourages the use of DOACs in patients with CKD. This review summarizes the available data on the efficacy and safety of DOACs in patients with CKD and provides recommendations regarding the choice of the optimal drug and dosage depending on the CKD stage.

A Multicenter Retrospective Evaluation of Direct Oral Anticoagulants for the Treatment of Heparin-Induced Thrombocytopenia.

Direct oral anticoagulants (DOACs) represent an off-label but potential alternative to traditional therapies for heparin-induced thrombocytopenia (HIT). The objective of this study was to evaluate the efficacy and safety of DOACs in patients with a diagnosis of laboratory-confirmed HIT. A multicenter retrospective cohort study of adult patients with HIT treated with apixaban, rivaroxaban, or dabigatran between 1 January 2013 and 1 January 2020 was performed. Patients with an intermediate or high pre-test probability for HIT and a positive antiplatelet factor 4/heparin complex assay, latex immunoturbidimetric assay, or serotonin release assay were included for analysis. The primary outcome was the composite of newly diagnosed venous or arterial thromboembolism, gangrene, or severe limb ischemia requiring amputation at 3 months following DOAC initiation. This study was approved by local institutional review boards, and the requirement for informed consent was waived. A total of 77 patients from four health systems were included. The median 4Ts score was 5 (interquartile range 4.5-6), and 38 patients (49.4%) had a diagnosis of HIT with thrombosis. The most frequently used DOAC was apixaban (n = 51), followed by rivaroxaban (n = 24) and dabigatran (n = 2). In total, 63 (81.8%) patients received parenteral non-heparin anticoagulation prior to DOAC initiation. Nine patients (11.7%) experienced the primary outcome of HIT-related thrombotic events. Of the 14 patients who exclusively received DOAC therapy, none experienced the primary outcome. Major bleeding occurred in five (6.5%) patients. In this retrospective cohort study, DOACs were associated with rates of thrombotic and hemorrhagic events similar to those with other therapies currently used in the treatment of HIT.

Effectiveness and safety of DOACs for the prevention of recurrent VTE: a prospective cohort study

Abstract Background In the direct oral anticoagulants (DOACs) era, extended anticoagulation after 6–12 months of treatment is an attractive strategy in patients with venous thromboembolism (VTE). Real-life data on the clinical benefit of DOAC over time is lacking. Purpose The aim of this study is to assess the effectiveness and safety of DOACs in patients with acute VTE treated for variable periods. Methods Data on patients with an objective diagnosis of acute VTE treated with DOACs were included in prospective cohort study. Study outcomes were recurrent VTE and major bleeding (ISTH definition). Results Overall, 934 patients were included (mean age 67.0±16.0, male gender 51.4%). Three-hundred and forty-six patients had a deep vein thrombosis (37.0%), 98 (10.5%) had isolated pulmonary embolism and 490 (52.5%) had both. One-hundred and sixty-nine patients (18.1%) had an active cancer, 59 (6.3%) a history of cancer and 365 patients (39.1%) an unprovoked VTE. During DOAC treatment (mean 21.6 months), 7 recurrent VTEs and 25 major bleedings occurred. In 546 and in 98 patients, DOAC was continued with full and reduced doses, respectively. In 290 patients (43.8% unprovoked, 13.8% active cancer, 42.4% associated with non-cancer risk factor), anticoagulants were withdrawn (average treatment duration 8.8 months) and 22 recurrent VTEs occurred over a follow-up off-treatment period of 31.9 months. In these patients, 2 episodes of major bleeding were observed. Overall, 201 patients died; fatal PE occurred in 4 and fatal bleeding in 1 patient. Time course for recurrent VTE according to 2019 ESC risk for recurrence is reported in the Figure. Conclusions In this cohort study, DOACs showed a good risk to benefit profile in the extended phase after an acute VTE event. Funding Acknowledgement Type of funding sources: None. Figure 1. Cumulative incidence of recurrent VTE

Apixaban Is Safe and Effective in Morbidly Obese Patients: A Retrospective Analysis of 390 Patients with BMI ≥40

Background: In patients with venous thromboembolism (VTE), warfarin had been considered standard of care until the new direct oral anticoagulants (DOACs) were developed. Studies in patients with acute VTE and non-valvular atrial fibrillation (AF) have shown comparable therapeutic efficacy and a similar or lower bleeding risk for DOACs when compared to warfarin. However, low representation of obese patients in these studies and the unknown effect of obesity on pharmacokinetics and pharmacodynamics of these drugs have raised questions about efficacy, adequacy of fixed dosing, and safety of DOACs in patients with BMI ≥30 kg/m2. We investigated clinical outcomes of VTE recurrence, stroke and bleeding in morbidly obese patients on apixaban.Method: All adult (age ≥18 years) patients at Montefiore Medical Center with BMI ≥40 who were initiated on anticoagulation with apixaban or warfarin, between March 1, 2013 and March 1, 2017, were identified from electronic medical records using institutional data-mining software. All patients on apixaban were included. Patients on warfarin were selected using a random number generator to match the sample size of the apixaban cohort. Patients with indications for anticoagulation other than AF and prior VTE were excluded. Charts were reviewed to document demographic information and recurrent thrombotic and bleeding events while on anticoagulation during the follow-up period (from the prescription date to the earliest of an event, death or June 30, 2017). Initiation date of anticoagulation was based on the first prescription of warfarin or apixaban. VTE and CVA episodes were confirmed by imaging (compression sonography, ventilation/perfusion scans, CT scans, and MRIs). Bleeding events were classified according to criteria from the Control of Anticoagulation Subcommittee of the International Society on Thrombosis and Haemostasis. Data were analyzed according to anticoagulation indication. Summary statistics and chi-square tests were used to assess statistical significance of the differences in the VTE, CVA and bleeding rates between apixaban and warfarin groups.Results: Data on 390 patients, with a mean age of 61.7 years and a mean BMI of 46.24, were collected. Characteristics of the study population are listed in the table. In the apixaban group, 124 (68.5%) of the patients were on anticoagulation for AF and 58 (32.0%) for VTE; in the warfarin group, the indication for AC was AF in 124 (59.3%) and VTE in 88 (42.1%) of the patients. In patients who were on anticoagulation because of prior VTE, we could not demonstrate a statistically significant difference in the rate of recurrent VTE in apixaban group compared to warfarin group (1.7% vs. 1.1%, OR 1.53, p=0.76). At these recurrence rates, at 80% power with a p<0.05, 6016 morbidly obese patients with VTE and BMIs ≥40 would have been necessary to acquire significance for these data, should they have been significant. Similarly, for patients on anticoagulation for AF, we could not demonstrate a statistically significant difference in the rate of stroke in the apixaban cohort compared to warfarin (0.8% vs. 2.4%, OR 0.33, p=0.31). At these stroke occurrence rates, at 80% power with a p<0.05, 962 morbidly obese patients with AF and BMIs ≥40 would be required to show a decreased rate of stroke in the apixaban group. There was no statistically significant difference in the bleeding rate in the apixaban group (8.3%) vs. those on warfarin (12.0%, OR 0.67, p=0.23), however major bleeding was significantly less common in patients on apixaban (0.6% vs. 4.3%, OR 0.12, p=0.02). Among the 37 patients on apixaban with BMI ≥50 (25 AF, 11 VTE, and 1 with dual indications), one patient with AF had a CVA (4%) and none had recurrent VTE. Among the 46 patients on warfarin with BMI ≥50 (30 AF, 16 VTE), one had a CVA (3.3%) and none had recurrent VTE.Conclusion: This study provides further evidence of comparable efficacy and safety of apixaban and warfarin in patients with AF and VTE. Although not powered to detect statistical differences between thrombotic events, the overall low recurrence rate in morbidly obese patients is reassuring. Our study also suggests that there may be a decreased risk of major bleeding with apixaban, even in this population. A randomized controlled trial is needed to confirm these findings in a larger patient population. [Display omitted] DisclosuresKushnir:Janssen Pharmaceutical: Research Funding. Billett:Janssen Pharmaceutical: Research Funding.

Efficacy and safety of DOACs in patients with peripheral arterial disease: A systematic review and meta-analysis.

The efficacy and safety of direct oral anticoagulants (DOACs) in patients with peripheral arterial disease are not completely understood. Therefore, we conducted a meta-analysis to explore the effects of DOACs in this population. We systematically searched the PubMed, Cochrane Library, and Web of Science till April 2020 for relevant randomized controlled trials and observational studies, with no linguistic restrictions. The efficacy outcomes were cardiovascular death, stroke, myocardial infraction, major adverse cardiovascular events (MACE), acute limb ischemia, amputation, and target lesion revascularization. The safety outcome was major bleeding events. Random effects risk ratios with 95% confidence intervals were calculated. A total four randomized controlled trials were included in this meta-analysis. Among peripheral arterial disease patients, DOACs did not reduce the risk of cardiovascular death (RR = 1.02 95%CI 0.75-1.37, P = 0.92), stroke (RR = 0.73 95%CI 0.46-1.14, P = 0.16), myocardial infraction (RR = 0.85 95%CI 0.70-1.03, P = 0.10), MACE (RR = 0.73 95%CI 0.46-1.14, P = 0.16), or amputation (RR = 0.73 95%CI 0.46-1.14, P = 0.16) compared with control. However, DOACs were associated with reduction in acute limb ischemia (RR = 0.67 95%CI 0.55-0.80, P < 0.01) and target lesion revascularization (RR = 0.89 95%CI 0.81-0.99, P = 0.02) at the expense of major bleeding events (RR = 1.43 95%CI 1.16-1.77, P < 0.01) compared with control. Based on current evidence, no significant difference in cardiovascular death, stroke, myocardial infraction, MACE, and amputation was found when DOACs were compared to antiplatelet monotherapy. The benefits of preventing target lesion revascularization and acute limb ischemia were balanced by amplified risk of major bleeding. Larger randomized controlled trials are needed to figure out the uncertainty around efficacy and safety of medications for peripheral arterial disease.

Анализ клинической эффективности и безопасности прямых пероральных антикоагулянтов у пациентов с фибрилляцией предсердий в реальной клинической практике

Aim: to assess the efficacy and safety of direct oral anticoagulants (DOACs) in patients with atrial fibrillation (AFib) in real-world clinical practice. Patients and Methods: this non-interventional prospective study enrolled 356 patients aged 50-75 years with AFib and creatinine clearance ≥50 ml/min. All patients were divided into three age-matched groups based on DOACs prescribed. Group 1 patients (n=120) received rivaroxaban 20 mg daily. Group 2 patients (n=112) received dabigatran etexilate 150 mg twice daily. Group 3 patients (n=124) received apixaban 5 mg twice daily. The groups were comparable in comorbidities and the risks of thrombotic and hemorrhagic complications. Followup was 2 years after starting treatment. Thrombotic complications, massive bleedings, and death for any reason were considered end-points. Results: no significant differences in the rate of cardiogenic thrombotic complications between the groups were reported. In patients who received apixaban, fewer bleeding complications were diagnosed (insignificant differences). Conclusions: the efficacy and safety of DOACs in patients over 50 years are similar. KEYWORDS: atrial fibrillation, oral anticoagulants, thrombotic complications, infarction, stroke, bleedings. FOR CITATION: Khruslov M.V., Sorokina A.S., Sapel'nikova Yu.A., Vavilova T.V. Clinical efficacy and safety of direct oral anticoagulants in patients with atrial fibrillation in real-world clinical practice. Russian Medical Inquiry. 2021;5(4):196–199 (in Russ.). DOI: 10.32364/2587-6821-2021-5-4-196-199.

Intracranial hemorrhage with direct oral anticoagulants in patients with brain metastases.

Direct oral anticoagulants (DOACs) are increasingly prescribed in treatment of cancer-associated thrombosis, but limited data exist regarding safety of DOACs in patients with brain metastases. We aimed to determine the incidence of intracranial hemorrhage (ICH) in patients with brain metastases receiving DOACs or low-molecular-weight heparin (LMWH) for venous thromboembolism or atrial fibrillation. An international 2-center retrospective cohort study was designed. Follow-up started on the first day of concomitant anticoagulation and brain tumor diagnosis. At least 2 brain imaging studies were mandated. The primary outcome was the cumulative incidence of any spontaneous ICH at 12-month follow-up with death as a competing risk. Major ICH was defined as spontaneous, ≥10 mL in volume, symptomatic, or requiring surgical intervention. Imaging studies were centrally reviewed by a neuroradiologist blinded for anticoagulant type. PANWARDS (platelets, albumin, no congestive heart failure, warfarin, age, race, diastolic blood pressure, stroke) score for prediction of ICH was calculated. We included 96 patients with brain metastases (41 DOAC, 55 LMWH). The 12-month cumulative incidence of major ICH was 5.1% in DOAC-treated patients and 11.1% in those treated with LMWH (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.09-2.21). When anticoagulation was analyzed as a time-varying covariate, the risk of any ICH did not differ between DOAC- and LMWH-treated patients (HR, 0.98; 95% CI, 0.28-3.40). PANWARDS score was not associated with ICH risk. This international 2-center study suggests comparable safety of LMWH and DOACs in patients with brain metastases.

Efficacy and safety of direct oral anticoagulants for secondary prevention of cancer associated thrombosis: a meta-analysis of randomized controlled trials

Direct oral anticoagulants (DOACs) may be good alternatives to low molecular weight heparin (LMWH) or vitamin K antagonists (VKA) for treatment of cancer associated thrombosis (CAT). We conducted a meta-analysis of ten randomized clinical trials to evaluate the efficacy and safety of DOACs in patients with CAT. All had study populations composed in entirety or in part of patients with CAT. The primary outcome (efficacy) was recurrent VTE and the secondary outcomes (safety outcomes) included major bleeding, clinically relevant non-major bleeding (CRNMB), and all bleeding (major bleeding + CRNMB). Participants treated with DOACs had lower risk of recurrent VTE, overall (RR 0.63; 95% CI 0.51–0.79; p < 0.0001), compared to LMWH (RR 0.57; 95% CI 0.40–0.83; p = 0.003), but not compared to VKA (RR 0.69; 95% CI 0.44–1.06; p = 0.09). Compared to LMWH, DOACs showed no difference in major bleeding risk (RR 1.31; 95% CI 0.78–2.18; p = 0.31), though had higher risk of CRNMB (RR 1.60; 95% CI 1.13–2.26; p = 0.008) and all bleeding (RR 1.49; 95% CI 1.10–2.01; p = 0.010). These results indicate that DOACs are more effective than LMWH for prevention of recurrent VTE with CAT though carry an increased risk for non-major bleeding compared to standard of care, LMWH.

Direct Oral Anticoagulant for the Treatment of VTE in Cancer Patients: A Systematic Review and Meta-analysis.

Recent clinical guidelines suggest direct oral anticoagulants (DOACs) as treatment for cancer-associated thrombosis (CAT), but the strength of such recommendations was not clear. Newly released trials add uncertainties to the benefit and risk assessment between DOACs and conventional therapy (low-molecular-weight heparin [LMWH] or vitamin K antagonists [VKAs]). To evaluate the efficacy and safety of DOACs in patients with CAT, as compared with LMWH and VKAs. PubMed, EMBASE, Cochrane Library, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched. Randomized controlled trials (RCTs) that reported outcomes of DOACs for treating CAT were included. Relative risk (RR), risk difference, and 95% CIs were pooled using the Mantel-Haenszel method. A total of 8 RCTs were included. DOACs significantly reduced VTE recurrence (RR = 0.59; 95% CI = 0.48-0.73) compared with conventional therapy. Results were similar in the LMWH and VKA subgroups. DOACs had a higher, though nonsignificant, risk of major bleeding compared with LMWH (RR = 1.33; 95% CI = 0.94-1.89) but lower risk of major bleeding compared with VKAs (RR = 0.60; 95% CI = 0.39-0.93). Findings were consistent across patients with active cancer and history of cancer. DOACs have better efficacy to prevent recurrent VTE compared with conventional therapy. Regarding the safety profile, DOACs may carry higher risk of bleeding compared with LMWH but lower risk of bleeding compared with VKAs. Further studies are needed to inform the optimal anticoagulation approach for different types of cancers.

Registry of antithrombotic therapy in atrial fibrillation patients with bioprosthetic valves: A retrospective observational study

BackgroundThe incidence of cardiovascular diseases, including valvular heart disease and atrial fibrillation (AF), is rising as the elderly population increases. For patients with AF and bioprosthetic valves, current treatment guidelines for antithrombotic therapy vary by country, likely due to a lack of robust study data. MethodsWe conducted a multicenter, retrospective, observational analysis of 214 Japanese AF patients after bioprosthetic valve replacement in real-world clinical practice. The primary efficacy endpoint was the incidence of stroke/systemic embolism, and the primary safety endpoint was major bleeding. ResultsThe mean observation period was 46.0 months. Warfarin was administered to 176 patients (82.2%), direct oral anticoagulants (DOAC) to 16 patients (7.5%), and antiplatelet drugs to 13 patients (6.1%). The number of patients who were treated with DOAC was increasing in the later period of registration. Stroke/systemic embolism was observed in 14 patients [1.77 patients/100 person-years (PY)]. Major bleeding was observed in 22 patients (2.83/100 PY). ConclusionsIn a current real-world setting in Japan, warfarin was the most commonly used treatment in AF patients with bioprosthetic valves, but there was an increasing trend of DOAC-treated patients. Further investigations are needed to confirm the efficacy and safety of DOAC in patients with bioprosthetic valves.

Direct Oral Anticoagulants in Patients With Atrial Fibrillation and Liver Disease

BackgroundAdvanced liver disease is known to increase the risk for bleeding and affects the hepatic clearance and metabolism of drugs. Subjects with active liver disease were excluded from pivotal clinical trials of direct oral anticoagulants (DOACs), so the evidence regarding the efficacy and safety of DOACs in patients with liver disease is lacking. ObjectivesThe aim of this study was to compare DOACs with warfarin in patients with nonvalvular atrial fibrillation and liver disease. MethodsUsing the Korean National Health Insurance Service database, subjects with atrial fibrillation and active liver disease treated with oral anticoagulation were included (12,778 with warfarin and 24,575 with DOACs), and analyzed ischemic stroke, intracranial hemorrhage, gastrointestinal bleeding, major bleeding, all-cause death, and the composite outcome. Propensity score weighting was used to balance covariates between the 2 groups. ResultsDOACs were associated with lower risks for ischemic stroke (hazard ratio [HR]: 0.548; 95% confidence interval [CI]: 0.485 to 0.618), intracranial hemorrhage (HR: 0.479; 95% CI 0.394 to 0.581), gastrointestinal bleeding (HR: 0.819; 95% CI: 0.619 to 0.949), major bleeding (HR: 0.650; 95% CI: 0.575 to 0.736), all-cause death (HR: 0.698; 95% CI: 0.636 to 0.765), and the composite outcome (HR: 0.610; 95% CI: 0.567 to 0.656) than warfarin. Among the total study population, 13% of patients (n = 4,942) were identified as having significant active liver disease. A consistent benefit was observed in patients with significant active liver disease (HR for the composite outcome: 0.691; 95% CI: 0.577 to 0.827). ConclusionsIn this large Asian population with atrial fibrillation and liver disease, DOACs showed better effectiveness and safety than warfarin, which was consistent in those with significant active liver disease.

Direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer.

Direct oral anticoagulants for the treatment of venous thromboembolism in patients with cancer.

Abstract 17373: Prescription Patterns and Outcomes of Direct Oral Anticoagulants and Warfarin in Patients With Atrial Fibrillation a Real World Analysis

Introduction: Direct Oral Anticoagulants (DOACs) are used for stroke prevention in Atrial Fibrillation (AF). Hypothesis: We sought to evaluate differences in prescription patterns of DOACs and warfarin in new onset AF patients in relation to CHA2DS2Vasc score and compare outcomes of ischemic stroke, gastrointestinal (GI) bleed and intracranial hemorrhage (ICH) between DOACs and warfarin. Methods: All patients with a new diagnosis of AF from 2014 to 2017 were identified from the admission database at the University of Arkansas for Medical Sciences, AR, U.S.A. Trends in anticoagulant prescription were plotted in relation to CHA2DS2Vasc score. Baseline characteristics were compared using t-test and chi-square test as appropriate. Multivariate logistic regression was used to identify independent predictors of clinical outcomes of interest. Results: We examined a total of 2362 patients (1306 on warfarin and 1056 on DOACs). Prescription rates of warfarin increased with increasing CHA2DS2Vasc (Fig 1). Patients on warfarin had a higher prevalence of hypertension, diabetes, heart failure, renal failure and liver disease (Table 1a). On multivariate analysis, there was no difference in the incidence of ischemic stroke and GI bleeding between warfarin and DOACs (Table 1b). However, there was a trend towards lower incidence of ICH in DOAC group (p=0.06), despite wider usage in patients with higher CHA2DS2Vasc score. Conclusions: In a real-world setting, the use of DOACs was lower in patients with high CHA2DS2Vasc score compared with warfarin. Trend towards lower incidence of ICH was present in DOAC group. Further larger studies assessing safety of DOACs in patients with high CHA2DS2Vasc are needed.

Comparative effectiveness and safety of apixaban, dabigatran, and rivaroxaban in patients with non-valvular atrial fibrillation

BackgroundThe comparative effectiveness and safety of individual direct oral anticoagulants (DOACs) in clinical practice is largely unknown. The study objectives were to compare effectiveness and safety of DOACs in patients with non-valvular atrial fibrillation (NVAF). MethodsBased on nationwide registers we established a population-based historical cohort study of 12,638 new users of standard dose DOACs (apixaban 5 mg twice daily, dabigatran 150 mg twice daily and rivaroxaban 20 mg once daily) with NVAF in Denmark, July 2013 to March 2016. Patients were matched on propensity scores in a 1:1 ratio comparing apixaban vs. dabigatran (for a total of 6470 patients), apixaban vs. rivaroxaban (7352 patients), and rivaroxaban vs. dabigatran (5440 patients). Hazard ratios (HRs) for stroke or systemic embolism (effectiveness outcome) and major bleeding (safety outcome) were estimated. ResultsIn propensity-matched comparisons of the risk of stroke or systemic embolism, the HRs were 1.27 (95% confidence interval [CI], 0.82–1.96) for apixaban vs. dabigatran, 1.25 (95% CI, 0.87–1.79) for apixaban vs. rivaroxaban, and 1.17 (95% CI, 0.69–1.96) for rivaroxaban vs. dabigatran. For the risk of major bleeding, the HRs were 0.94 (95% CI, 0.62–1.41) for apixaban vs. dabigatran, 0.88 (95% CI, 0.64–1.22) for apixaban vs. rivaroxaban, and 1.35 (95% CI, 0.91–2.00) for rivaroxaban vs. dabigatran. ConclusionsAmong patients with NVAF in routine clinical practice, there were no statistically significant differences in risk of stroke or systemic embolism or major bleeding in propensity-matched comparisons between apixaban, dabigatran, and rivaroxaban used in standard doses. While analyses indicate that more than moderate differences can be excluded, smaller differences cannot be ruled out.

Acute haemorrhagic tamponade in cancer patients receiving direct oral anticoagulant: case series.

The use of direct oral anticoagulants (DOACs) is on the rise in the general population. However, data related to the safety of DOACs in patients with malignancy are limited. In this brief report, we present a series of three cases of haemorrhagic pericardial effusions and tamponade in patients receiving DOACs while undergoing cancer therapy. These three cases were all observed within a period of 6 weeks at a single institution and occurred shortly after the initiation of anticoagulation with one of the DOACs. Two of these patients had evidence of neoplastic pericardial process and were being treated with immunotherapy. The third patient was receiving targeted cancer therapy with a drug known to be associated with increased bleeding risks. Haemorrhagic pericarditis may represent a unique type of DOACs-related complications in subgroups of cancer patients with neoplastic pericardial disease and/or complex pharmacodynamics drug–drug interaction. The purpose of this report is to raise awareness of the lack of conclusive safety data of DOACs in certain cancer patients and to remind clinical providers of the National Comprehensive Cancer Network guidelines recommending against their use in patients with malignancy on the basis of limited safety data in patients undergoing cancer therapies.

SAFETY OF DIRECT ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: A TWO-YEAR COHORT STUDY

Real-life clinical application of anticoagulant drugs is currently one of the most promising trends in cardiology. With relation to initial prescription of anticoagulants, the updated 2016 guidelines on the management of patients with atrial fibrillation (AF) highlight direct oral anticoagulants (DOAC) rather than vitamin K antagonists, but, unfortunately, they are not clear about whether different DOAC have the same clinical effect of there is a significant difference. Material and methods . We conducted a comparative analysis of the safety of DOAC in patients with non-valvular AF and attempted to identify the potential predictors of hemorrhagic events in order to assess the predictive value of bleeding risk scores. For this purpose, we observed 117 patients with non-valvular AF who received DOAC to prevent TEC for 2 years (24 months). Results. Over the entire period of follow-up, no major bleeding or thromboembolic complications were recorded, supporting the good efficacy and safety profile of DOAC. We analysed the prognostic value of various scores and found that HAS-BLED had the highest predictive value in the group of patients treated with the direct thrombin inhibitor (dabigatran). Treatment with factor Xa inhibitors (rivaroxaban and apixaban) did not demonstrate a similar trend. Conclusion. Over the 2-year follow-up of 117 patients treated with DOAC, we were able to show that this group of drugs in patients with non-valvular AF is effective and safe given that adequate doses in accordance with the instructions are administered; this is true for both direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban and apixaban). HAS-BLED was prognostically more accurate when the direct thrombin inhibitor dabigatran was administered.