Acute upper gastrointestinal bleeding in patients on long-term oral anticoagulation therapy： Endoscopic findings, clinical management and outcome

AIM: Acute gastrointestinal bleeding is a severe complication in patients receiving long-term oral anticoagulant therapy. The purpose of this study was to describe the causes and clinical outcome of these patients. METHODS: From January 1999 to October 2003, 111 patients with acute upper gastrointestinal bleeding (AUGIB) were hospitalized while on oral anticoagulants. The causes and clinical outcome of these patients were compared with those of 604 patients hospitalized during 2000-2001 with AUGIB who were not taking warfarin. RESULTS: The most common cause of bleeding was peptic ulcer in 51 patients (45%) receiving anticoagulants compared to 359/604 (59.4%) patients not receiving warfarin (P<0.05). No identifiable source of bleeding could be found in 33 patients (29.7%) compared to 31/604 (5.1%) patients not receiving anticoagulants (P=0.0001). The majority of patients with concurrent use of non-steroidal anti-inflammatory drugs (NSAIDs) (26/35, 74.3%) had a peptic ulcer as a cause of bleeding while 32/76 (40.8%) patients not taking a great dose of NSAIDs had a negative upper and lower gastrointestinal endoscopy. Endoscopic hemostasis was applied and no complication was reported. Six patients (5.4%) were operated due to continuing or recurrent hemorrhage, compared to 23/604 (3.8%) patients not receiving anticoagulants. Four patients died, the overall mortality was 3.6% in patients with AUGIB due to anticoagulants, which was not different from that in patients not receiving anticoagulant therapy. CONCLUSION: Patients with AUGIB while on long-term anticoagulant therapy had a clinical outcome, which is not different from that of patients not taking anticoagulants. Early endoscopy is important for the management of these patients and endoscopic hemostasis can be safely applied.     

Effect of direct-acting oral anticoagulants (DOACs) on bleeding and blood product usage in cardiac surgery compared to warfarin and controls

In this retrospective, single-centre, observational study, we assessed (i) use of anticoagulant and antiplatelet (AP) therapy, (ii) the duration of direct-acting oral anticoagulant (DOAC) discontinuation, (iii) renal function and (iv) PT and APTT as predictors of bleeding and blood product usage; in adults (>18 years) undergoing major cardiac surgery from 01.01.2015 to 31.12.2018. Comparisons were made between each treatment group (warfarin, DOAC and DOAC + AP) and untreated controls, and between warfarin and DOAC. A total of 2928 patients were included for analysis. Median (range) of DOAC discontinuation prior to surgery was five days (1–22) for DOAC and five days (2–7) for DOAC + AP. There were no differences in bleeding between anticoagulant groups versus control, or DOAC versus warfarin. There were no differences in blood product use between DOAC and warfarin patients. The duration of DOAC discontinuation but not the creatinine clearance influenced bleeding and blood products use. Thrombosis occurred in 0·7% and 3·1% in controls and patients on warfarin respectively (P = 0·099) with none among patients on DOAC or DOAC + AP. The PT/APTT had no predictive value. Median five-day discontinuation of DOAC +/− AP irrespective of renal function prevents an increase in bleeding compared to patients on warfarin or controls with no increase in thrombosis.     

Direct oral anticoagulants for atrial fibrillation in patients with congenital factor VII deficiency

The management of anticoagulant therapy (OAT) in patients with factor VII (FVII) deficiency is a very challenging clinical issue, as warfarin further reduces FVII levels, thus potentially increasing bleeding risk. On the other hand, the International Normalized Ratio test is misleading in such patients, as they do not reflect the actual level of global inhibition of the coagulation system. We report here three cases of patients with a moderate FVII deficiency and receiving direct oral anticoagulants (DOAC) for prevention of cardioembolism in atrial fibrillation. Of note, two of them experienced a treatment failure while on warfarin, while DOAC treatment was not associated with thrombotic or hemorrhagic adverse events. DOAC are very attractive for the management of OAT in FVII deficient patients, because they do not require monitoring by tests affected by the inherited defect, and their mechanism of action is FVII‐independent.     

Severity of Gastrointestinal Bleeding in Patients Treated with Direct-Acting Oral Anticoagulants

Background

Direct-acting oral anticoagulants (DOACs), which have gained approval for stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism, have become increasingly preferred over warfarin given their predictable pharmacodynamics, lack of required monitoring, and superior outcomes. Direct-acting oral anticoagulants have been shown to be associated with an increased frequency of gastrointestinal bleeding compared with warfarin, but the severity and characteristics of gastrointestinal bleeding in these patients is poorly understood.

Heparin bridge therapy and post-polypectomy bleeding

AIM To identify risk factors for post-polypectomy bleeding(PPB), focusing on antithrombotic agents. METHODS This was a case-control study based on medical records at a single center. PPB was defined as bleeding that occurred 6 h to 10 d after colonoscopic polypectomy and required endoscopic hemostasis. As risk factors for PPB, patient-related factors including anticoagulants, antiplatelets and heparin bridge therapy as well as polyp- and procedure-related factors were evaluated. All colonoscopic hot polypectomies, endoscopic mucosal resections and endoscopic submucosal dissections performed between January 2011 and December 2014 were reviewed. RESULTS PPB occurred in 29(3.7%) of 788 polypectomies performed during the study period. Antiplatelet or anticoagulant agents were prescribed for 210(26.6%)patients and were ceased before polypectomy except for aspirin and cilostazol in 19 cases. Bridging therapy using intravenous unfractionated heparin was adopted for 73 patients. The univariate analysis revealed that anticoagulants, heparin bridge, and anticoagulants plus heparin bridge were significantly associated with PPB(P 0.0001) whereas antiplatelets and antiplatelets plus heparin were not. None of the other factors including age, gender, location, size, shape, number of resected polyps, prophylactic clipping and resection method were correlated with PPB. The multivariate analysis demonstrated that anticoagulants and anticoagulants plus heparin bridge therapy were significant risk factors for PPB(P 0.0001). Of the 29 PPB cases, 4 required transfusions and none required surgery. A thromboembolic event occurred in a patient who took anticoagulant. CONCLUSION Patients taking anticoagulants have an increased risk of PPB, even if the anticoagulants are interrupted before polypectomy. Heparin-bridge therapy might be responsible for the increased PPB in patients taking anticoagulants.     

Assessment of delayed bleeding after endoscopic submucosal dissection of early-stage gastrointestinal tumors in patients receiving direct oral anticoagulants

Delayed bleeding is a major and serious adverse event of endoscopic submucosal dissection(ESD) for early-stage gastrointestinal tumors. The rate of post-ESD bleeding for gastric cancer is higher(around 5%-8%) than that for esophagus,duodenum and colon cancer(around 2%-4%). Although investigations into the risk factors for post-ESD bleeding have identified several procedure-,lesion-,physician-and patient-related factors,use of antithrombotic drugs,especially anticoagulants [direct oral anticoagul...     

Renal function in atrial fibrillation patients switched from warfarin to a direct oral anticoagulant

All available direct oral anticoagulants (DOACs) are at least partially eliminated by the kidneys. These agents are increasingly being used as alternatives to warfarin for stroke prevention in patients with atrial fibrillation. The aim of this study was to identify changes in renal function and associated DOAC dosing implications in a multicenter cohort of atrial fibrillation patients switched from warfarin to DOAC treatment. We included all patients in the Michigan Anticoagulation Quality Improvement Initiative cohort who switched from warfarin to a DOAC with atrial fibrillation as their anticoagulant indication between 2009 and 2014, and who had at least two creatinine values. Compliance with FDA-recommended dosing based on renal function was assessed. Of the 189 patients switched from warfarin to a DOAC, 34 (18.0 %) had a baseline creatinine clearance <50 mL/min and 23 (12.2 %) experienced important fluctuations in renal function. Of these 23 patients, 6 (26.1 %) should have impacted the DOAC dosing, but only 1 patient actually received an appropriate dose adjustment. Additionally, 15 (7.9 %) of patients on DOACs had a dose change performed, but only one patient demonstrated a change in renal function to justify the dose adjustment. Most atrial fibrillation patients who switched from warfarin to a DOAC had stable renal function. However, the majority of patients who had a change in renal function did not receive the indicated dose change. As the use of DOACs expands, monitoring of renal function and appropriate dose adjustments are critical.     

Anticoagulation prescribing patterns in patients with cancer

Cancer is a known hypercoagulable state that leads to an increased risk of venous thromboembolism (VTE). Low molecular weight heparin remains the preferred anticoagulant for VTE in patients with cancer over vitamin K antagonist. However, the preferred anticoagulant in prevention of stroke and systemic embolism in atrial fibrillation (AF) in patients with cancer has yet to be determined. The direct oral anticoagulants (DOACs) are increasingly being utilized; however their role in cancer has only recently been investigated. The objective of this retrospective cohort was to describe real-world anticoagulation prescribing patterns in cancer patients at a large academic medical center between January 1, 2013 and October 31, 2016. We sought to assess the safety, tolerability, and efficacy of DOACs in patients with cancer for either VTE and/or AF. Patient demographic, clinical characteristics, as well as bleeding and thrombotic events were collected. There were 214 patients in our analysis, of which 71 patients (33%) received a DOAC [apixaban (n?=?22), dabigatran (n?=?17), and rivaroxaban (n?=?32)]. There were fewer bleeding events and/or discontinuations in the DOAC group compared to enoxaparin (13 vs. 27, p?=?0.022). There was no difference in major or minor bleeds or thromboembolic events in comparing DOAC to enoxaparin or DOAC to warfarin. This was a retrospective, single-institution study assessing the safety and efficacy of DOACs compared to warfarin or enoxaparin in patients with cancer. DOACs may represent an alternative to warfarin or enoxaparin in patients with cancer for VTE and/or stroke reduction in AF.     

Effectiveness and safety of oral anticoagulants in patients with sickle cell disease and venous thromboembolism: a retrospective cohort study

Patients with sickle cell disease (SCD) experience initial and recurrent venous thromboembolism (VTE) more commonly and at a younger age than the general population, and it confers a higher mortality for patients with SCD. However, limited evidence is available to guide anticoagulant use for VTE treatment in this population. The primary objective of this study is to characterize the effectiveness and safety of direct oral anticoagulants (DOAC) and warfarin for VTE treatment among patients with SCD. This single-center retrospective study includes adult patients with SCD who were diagnosed with VTE. Data was obtained from review of electronic health records for the 6 months after VTE diagnosis. Among the 22 patients treated initially with a DOAC, 6 (27%) developed recurrent VTE, none experienced major bleeding, and 3 (14%) experienced clinically relevant non-major bleeding (CRNMB). Similarly, of 15 patients initially treated with warfarin, 3 (20%) developed a recurrent VTE, 1 (7%) experienced major bleeding, and 2 (13%) experienced CRNMB. Twelve patients received more than one oral anticoagulant during the study period, most commonly due to a recurrent VTE, concern for non-adherence, or subtherapeutic INR. Overall, the incidence of VTE recurrence and bleeding events were similar between groups, but occurred at a higher rate than those found in major clinical trials of anticoagulant agents. Prescribers should continue to individualize therapeutic decision-making regarding oral anticoagulant therapy for VTE treatment for individuals with SCD based on patient-specific factors and anticipated ability to adhere to the drug regimen or required monitoring.     

The Introduction of Direct Oral Anticoagulants Has Not Resolved Treatment Gaps for Frail Patients With Nonvalvular Atrial Fibrillation

BackgroundThe extent to which the introduction of direct oral anticoagulants (DOACs) influenced treatment patterns in frail and nonfrail patients with nonvalvular atrial fibrillation (NVAF) is unclear.MethodsThis was a retrospective cohort study of all Albertans 20 years or older who were discharged from an emergency department or hospital with a new diagnosis of NVAF between April 1, 2009, and March 31, 2019. The Hospital Frailty Risk Score was used to define frailty and the CHA₂DS₂-VASc and CHADS-65 scores were used to identify if anticoagulation was indicated.ResultsAmong 75,796 patients (median age, 75 years; 45% female) with a new diagnosis of NVAF, 17,143 (22.6%) were frail. Although guideline criteria for anticoagulation were more commonly met by frail patients than nonfrail patients (92.1% vs 74.2%, for CHA₂DS₂-VASc, and 96.8% vs 85.8% for CHADS-65; both P < 0.0001), frail patients were less likely to receive any anticoagulant, even after those with contraindications to anticoagulation were excluded (adjusted odds ratio, 0.61; 95% confidence interval, 0.58-0.64). After DOACs became available, anticoagulant prescribing for patients with guideline indications increased more in nonfrail patients (from 42.4% to 68.2%) than in frail patients (from 29.0% to 52.2%) and frail patients were less likely to receive a DOAC than warfarin (adjusted odds ratio, 0.66; 95% confidence interval, 0.54-0.81).ConclusionsAlthough they stand to potentially derive greater benefits from anticoagulation, frail patients were less likely to receive an anticoagulant and, if anticoagulated, they were more likely to receive warfarin than a DOAC. The introduction of DOACs has increased anticoagulation rates but not resolved treatment gaps for frail patients with NVAF.     

Initiation of direct oral anticoagulants versus warfarin for venous thromboembolism: impact on time to hospital discharge

The objective of this project was to compare the time from initiation of oral anticoagulation to hospital discharge between warfarin and direct oral anticoagulants (DOACs) for the treatment of acute venous thromboembolism (VTE). This retrospective observational study was done at a single VA medical center. A total of 107 patients were included, with 42 patients (39%) in the DOAC group, which included rivaroxaban, dabigatran, and apixaban, and 65 patients (61%) in the warfarin group. Variables collected through chart review included comorbid conditions, time from initiation of oral anticoagulation to discharge, emergency department (ED) visits and readmission within 30 or 90 days, and bleeding events. The DOAC group had a shorter time to discharge compared to the warfarin group (28 vs. 114 h, p?<?0.001). There were similar 30 and 90-day hospital readmission rates and/or ED visits for DOACs (23.8 and 33.3%) compared to warfarin (18.5 and 30.8%), including those related to bleeding of any severity (11.9% for DOACs vs. 9.2% for warfarin; p?=?0.75). There was one major bleeding event in the DOAC group and two in the warfarin group. The use of DOACs for the treatment of acute VTE in hospitalized patients was associated with shorter time to hospital discharge when compared to warfarin.     

Safety and effectiveness of direct oral anticoagulants following ultrasound-assisted catheter directed thrombolysis for venous thromboembolism

Ultrasound-assisted catheter-directed thrombolysis (USAT) is a novel approach for the treatment of venous thromboembolism (VTE) that is thought to be associated with a decreased risk of bleeding. Direct oral anticoagulants (DOACs) are approved for the treatment of VTE but have not been studied in a post-fibrinolysis setting. The intention of this retrospective observational study was to determine the safety and effectiveness of DOACs compared to the vitamin-K-antagonist (VKA) warfarin following USAT in patients with documented VTE. Included patients were aged 18 years or older who had documented VTE and received oral anticoagulation with either a DOAC or VKA following USAT. The primary outcome of this study was to compare the 90-day composite incidence of major and minor bleeding and recurrent VTE between patients receiving DOACs after USAT to those receiving VKA after USAT. Similar rates of bleeding and recurrent VTE were observed (4/42; 9.5% in the DOAC group versus 2/34; 5.9% in the VKA group). The use of DOAC therapy post-USAT for VTE was not associated with higher rates of 90-day major or minor bleeding or 90-day recurrent VTE.     

The efficacy and safety of direct oral anticoagulants in patients with chronic renal insufficiency: A review of the literature

Direct oral anticoagulants (DOACs) have been shown to be superior to vitamin K antagonists (VKAs) in regards to safety and efficacy in numerous clinical trials and are now the preferred oral anticoagulant by multiple professional societies. However, patients with significant levels of organ dysfunction were excluded from all major clinical trials, leaving the clinical benefit in these subsets uncertain. Patients with chronic kidney disease (CKD) specifically often require anticoagulation for acute or long‐term indications such as venous thromboembolism, atrial fibrillation, or mechanical heart valves. The efficacy and safety of anticoagulation in patients with renal failure is less certain, however, particularly with DOACs which have altered pharmacokinetics in patients with renal failure and limited observational data on their use in this population. In this review, we compile the most up to date data on the DOAC use in patients with CKD. DOAC use in patients with ESRD and advanced CKD is increasing despite the presence of a clear benefit, and with the potential for increased risk of bleeding compared to warfarin. Apixaban has the greatest amount of outcomes research supporting its use over warfarin in this patient population; however, further research on DOAC safety and efficacy in those with advanced CKD is still needed.     

National Trends in Ambulatory Oral Anticoagulant Use

Background

Four direct oral anticoagulants (DOACs) have been brought to market for the treatment of nonvalvular atrial fibrillation and venous thromboembolism. Many forces, including numerous positive trial results, emerging safety concerns, marketing, and promotion, may shape DOAC adoption by providers. However, relatively little is known regarding their ambulatory utilization compared with warfarin, as well as the degree to which they have decreased under-treatment of atrial fibrillation.

Methods

We used the IMS Health National Disease and Therapeutic Index, a nationally representative audit of outpatient office visits, to estimate the use of warfarin and DOACs between 2009 and 2014.

Results

Overall, visits with anticoagulation use increased from 2.05 (95% confidence interval [CI], 1.82-2.27) to 2.83 (95% CI, 2.49-3.17) million (M) quarterly visits (P < .001). Of these, DOAC use has grown to 4.21M (95% CI, 3.63M-4.79M; 38.2% of total) treatment visits in 2014 since their introduction in 2010. Use of all oral anticoagulants in treatment visits for atrial fibrillation has increased from 0.88M (95% CI, 0.74M-1.02M) to 1.72M (95% CI, 1.47M-1.97M; P < .001), with similar DOAC and warfarin use in 2014. Atrial fibrillation visits with anticoagulant use increased from 51.9% (95% CI, 50.4%-53.8%) to 66.9% (95% CI, 65.0%-69.3%) between 2009 and 2014 (P < .001). In 2014, rivaroxaban was the most commonly prescribed DOAC for atrial fibrillation (47.9% of office visits), followed by apixaban (26.5%) and dabigatran (25.5%).

Conclusions

Direct oral anticoagulants have been adopted rapidly, matching the use of warfarin, and are associated with increased use of oral anticoagulation for patients with atrial fibrillation.     

Relationship between the nutritional status and safety and efficacy outcomes in atrial fibrillation patients aged 80 years and over receiving oral anticoagulants

BackgroundMalnutrition has been reported to be associated with worse clinical outcomes in various cardiovascular diseases. We aimed to investigate the clinical significance of the nutritional status in atrial fibrillation (AF) patients aged 80 years and over receiving oral anticoagulants (OACs), focusing on the difference between direct OACs (DOACs) and warfarin treatment.MethodsThis was a retrospective and observational study. We enrolled 332 consecutive AF patients aged 80 years and over who were treated with OACs: DOACs (n = 256) and warfarin (n = 76). A controlling nutritional status (CONUT) score was used to evaluate the nutritional status. The enrolled patients were divided into two groups based on the CONUT score: CONUT score <5 (n = 239) and CONUT score ≥5 (n = 93) groups. We investigated the relationship between the nutritional status and clinical outcomes.ResultsThe CONUT score ≥5 group had significantly higher incidence of major bleeding (MB) compared to the CONUT score <5 group (4.6/100 person-years vs. 0.7/100 person-years, p < 0.01). On Cox hazard analysis, CONUT score ≥5 group was significantly associated with increased MB compared with the CONUT score <5 group (hazard ratio: 5.80, 95% confidence interval: 1.44–23.33, p = 0.013). In the DOAC group, the incidence of MB did not differ between the CONUT score ≥5 and CONUT score <5 groups (p = 0.54). In the warfarin group, MB occurred more frequently in the CONUT score ≥5 group than CONUT score <5 group (p < 0.01). There was no significant difference in the incidence of thromboembolic events between the CONUT score ≥5 and CONUT score <5 groups in both the DOAC and warfarin groups.ConclusionsThe prognostic values of the nutritional status based on the CONUT score for MB differed between AF patients aged 80 years and over receiving DOACs and those receiving warfarin. It may be favorable to use DOACs to avoid bleeding events in those with malnutrition.     

Hospital length of stay in patients initiated on direct oral anticoagulants versus warfarin for venous thromboembolism: a real-world single-center study

This study was conducted to describe the real-world hospital length of stay in patients treated with all of the U.S. Food and Drug Administration approved direct oral anticoagulants (DOACs) versus warfarin for new-onset venous thromboembolism (VTE) at a large, tertiary, academic medical center. A retrospective cohort analysis of all adult patients diagnosed with acute onset VTE was conducted. Of the 441 patients included, 261 (57%) patients received DOACs versus 180 (41%) patients received warfarin. In the DOAC group, a total of 92 (35%) patients received rivaroxaban, followed by 83 (32%) patients received apixaban, 50 (19%) patients received dabigatran, and 36 (14%) patients received edoxaban. Patients initiated on DOACs had a statistically significant shorter hospital length of stay compared to patients initiated on warfarin (median 3 days, [IQR 0–5] vs. 8 days [IQR 5–11], P?<?0.05). Despite the shorter hospital length of stay in patients receiving DOACs, the overall reported differences between the DOACs group and the warfarin group in terms of recurrent VTE, major bleeding, intracranial bleeding, and gastrointestinal bleeding at 3 and 6 months were deemed to be statistically insignificant.     

Antiplatelet and anticoagulant therapy in patients with giant cell arteritis

OBJECTIVE: Vision loss and cerebrovascular accidents often complicate giant cell arteritis (GCA). Antiplatelet and anticoagulant therapy reduce the risk of stroke in other populations. We sought to determine whether antiplatelet or anticoagulant therapy reduces ischemic complications in patients with GCA. METHODS: A retrospective chart review for patients with GCA was conducted. Included patients fulfilled modified 1990 American College of Rheumatology criteria for GCA. Collected information included demographic data, dates of antiplatelet or anticoagulant use, vision loss or stroke, and presence of bleeding complications and cerebrovascular risk factors. RESULTS: A total of 143 patients were included with a mean followup period of 4 years. The cohort included 109 women (76%) and 34 men (24%) with a mean age of 71.8 years. A total of 104 patients (73%) had a biopsy-proven diagnosis. Eighty-six patients (60.1%) had received long-term antiplatelet or anticoagulant therapy, including 18 (12.6%) who did not start therapy until after an ischemic event had occurred. Antiplatelet agents or anticoagulants were not used in 57 patients (39.9%). Overall, 11 of 68 patients (16.2%) had an ischemic event while receiving antiplatelet or anticoagulant therapy, compared with 36 of 75 patients (48.0%) not receiving such therapy (P < 0.0005). Univariate analysis failed to show a statistical difference between groups in regard to cerebrovascular risk factors, age, sex, or biopsy-proven diagnosis. Bleeding complications occurred in 2 patients receiving aspirin, 1 patient receiving warfarin, and 5 patients who did not receive anticoagulant or antiplatelet therapy. CONCLUSION: Antiplatelet or anticoagulant therapy may reduce the risk of ischemic events in patients with GCA. An increased risk of bleeding complications was not observed.     

Outcomes of Direct Oral Anticoagulants in Patients With Mitral Stenosis

Background

Patients with mitral stenosis and atrial fibrillation (AF) require anticoagulation for stroke prevention. Thus far, all studies on direct oral anticoagulants (DOACs) have excluded patients with moderate to severe mitral stenosis.

Adverse events in patients taking apixaban or rivaroxaban who have undergone bariatric surgery: a retrospective case series

Journal of Thrombosis and Thrombolysis - Clinical trials comparing direct oral anticoagulants (DOAC) to warfarin excluded patients with a history of bariatric surgery. The anatomic changes from...