Evaluation of the Effectiveness and Safety of Direct Oral Anticoagulants in Elderly Patients With Nonvalvular Atrial Fibrillation Who Are Not Candidates for Warfarin in Real-World Setting.

ABSTRACT: Limited literature has established the role of direct oral anticoagulants (DOAC) for elderly patients with nonvalvular atrial fibrillation who are unsuited for warfarin. Therefore, the objectives of this study were to assess the effectiveness and safety of DOAC use in this vulnerable patient population. This was a retrospective propensity score matching cohort study. Among all patients aged 75+ years who were not candidates for warfarin, we matched those who initiated DOAC between September 2017 and September 2018 with those who did not receive DOAC or warfarin in a 1:1 ratio. Effectiveness outcome was a composite measure of stroke, transient ischemic attack, and pulmonary embolism. Safety outcome was a composite measure of non-trauma-related intracranial hemorrhage and gastrointestinal bleed. Unless patients died or lost membership, follow-up period for the effectiveness outcome was until the end of 2019, whereas the safety outcome was for a period up to 1 year. Conditional logistic regression was used to analyze both outcomes. We identified 7818 patients who met the inclusion criteria and started DOAC, which matched to 7818 patients who did not receive anticoagulants. The mean age was 82.3 ± 5.1 years, and 51.5% male. The DOAC group had a lower hazard ratio of 0.37 (confidence interval, 0.24-0.57; P < 0.01) for composite effectiveness outcomes, whereas no difference in the composite safety outcome (hazard ratio, 0.91; confidence interval, 0.65-1.25; P = 0.55) when compared with matched control. In conclusion, DOAC was found to be effective in preventing thromboembolic events in patients aged 75+ years with nonvalvular atrial fibrillation who were not eligible for warfarin.

Coagulation disorders in Duchenne muscular dystrophy? Results of a registry-based online survey.

Different complications of hemostasis have been reported in patients with Duchenne Muscular Dystrophy (DMD). These comprise an increased rate of bleeding-symptoms during scoliosis surgery but also thromboembolic complications such as pulmonary embolism, cerebral infarction, deep vein thrombosis or cardiac thrombus. For this cross-sectional study, personalized online survey-links were forwarded to 682 registered patients with a genetically confirmed diagnosis of DMD via the German-Austrian DMD patient registry (www.dmd-register.de). The questionnaire enquired data regarding the degree of mobility, disposition to hematoma, epistaxis and gum bleeding, occurrence of peri- and postsurgical hemorrhage, stroke, deep vein thrombosis, and cardiac thromboembolism. Further data on regular medication and age were recorded. Three-hundred-fifty-one DMD-patients completed the questionnaire (response rate of 51.5%). Of those, 164 (46.7%) were ambulatory and 187 (53.3%) were non-ambulatory. Age distribution was homogeneous. Two participants had a history of thromboembolic events (0.6%). Correlations analysis revealed no coherence with the degree of mobility, age or regular medication. A bleeding tendency was reported by 76 participants (21.7%). No significant correlations with age or degree of mobility were found. We found no association with underlying genetic variants. Results of this patient registry-based survey do not indicate a distinct DMD-specific risk for thromboembolic events that exceeds the risk by typical comorbidities of chronic immobility and cardiac insufficiency in advanced stages of the disease. The results of this survey suggest a mild bleeding tendency in this DMD cohort, whereas a selection bias cannot be excluded.

The atrial FibriLlatiOn real World management registry in the Middle East and Africa: design and rationale.

BACKGROUND: Atrial fibrillation is the most common cardiac arrhythmia, affecting 33.5 million patients globally. It is associated with increased morbidity, leading to significant clinical and economic burden. There exist only limited data in the Middle Eastern region from the existing registries. The goal of the FLOW-AF (atrial FibriLlatiOn real World management registry in the Middle East and Africa) registry is to evaluate the characteristics, treatment patterns, and clinical and economic outcomes associated with anticoagulation among patients newly diagnosed with nonvalvular atrial fibrillation in Egypt, Lebanon, the Kingdom of Saudi Arabia, and the United Arab Emirates. METHODS: This study will be a multicountry, multicenter, prospective observational registry aiming to enroll 1446 newly diagnosed nonvalvular atrial fibrillation patients at more than 20 sites across the four countries. During the recruitment period, patients will be included if they were newly diagnosed with nonvalvular atrial fibrillation and had initiated treatment for the prevention of stroke/systemic embolism. Patient data will be assessed prospectively at 6 and 12 months from their enrollment date. Demographics, clinical characteristics, antithrombotic treatments received, clinical outcomes, adverse events, healthcare resource utilization, and direct costs associated with management of nonvalvular atrial fibrillation will be collected and analyzed overall, by country, and by groups created based on treatment, demographics, and clinical characteristics, medical history and risk factors. CONCLUSION: The FLOW-AF registry will provide information on the uptake of oral anticoagulants, treatment patterns, clinical outcomes, and healthcare utilization and costs among newly diagnosed nonvalvular atrial fibrillation patients in the Middle Eastern region.

Characteristics and outcomes in patients with atrial fibrillation receiving direct oral anticoagulants in off-label doses.

BACKGROUND: We evaluated adherence to dosing criteria for patients with atrial fibrillation (AF) taking dabigatran or rivaroxaban and the impact of off-label dosing on thromboembolic and bleeding risk. METHODS: We used data for a retrospective cohort from a large U.S. health plan for Medicare beneficiaries age > =65 years with AF who initiated dabigatran or rivaroxaban during 2010-2016. Stroke and major bleeding were quantified in patients who were eligible for low dose but received standard dose, and in patients who were eligible for standard dose but received low dose. RESULTS: We identified 8035 and 19,712 patients who initiated dabigatran or rivaroxaban, respectively. Overall, 1401 (17.4%) and 7820 (39.7%) patients who received dabigatran and rivaroxaban met criteria for low dose, respectively. Of those, 959 (68.5%) and 3904 (49.9%) received standard dose. In contrast, 1013 (15.3%) and 2551 (21.5%) of patients eligible for standard dose dabigatran and rivaroxaban received low dose. Mean follow-up for patients eligible for low and standard dose dabigatran and rivaroxaban were 13.9, 15.1, 10.1, and 12.3 months, respectively. In unadjusted analyses, patients eligible for low or standard dose dabigatran and rivaroxaban but receiving off-label dose, had no differences in the rates of ischemic stroke. Among patients who met criteria for standard dose direct oral anticoagulants (DOAC), use of low dose was associated with significantly higher risk of any major bleeding (Dabigatran: HR = 1.44; 95% CI 1.14-1.8, P = 0.002, Rivaroxaban HR 1.34, 95% CI 1.11-1.6, P = 0.002) and gastrointestinal bleeding (Dabigatran: HR = 1.48; 95% CI 1.08-2, P = 0.016). In patients who met criteria for low dose DOACs, there was lower risk of major bleeding (Dabigatran: HR = 0.59; 95% CI 0.43-0.8, P < 0.001), gastrointestinal (Rivaroxaban: HR 0.79; 95% CI 0.64-0.98, P = 0.03) and intracranial bleeding (Dabigatran: HR = 0.33; 95% CI 0.12-0.9, P = 0.001) with standard dosing. After propensity matching, use of off-label doses was not associated with stroke, major, gastrointestinal or intracranial bleeding for either dabigatran or rivaroxaban. CONCLUSIONS: While a significant number of patients receive higher or lower dose of dabigatran and rivaroxaban than recommended, we found no evidence of significant impact on thromboembolic or hemorrhagic outcomes.

Adherence to oral anticoagulant treatment and risk factor assessment six months after DC-conversion of atrial fibrillation.

Objective. We wanted to study the adherence of oral anticoagulant treatment in patients 6 months after elective DC-cardioversion and to observe possible increases in CHA2DS2-VASc scores and new adverse outcomes. Design. Consecutive patients admitted for elective DC-cardioversion at Haukeland University Hospital during the period from June 2017 to April 2018 were screened. Only patients who had a DC-cardioversion performed were included. Baseline information was collected from hospital records and follow up information was gathered through a structured phone interview and the prescription database. Results. Of the 125 patients screened, 38 were excluded as DC-cardioversion was not performed. The included patients were contacted 6 months later, out of whom 77 (84%) responded. Three patients had discontinued oral anticoagulation therapy, but only one patient had done so in violation of Guidelines. Two patients had continued oral anticoagulant treatment despite lack of indication. Of the responding patients 89% were compliant, estimated by a Proportion of Days Covered > 80%. Three patients experienced a thromboembolic event, despite being on anticoagulation. The mean CHA2DS2-VASc score increased from 3.0 ± 1.4 to 3.3 ± 1.5, (p < .001). Less than half maintained sinus rhythm, the remaining had either atrial fibrillation (n = 30, 40%) or were unsure of their current rhythm (n = 9, 12%). A third received new cardiac interventions during follow up. Conclusion. We found an excellent adherence to Guidelines recommended therapy amongst our patients. CHA2DS2-VASc scores increased significantly during the 6-month observation period. From this we conclude there is a need for structured follow up to assess new risk factors.

Pediatric Noncerebral Thromboembolism: Etiological Assessment and Outcome.

OBJECTIVE: To report clinical presentation and etiologic investigation findings during pediatric noncerebral thromboembolism. METHODS: Retrospective study of cases of vascular non cerebral thromboses admitted in Medicine infantile A Department of the Children's Hospital of Tunis over 08 years. RESULTS: We confirmed 14 cases of non cerebral vascular thromboses. So that these accidents constitute 0,26 ‰ of the overall etiologies of hospitalizations in the Department. The mean age of our patients was 56±41 months [25 days-12 1/2 years]. The sex ratio was 1.8. The vascular incident was venous in 2/3 of cases. The clinical presentation was mainly painful swelling in four cases, abrupt dyspnea and hematemesis in three cases each and the incident was locally asymptomatic in four cases. Thromboses locations included deep vein thrombosis of limbs (n=6), vena cava thrombosis (n=1), portal thrombosis (n=4) and pulmonary embolism (n=3). The promoting factors identified were: tumors in seven cases, thrombophilias and catheterization in four cases each, trauma, surgery and Behçet disease in one case each. Eleven patients received anticoagulant treatment including unfractioned heparin in three cases and low molecular weight heparin in the other cases. No one died while four patients developed sequelae. CONCLUSION: Vascular thromboses are rare in children. They are mostly venous and diagnosed in ill children especially those having central venous catheters. Outcome of pediatric thromboembolism depends on efficient anticoagulation therapy which is well tolerated by children.

Arterial thromboembolic events preceding the diagnosis of cancer in older persons.

Cancer patients face an increased risk of arterial thromboembolism; however, it is uncertain when this excess risk begins. This study evaluated the risk of arterial thromboembolism before cancer diagnosis. Using the population-based Surveillance Epidemiology and End Results-Medicare linked dataset, we identified 374 331 patients ≥67 years of age with a new primary diagnosis of breast, lung, prostate, colorectal, bladder, uterine, pancreatic, gastric cancer, or non-Hodgkin lymphoma from 2005 through 2013. Cancer patients were individually matched by demographics and comorbidities to Medicare beneficiaries without cancer, who served as controls. Validated diagnosis codes were used to identify arterial thromboembolic events, defined as a composite of myocardial infarction or ischemic stroke. The Mantel-Haenszel estimator was used to compare risks of arterial thromboembolic events between cancer and noncancer groups during 30-day periods in the 360 days before date of cancer diagnosis. From 360 to 151 days before cancer diagnosis, the 30-day interval risks of arterial thromboembolic events were similar between cancer patients and matched controls. From 150 to 1 day before cancer diagnosis, the interval 30-day risks of arterial thromboembolic events were higher in cancer patients vs matched controls, progressively increasing as the cancer diagnosis date approached and peaking during the 30 days immediately before cancer diagnosis, when 2313 (0.62%) cancer patients were diagnosed with an arterial thromboembolic event vs 413 (0.11%) controls (odds ratio, 5.63; 95% confidence interval, 5.07-6.25). In conclusion, the risk of arterial thromboembolic events begins to increase 150 days before the date of cancer diagnosis in older persons and peaks in the 30 days before.

Comparative Performance of Clinical Risk Assessment Models for Hospital-Acquired Venous Thromboembolism in Medical Patients.

BACKGROUND: Improved thromboprophylaxis for acutely ill medical patients relies on valid predictions of thrombotic risks. Our aim was to compare the performance of the Improve and Geneva clinical risk assessment models (RAMs), and to simplify the current Geneva RAM. METHODS: Medical inpatients from eight Swiss hospitals were prospectively followed during 90 days, for symptomatic venous thromboembolism (VTE) or VTE-related death. We compared discriminative performance and calibration of the RAMs, using time-to-event methods with competing risk modelling of non-VTE death. RESULTS: In 1,478 patients, the 90-day VTE cumulative incidence was 1.6%. Discrimination of the Improve and Geneva RAM was similar, with a 30-day AUC (areas under the curve) of 0.78 (95% CI [confidence interval]: 0.65-0.92) and 0.81 (0.73-0.89), respectively. According to the Improve RAM, 68% of participants were at low risk (0.8% VTE at 90 days), and 32% were at high risk (4.7% VTE), with a sensitivity of 73%. According to the Geneva RAM, 35% were at low risk (0.6% VTE) and 65% were at high risk (2.8% VTE), with a sensitivity of 90%. Among patients without thromboprophylaxis, the sensitivity was numerically greater in the Geneva RAM (85%) than in the Improve RAM (54%). We derived a simplified Geneva RAM with comparable discrimination and calibration as the original Geneva RAM. CONCLUSIONS: We found comparably good discrimination of the Improve and Geneva RAMs. The Improve RAM classified more patients as low risk, but with possibly lower sensitivity and greater VTE risks, suggesting that a lower threshold for low risk (<2) should be used. The simplified Geneva RAM may represent an alternative to the Geneva RAM with enhanced usability.

Rivaroxaban vs. warfarin on extended deep venous thromboembolism treatment: A cost analysis.

Background Standard treatment for deep venous thromboembolism involves parenteral anticoagulation overlapping with a vitamin K antagonist, an approach that is effective but associated with limitations including the need for frequent coagulation monitoring. The direct oral anticoagulant rivaroxaban is similarly effective to standard therapy as a single-drug treatment for venous thromboembolism and does not require routine coagulation monitoring. The aim of this analysis was to project the long-term costs and outcomes for rivaroxaban compared to standard of care (tinzaparin/warfarin). Methods A total of 184 patients who were under anticoagulant therapy with warfarin or rivaroxaban for extended deep venous thromboembolism were retrospectively evaluated; 59 received rivaroxaban and 125 received warfarin therapy. Assessments were made on age, gender, place of residence, the duration of anticoagulation, mean international normalized ratio value, the effective rate of international normalized ratio (time in the therapeutic range), bleeding-related complication rate, duration of hospitalization due to complications, the number of annual outpatient department admission, cost for drug, cost for hospitalization, cost for outpatient department admission and international normalized ratio measurements. Results The annual outpatient cost is higher in warfarin group (147.09 ± 78 vs. 62.32 ± 19.79 USD p < 0.001). But annual drug cost is higher in rivaroxaban group (362.6 vs. 71.55 ± 31.01 USD p < 0.001). Overall cost of rivaroxaban group is higher than warfarin group (476.25 ± 36.78 vs. 364.82 ± 174.44 USD). Warfarin is not cost-effective when non-drug costs (342.5 ± 174.44 vs. 113.65 ± 36.77) and hospital costs (173.85 ± 122.73 vs. 64.9 ± 23.55 USD) were analyzed. Conclusion This analysis suggests that rivaroxaban has lower costs than warfarin in terms of outpatient department admission and hospital costs due to complications; however, warfarin was more economic when all cost parameters were considered. Time in the therapeutic range was found as 56% for warfarin that should be taken into account while analyzing costs and benefits.

Atrial fibrillation in New Zealand primary care: Prevalence, risk factors for stroke and the management of thromboembolic risk.

Background Atrial fibrillation is a major risk factor for stroke and heart disease but there is limited information on its prevalence in New Zealand primary care or the treatment provided to manage thromboembolic risk. Our aim was to estimate the prevalence of atrial fibrillation, assess patient risk for thromboembolism and evaluate the appropriateness of risk reduction using antiplatelet and oral anticoagulation therapy. Design A retrospective cohort study utilising electronic medical records for 739,000 patients registered with 170 general practices in 2014. Methods Patient diagnoses and prescriptions from 2010-2014 were analysed to identify patients with atrial fibrillation in 2014 and co-morbidities included in the CHA2DS2-VASc algorithm. Adjusted prevalence of atrial fibrillation by patient demographic group and the proportion of patients following recommended antithrombotic therapy were calculated. Results 12,712 patients were identified with AF (1.72%, 95% confidence interval 1.69%-1.75%). Prevalence was significantly higher for Maori (odds ratio 1.91, 95% confidence interval 1.80-2.03) than Europeans after adjusting for age, sex, deprivation and clinical risk factors. Stroke risk for Maori and Pacific Island patients was higher than for Europeans across all age groups. Of the 10,406 patients (81.9%) at high risk for thromboembolism, 60.5% were using anticoagulants, 24.1% aspirin monotherapy and 15.4% neither anticoagulants nor aspirin. Oral anticoagulants were used by 31.5% of patients at low risk (CHA2DS2-VASc <2). Conclusions Oral anticoagulants are under-utilised in the management of thromboembolic risk in high risk patients with atrial fibrillation. Better promotion of guideline recommendations for the treatment of patients with atrial fibrillation may be required to improve clinician and patient decision-making.

Modelling projections for the uptake of edoxaban in an European population to 2050: effects on stroke, thromboembolism, and health economics perspectives.

AIMS: In the coming decades, the number of Europeans with atrial fibrillation (AF) is set to rise as the population ages, and so with it will the number of strokes. The risk of thromboembolism (principally stroke and systemic embolism) and death can be reduced by the use of the vitamin K antagonists (VKA, e.g. warfarin) and more so by non-VKA oral anticoagulants (NOACs) such as edoxaban. METHODS AND RESULTS: We modelled the effect of the increasing use of edoxaban in preference to warfarin in a European AF population from both clinical and economic perspectives. We estimate that the introduction of NOACs in 2010 eliminated over 88 000 thromboembolisms and deaths annually, of which over 17 000 were ischaemic strokes. At a 1-year cost of €30k per ischaemic stroke, this strategy saved €510 million annually. Should the use of edoxaban increase from 11% in 2013 to 75% by 2030, we expect that rate of thromboembolism and death will fall from 5.67 to 5.42 total events per million patients per year, which will further eliminate over 12 000 of these events annually. At an inflation-adjusted 1-year cost of approximately €35k per ischaemic stroke, this will save €44.5 million each year. At a conservative rate of increase in the AF population of 2.2-fold from 2005, in 2050 there will be around 180 000 AF-related ischaemic strokes that, at an inflation-adjusted cost of around €62k per stroke, sums to €11 116 million. Should the rate of AF rise 2.6-fold from 2005, then in 2050 there will be 214 500 ischaemic strokes that will cost around €13 300 million. CONCLUSION: Our data point to a substantial increase in the human and economic cost burden of AF and so emphasize the need to reduce this burden. This may be achieved by the increased use of oral anticoagulants, particularly with the NOACs such as edoxaban.

Left atrial appendage morphology assessment for risk stratification of embolic stroke in patients with atrial fibrillation: A meta-analysis.

BACKGROUND: Thromboembolic event (TE) risk stratification is performed by using CHA2DS2VASc score. It has been suggested that left atrial appendage (LAA) morphology independently influences TE risk in patients with nonvalvular atrial fibrillation. LAA morphology has been classified into 4 types: chicken wing, cauliflower, windsock, and cactus. OBJECTIVE: The purpose of this study was to determine TE risk for each LAA morphology in patients with atrial fibrillation with low to intermediate TE risk. METHODS: A systematic review of MEDLINE, Cochrane Library, and Embase for studies that used computed tomography, tridimensional transesophageal echocardiography, and cardiac magnetic resonance imaging to categorize the LAA morphologies with assessment of TE prevalence. Odds ratio (OR) and 95% confidence intervals (CIs) were measured using the Mantel-Haenszel method. The fixed effects model was used, and if heterogeneity (I2) was >25%, effects were analyzed using a random model. RESULTS: Eight studies with 2596 patients were included. Eighty-four percent (n=1872) of patients had a CHADS2 score of <2. TE risk was lower in chicken wing morphology than in non-chicken wing morphology (OR 0.46; 95% CI 0.36-0.58). Likewise, chicken wing morphology had lower TE risk than did other morphologies (chicken wing vs cauliflower: OR 0.38; 95% CI 0.26-0.56; chicken wing vs windsock: OR 0.48; 95% CI 0.31-0.73; chicken wing vs cactus: OR 0.49; 95% CI 0.36-0.66). CONCLUSION: Patients with chicken wing LAA morphology are less likely to develop TE than patients with non-chicken wing morphology. LAA morphology may be a valuable criterion in predicting TE and could affect the stratification and anticoagulation management of patients with low to intermediate TE risk.

Assessment of coagulation utilizing thromboelastometry in dogs undergoing orthopedic surgery.

OBJECTIVE: To evaluate blood coagulation using thromboelastometry in dogs following orthopedic surgery. DESIGN: Longitudinal observational study. SETTING: University veterinary teaching hospital. ANIMALS: Thirty-four adult client-owned dogs. MEASUREMENTS AND MAIN RESULTS: Dogs undergoing elective or emergency orthopedic surgery had whole blood collected before (T0), at 24 hours (T1), and 1 week (T2) after surgery. Whole blood from each dog was collected by jugular venipuncture using a 20-Ga needle and minimum venous stasis. The blood was placed into tubes containing 3.8% trisodium citrate (1 part citrate: 9 parts blood) and rested at 37°C. Coagulation was evaluated by means of thromboelastometry using the in-TEM, ex-TEM, and fib-TEM assays. Statistically significant increases (P < 0.05) in maximum clot firmness (MCF) from T0 to T1 in the in-TEM and fib-TEM profiles (both P = 0.0001), from T0 to T2 in the in-TEM, ex-TEM, and fib-TEM profiles (P = 0.012, P = 0.037, and P = 0.0001, respectively), and from T1 to T2 in the fib-TEM profile (P = 0.039) were noted. The α angle increased from T0 to T2 in the in-TEM and ex-TEM profiles (P = 0.019 and P = 0.036, respectively). All results were, however, within the institutional reference ranges. CONCLUSIONS: In this study, unlike the hypercoagulability observed in human orthopedic patients, a hypercoagulable state as measured by thromboelastometry did not develop in dogs following orthopedic surgery.

Growth differentiation factor 15, a marker of oxidative stress and inflammation, for risk assessment in patients with atrial fibrillation: insights from the Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial.

BACKGROUND: Growth differentiation factor 15 (GDF-15), high-sensitivity troponin, and N-terminal pro-brain natriuretic peptide levels are predictive of death and cardiovascular events in healthy elderly subjects, patients with acute coronary syndrome, and patients with heart failure. High-sensitivity troponin I and N-terminal pro-brain natriuretic peptide are also prognostic in patients with atrial fibrillation. We evaluated the prognostic value of GDF-15 alone and in addition to clinical characteristics and other biomarkers in patients with atrial fibrillation. METHODS AND RESULTS: The Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation (ARISTOTLE) trial randomized 18 201 patients with atrial fibrillation to apixaban or warfarin. Biomarkers were measured at randomization in 14 798 patients. Efficacy and safety outcomes during 1.9 years of follow-up were compared across quartiles of GDF-15 by use of Cox analyses adjusted for clinical characteristics, randomized treatment, and other biomarkers. The GDF-15 level showed a median of 1383 ng/L (interquartile range, 977-2052 ng/L). Annual rates of stroke or systemic embolism ranged from 0.9% to 2.03% (P<0.001); of major bleeding, from 1.22% to 4.53% (P<0.001); and of mortality, from 1.34% to 7.19% (P<0.001) in the lowest compared with the highest GDF-15 quartile. The prognostic information provided by GDF-15 was independent of clinical characteristics and clinical risk scores. Adjustment for the other cardiac biomarkers attenuated the prognostic value for stroke, whereas the prognostic value for mortality and major bleeding remained. Apixaban consistently reduced stroke, mortality, and bleeding, regardless of GDF-15 levels. CONCLUSIONS: GDF-15 is a risk factor for major bleeding, mortality, and stroke in atrial fibrillation. The prognostic value for major bleeding and death remained even in the presence of N-terminal pro-brain natriuretic peptide and high-sensitivity troponin I. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00412984.

Assessment of platelet function with light transmission aggregometry in 24 patients supported with a continuous-flow left ventricular assist device: a single-center experience.

OBJECTIVES: This study evaluated platelet function for an extended period of time in patients with a HeartMate II continuous-flow left ventricular assist device (Thoratec Corporation, Pleasanton, Calif) with light transmission aggregometry and investigated the potential role of this test in clinical management. METHODS: Twenty-four patients were studied prospectively after implantation. Mean duration of support was 8.5 months. Platelet functions were assessed with light transmission aggregometry induced by thrombin receptor agonist peptide, ristocetin, or arachidonic acid. All patients received an aspirin regimen that was progressively increased until arachidonic acid-triggered platelet aggregation dropped lower than 20%. Plasma levels of von Willebrand factor were also determined when ristocetin-induced platelet agglutination was impaired. RESULTS: Intensity of platelet aggregation with thrombin receptor agonist peptide was little changed in patients with a HeartMate II relative to control subjects. Aspirin dose greater than 160 mg/d was progressively required in 46% of patients. Ristocetin-induced platelet agglutination was impaired in 4 patients in association with a lack of high molecular weight von Willebrand factor multimers. Three patients had thromboembolic events (12.5%) and 8 (33%) suffered from major bleeding complications. CONCLUSIONS: High platelet reactivity during treatment with aspirin is common in patients with a HeartMate II. Moreover, light transmission aggregometry may detect impaired ristocetin-induced platelet agglutination, enabling dosage of aspirin to be adjusted. Our strategy showed no major improvements in terms of thrombosis rate when compared with published data, although bleeding frequency was somewhat reduced. Benefits of light transmission aggregometry testing need to be assessed in a larger randomized study with a longer follow-up.

Hospital readmissions: necessary evil or preventable target for quality improvement.

OBJECTIVES: To evaluate readmission rates and associated factors to identify potentially preventable readmissions. BACKGROUND: The decision to penalize hospitals for readmissions is compelling health care systems to develop processes to minimize readmissions. Research to identify preventable readmissions is critical to achieve these goals. METHODS: We performed a retrospective review of University HealthSystem Consortium database for cancer patients hospitalized from January 2010 to September 2013. Outcome measures were 7-, 14-, and 30-day readmission rates and readmission diagnoses. Hospital and disease characteristics were evaluated to evaluate relationships with readmission. RESULTS: A total of 2,517,886 patients were hospitalized for cancer treatment. Readmission rates at 7, 14, and 30 days were 2.2%, 3.7%, and 5.6%, respectively. Despite concern that premature hospital discharge may be associated with increased readmissions, a shorter initial length of stay predicted lower readmission rates. Furthermore, high-volume centers and designated cancer centers had higher readmission rates. Evaluating institutional data (N = 2517 patients) demonstrated that factors associated with higher readmission rates include discharge from a medical service, site of malignancy, and emergency primary admission. When examining readmission within 7 days for surgical services, the most common readmission diagnoses were infectious causes (46.3%), nausea/vomiting/dehydration (26.8%), and pain (6.1%). CONCLUSIONS: A minority of patients after hospitalization for cancer-related therapy are readmitted with potentially preventable conditions such as nausea, vomiting, dehydration, and pain. However, most factors associated with readmission cannot be modified. In addition, high-volume centers and designated cancer centers have higher readmission rates, which may indicate that readmission rates may not be an appropriate marker for quality improvement.

Does periprocedural anticoagulation management of atrial fibrillation affect the prevalence of silent thromboembolic lesion detected by diffusion cerebral magnetic resonance imaging in patients undergoing radiofrequency atrial fibrillation ablation with open irrigated catheters? Results from a prospective multicenter study.

BACKGROUND: Silent cerebral ischemia (SCI) has been reported in 14% of cases after catheter ablation of atrial fibrillation (AF) with radiofrequency (RF) energy and discontinuation of warfarin before AF ablation procedures. OBJECTIVE: The purpose of this study was to determine whether periprocedural anticoagulation management affects the incidence of SCI after RF ablation using an open irrigated catheter. METHODS: Consecutive patients undergoing RF ablation for AF without warfarin discontinuation and receiving heparin bolus before transseptal catheterization (group I, n = 146) were compared with a group of patients who had protocol deviation in terms of maintaining the therapeutic preprocedural international normalized ratio (patients with subtherapeutic INR) and/or failure to receive pretransseptal heparin bolus infusion and/or ≥2 consecutive ACT measurements <300 seconds (noncompliant population, group II, n = 134) and with a group of patients undergoing RF ablation with warfarin discontinuation bridged with low molecular weight heparin (group III, n = 148). All patients underwent preablation and postablation (within 48 hours) diffusion magnetic resonance imaging. RESULTS: SCI was detected in 2% of patients (3/146) in group I, 7% (10/134) in group II, and 14% (21/148) in group III (P <.001). "Therapeutic INR" was strongly associated with a lower prevalence of postprocedural silent cerebral ischemia (SCI). Multivariable analysis demonstrated nonparoxysmal AF (odds ratio 3.8, 95% confidence interval 1.5-9.7, P = .005) and noncompliance to protocol (odds ratio 2.8, 95% confidence interval 1.5-5.1, P <.001] to be significant predictors of ischemic events. CONCLUSION: Strict adherence to an anticoagulation protocol significantly reduces the prevalence of SCI after catheter ablation of AF with RF energy.

Cardioembolic stroke: practical considerations for patient risk management and secondary prevention.

Cardioembolic (CE) stroke constitutes approximately 20% of all occurrence of ischemic stroke in patients. Atrial fibrillation remains the most common and most studied mechanism underlying CE stroke events. Cardioembolic strokes carry high morbidity and are associated with early recurrence in patients. Our understanding of other patient mechanisms associated with CE stroke, including valvular disease, left ventricular dysfunction, and patent foramen ovale, continues to grow. Our review summarizes the diagnosis and management of patients who have sustained CE stroke as a result of the aforementioned cardiac mechanisms. Advances in primary and secondary risk management for prevention of CE stroke are also highlighted in our article-specifically, emerging data regarding monitoring of patients with atrial fibrillation, new anticoagulation therapy, and management of patients with decreased ejection fraction.

Application of the Caprini risk assessment model in evaluation of non-venous thromboembolism complications in plastic and reconstructive surgery patients.

BACKGROUND: The Caprini Risk Assessment Model is used to categorize patient risk for venous thromboembolism (VTE) events; its predictive associations have been repeatedly corroborated. Calculating scores involves consideration of systemic factors that may predict other postoperative complications. OBJECTIVE: This study investigates whether Caprini scores can be applied to non-VTE complications. METHODS: The authors undertook a retrospective chart review of 1598 encounters for a series of complex reconstructive and body contouring operations at an academic medical institution. Input variables included Caprini score components, patient comorbidities, and prophylactic use of antithrombotic drugs. Output variables were postoperative complications. Tests for proportions were performed on percentile data. Nonpercentile data were treated with comparison of means (t test). Odds ratios for complications were calculated for stratified risk groups and compared. RESULTS: The overall complication rate was 28.03%. Deep vein thrombosis (DVT) incidence was 1.50%. Differences in age, body mass index (BMI), operation time, hypertension, diabetes, renal disease, and cancer were statistically significant between patients who experienced complications and those who did not. For DVT versus DVT-free patients, differences in sex, BMI, operation time, smoking status, diabetes, hypertension, and prior DVT were significant. Caprini scores identified 628 encounters as low risk (0-4) and 970 as high risk (>5). Dehiscence, infection, necrosis, seroma, hematoma, and overall complication rate significantly increased the incidence for the high-risk group. CONCLUSIONS: Caprini scores can be used as valuable predictors for some non-VTE postoperative complications (dehiscence, infection, seroma, hematoma, and necrosis). In addition to VTE events, clinicians should pay special attention to clinical signs indicative of the complications listed above when dealing with high-risk, high-Caprini score patients.

Avaliação da estabilidade de anticoagulação entre a Varfarina e a Femprocumona / Oral anticoagulation stability assessment with Warfarin and Phenprocoumon

Fundamentos: A varfarina e a femprocumona são os anticoagulantes orais mais utilizados; no entanto, até então, não existem estudos randomizados comparando a estabilidade da anticoagulação entre estes dois fármacos. Objetivos: Comparar a varfarina e femprocumona quanto à estabilidade na manutenção de anticoagulação em nível terapêutico (razão normatizada internacional [RNI] entre 2,0 e 3,0) e avaliar a incidência de complicações hemorrágicas e tromboembólicas decorrentes de anticoagulação inadequada.Métodos: Ensaio clínico, randomizado, duplo-cego, incluindo pacientes em tratamento vigente com anticoagulante oral, porém com RNI abaixo do alvo terapêutico nas últimas três semanas, randomizados para uso de varfarina ou femprocumona. O ajuste da dose da medicação foi realizado conforme algoritmo pré-estabelecido. Resultados: Foram randomizados 62 pacientes, sendo 31 em cada grupo, durante as cinco primeiras semanas de estudo. Verificou-se que a femprocumona se mostrou mais instável comparada à varfarina. A partir da sexta aferição de RNI, o grupo femprocumona apresentou melhora na estabilidade do valor do RNI, porém não houve significância estatística. Também não houve diferença significativa em relação aos efeitos colaterais dos fármacos. Conclusão: A varfarina demonstrou maior eficácia na estabilidade do RNI em relação à femprocumona.

Background: Although warfarin and phenprocoumon are the most widely used oral anticoagulants, there a r e n o r a n d o m i z e d s t u d i e s c o m p a r i n g t h e anticoagulation stability of these two drugs.Objectives: To compare warfarin and phenprocoumon in terms of therapeutic anticoagulation maintenance stability (international normalized ratio [INR] between 2.0 and 3.0) and evaluate the incidence of thromboembolic and hemorrhagic complications arising from inadequate anticoagulation.Methods: Randomized double-blind clinical trial with patients undergoing current oral anticoagulant treatment but with INR below the therapeutic target during the past 3 weeks, randomized for warfarin or phenprocoumon. Medication dosages were adjusted in compliance with a predetermined algorithm.Results: With 62 patients randomized into two groups of 31 each during the first five weeks of the study, phenprocoumon was found to be more unstable than warfarin. From the sixth INR measurement onwards, the stability of the INR value improved in the phenprocoumon group, but with no statistical significance. There were no significant differences in the side effects of the drugs.Conclusion: Warfarin demonstrated greater effectiveness for INR stability than phenprocoumon.