Outpatient treatment of low-risk venous thromboembolism with monotherapy oral anticoagulation: patient quality of life outcomes and clinician acceptance

BACKGROUND: Oral monotherapy anticoagulation has facilitated home treatment of venous thromboembolism (VTE) in outpatients. OBJECTIVES: The aim of this study was to measure efficacy, safety, as well as patient and physician perceptions produced by a protocol that selected VTE patients as low-risk patients by the Hestia criteria, and initiated home anticoagulation with an oral factor Xa antagonist. METHODS: Patients were administered the Venous Insufficiency Epidemiological and Economic Study Quality of life/Symptoms questionnaire [VEINEs QoL/Sym] and the physical component summary [PCS] from the Rand 36-Item Short Form Health Survey [SF36]). The primary outcomes were VTE recurrence and hemorrhage at 30 days. Secondary outcomes compared psychometric test scores between patients with deep vein thrombosis (DVT) to those with pulmonary embolism (PE). Patient perceptions were abstracted from written comments and physician perceptions specific to PE outpatient treatment obtained from structured survey. RESULTS: From April 2013 to September 2015, 253 patients were treated, including 67 with PE. Within 30 days, 2/253 patients had recurrent DVT and 2/253 had major hemorrhage; all four had DVT at enrollment. The initial PCS scores did not differ between DVT and PE patients (37.2±13.9 and 38.0±12.1, respectively) and both DVT and PE patients had similar improvement over the treatment period (42.2±12.9 and 43.4±12.7, respectively), consistent with prior literature. The most common adverse event was menorrhagia, present in 15% of women. Themes from patient-written responses reflected satisfaction with increased autonomy. Physicians' (N=116) before-to-after protocol comfort level with home treatment of PE increased 48% on visual analog scale. CONCLUSION: Hestia-negative VTE patients treated with oral monotherapy at home had low rates of VTE recurrence and bleeding, as well as quality of life measurements similar to prior reports

Implementation and preliminary clinical outcomes of a pharmacist-managed venous thromboembolism clinic for patients treated with rivaroxaban post emergency department discharge

Objective To describe the implementation, work flow, and differences in outcomes between a pharmacist-managed clinic for the outpatient treatment of venous thromboembolism (VTE) using rivaroxaban versus care by a primary care provider. Interventions Patients in the studied health system that are diagnosed with low-risk VTE in the emergency department are often discharged without hospital admission. These patients are treated with rivaroxban and follow up either in a pharmacist-managed VTE clinic or with their primary care provider. Pharmacists in the VTE clinic work independently under a collaborative practice agreement. An evaluation of thirty-four patients, seventeen in each treatment arm, was conducted to compare the differences in treatment-related outcomes of rivaroxaban when managed by a pharmacist versus a primary care provider. Results The primary endpoint was a six month composite of anticoagulation treatment-related complications that included a diagnosis of major bleeding, recurrent thromboembolism, or fatality due to either major bleeding or recurrent thromboembolism. Secondary endpoints included number of hospitalizations, adverse events, and medication adherence. There was no difference in the primary endpoint between groups with one occurrence of the composite endpoint in each treatment arm (p=1.000), both of which were recurrent thromboembolic events. Medication adherence assessment was formally performed in 8 patients in the pharmacist group versus 0 patients in the control group. No differences were seen amongst other secondary endpoints. Conclusions The pharmacist-managed clinic is a novel expansion of clinical pharmacy services that treats patients with low-risk VTEs with rivaroxaban in the outpatient setting. The evaluation of outcomes provides support that pharmacist-managed care utilizing standardized protocols under a collaborative practice agreement may be as safe as care by a primary care provider

Independent evaluation of a simple clinical prediction rule to identify right ventricular dysfunction in patients with shortness of breath

BACKGROUND: Many patients have unexplained persistent dyspnea after negative computed tomographic pulmonary angiography (CTPA). We hypothesized that many of these patients have isolated right ventricular (RV) dysfunction from treatable causes. We previously derived a clinical decision rule (CDR) for predicting RV dysfunction consisting of persistent dyspnea and normal CTPA, finding that 53% of CDR-positive patients had isolated RV dysfunction. Our goal is to validate this previously derived CDR by measuring the prevalence of RV dysfunction and outcomes in dyspneic emergency department patients. METHODS: A secondary analysis of a prospective observational multicenter study that enrolled patients presenting with suspected PE was performed. We included patients with persistent dyspnea, a nonsignificant CTPA, and formal echo performed. Right ventricular dysfunction was defined as RV hypokinesis and/or dilation with or without moderate to severe tricuspid regurgitation. RESULTS: A total of 7940 patients were enrolled. Two thousand six hundred sixteen patients were analyzed after excluding patients without persistent dyspnea and those with a significant finding on CTPA. One hundred ninety eight patients had echocardiography performed as standard care. Of those, 19% (95% confidence interval [CI], 14%-25%) and 33% (95% CI, 25%-42%) exhibited RV dysfunction and isolated RV dysfunction, respectively. Patients with isolated RV dysfunction or overload were more likely than those without RV dysfunction to have a return visit to the emergency department within 45 days for the same complaint (39% vs 18%; 95% CI of the difference, 4%-38%). CONCLUSION: This simple clinical prediction rule predicted a 33% prevalence of isolated RV dysfunction or overload. Patients with isolated RV dysfunction had higher recidivism rates and a trend toward worse outcomes

Effect of metabolic syndrome on mean pulmonary arterial pressures in patients with acute pulmonary embolism treated with catheter-directed thrombolysis

Background: Metabolic syndrome (MetS) has been associated with a procoagulant and hypofibrinolytic state. Current data exploring the role of MetS in venous thromboembolism (VTE) are limited. The objective was to measure the prevalence of MetS in patients with acute PE receiving catheter-directed thrombolysis (CDT) and to investigate its effect on mean pulmonary arterial pressure and overall treatment success. Methods: We used a 3-year prospective registry of ED patients with acute PE with severity qualifying for activation of a PE response team (PERT). All patients had CDT with catheter-measured mPAP and angiography. The presence or absence of MetS components were extracted from chart review based on the following criteria: 1. body mass index (BMI) >30 kg/m2; 2. diagnosed hypertension; 3. diabetes mellitus (including HbA1c >6.5%) and; 4. dyslipidemia (including triglycerides >150 mg/dL or high-density lipoprotein <40 mg/dL). Results: Of the 134 patients, 85% met the criteria for at least one of four MetS components, with obesity being most common, present in 71%. Results demonstrated a positive concordance between the number of criteria for MetS and MPAP, both pre- and post-fibrinolysis, as pressures tended to increase with each additional MetS criterion. Multivariate regression analysis determined age (-), BMI (+) and hypertension (+) to be significant independent predictor variables for mPAP. Conclusions: MetS was common in patients with more severe manifestations of PE and was associated with higher mPAP values both at diagnosis and following treatment with CDT

Factors Associated With Positive D-dimer Results in Patients Evaluated for Pulmonary Embolism

Objectives:  Available D-dimer assays have low specificity and may increase radiographic testing for pulmonary embolism (PE). To help clinicians better target testing, this study sought to quantify the effect of risk factors for a positive quantitative D-dimer in patients evaluated for PE. Methods:  This was a prospective, multicenter, observational study. Emergency department (ED) patients evaluated for PE with a quantitative D-dimer were eligible for inclusion. The main outcome of interest was a positive D-dimer. Odds ratio (ORs) and 95% confidence intervals (CIs) were determined by multivariable logistic regression. Adjusted estimates of relative risk were also calculated. Results:  A total of 4,346 patients had D-dimer testing, of whom 2,930 (67%) were women. A total of 2,500 (57%) were white, 1,474 (34%) were black or African American, 238 (6%) were Hispanic, and 144 (3%) were of other race or ethnicity. The mean (±SD) age was 48 (±17) years. Overall, 1,903 (44%) D-dimers were positive. Model fit was adequate (c-statistic = 0.739, Hosmer and Lemeshow p-value = 0.13). Significant positive predictors of D-dimer positive included female sex; increasing age; black (vs. white) race; cocaine use; general, limb, or neurologic immobility; hemoptysis; hemodialysis; active malignancy; rheumatoid arthritis; lupus; sickle cell disease; prior venous thromboembolism (VTE; not under treatment); pregnancy and postpartum state; and abdominal, chest, orthopedic, or other surgery. Warfarin use was protective. In contrast, several variables known to be associated with PE were not associated with positive D-dimer results: body mass index (BMI), estrogen use, family history of PE, (inactive) malignancy, thrombophilia, trauma within 4 weeks, travel, and prior VTE (under treatment). Conclusions:  Many factors are associated with a positive D-dimer test. The effect of these factors on the usefulness of the test should be considered prior to ordering a D-dimer

Evaluation of Pulmonary Embolism in the Emergency Department and Consistency With a National Quality Measure: Quantifying the opportunity for improvement

Background The National Quality Forum (NQF) has endorsed a performance measure designed to increase imaging efficiency for the evaluation of pulmonary embolism (PE) in the emergency department (ED). To our knowledge, no published data have examined the effect of patient-level predictors on performance. Methods To quantify the prevalence of avoidable imaging in ED patients with suspected PE, we performed a prospective, multicenter observational study of ED patients evaluated for PE from 2004 through 2007 at 11 US EDs. Adult patients tested for PE were enrolled, with data collected in a standardized instrument. The primary outcome was the proportion of imaging that was potentially avoidable according to the NQF measure. Avoidable imaging was defined as imaging in a patient with low pretest probability for PE, who either did not have a D-dimer test ordered or who had a negative D-dimer test result. We performed subanalyses testing alternative pretest probability cutoffs and imaging definitions on measure performance as well as a secondary analysis to identify factors associated with inappropriate imaging. χ2 Test was used for bivariate analysis of categorical variables and multivariable logistic regression for the secondary analysis. Results We enrolled 5940 patients, of whom 4113 (69%) had low pretest probability of PE. Imaging was performed in 2238 low-risk patients (38%), of whom 811 had no D-dimer testing, and 394 had negative D-dimer test results. Imaging was avoidable, according to the NQF measure, in 1205 patients (32%; 95% CI, 31%-34%). Avoidable imaging owing to not ordering a D-dimer test was associated with age (odds ratio [OR], 1.15 per decade; 95% CI, 1.10-1.21). Avoidable imaging owing to imaging after a negative D-dimer test result was associated with inactive malignant disease (OR, 1.66; 95% CI, 1.11-2.49). Conclusions One-third of imaging performed for suspected PE may be categorized as avoidable. Improving adherence to established diagnostic protocols is likely to result in significantly fewer patients receiving unnecessary irradiation and substantial savings

Randomized Controlled Trial of Mechanical Thrombectomy Versus Catheter-directed Thrombolysis for Acute Hemodynamically Stable Pulmonary Embolism: Rationale and Design of the PEERLESS Study.

BACKGROUND The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient's care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the Pulmonary Embolism Response Team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and non-thrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a non-randomized MT cohort for separate analysis. The primary endpoint will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: 1) all-cause mortality, 2) intracranial hemorrhage, 3) major bleeding, 4) clinical deterioration and/or escalation to bailout, and 5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary endpoints. Other key secondary endpoints include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS PEERLESS is the first RCT to compare two different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted

2-Hour Accelerated Diagnostic Protocol to Assess Patients With Chest Pain Symptoms Using Contemporary Troponins as the Only Biomarker

Objectives The purpose of this study was to determine whether a new accelerated diagnostic protocol (ADP) for possible cardiac chest pain could identify low-risk patients suitable for early discharge (with follow-up shortly after discharge). Background Patients presenting with possible acute coronary syndrome (ACS), who have a low short-term risk of adverse cardiac events may be suitable for early discharge and shorter hospital stays. Methods This prospective observational study tested an ADP that included pre-test probability scoring by the Thrombolysis In Myocardial Infarction (TIMI) score, electrocardiography, and 0 + 2 h values of laboratory troponin I as the sole biomarker. Patients presenting with chest pain due to suspected ACS were included. The primary endpoint was major adverse cardiac event (MACE) within 30 days. Results Of 1,975 patients, 302 (15.3%) had a MACE. The ADP classified 392 patients (20%) as low risk. One (0.25%) of these patients had a MACE, giving the ADP a sensitivity of 99.7% (95% confidence interval [CI]: 98.1% to 99.9%), negative predictive value of 99.7% (95% CI: 98.6% to 100.0%), specificity of 23.4% (95% CI: 21.4% to 25.4%), and positive predictive value of 19.0% (95% CI: 17.2% to 21.0%). Many ADP negative patients had further investigations (74.1%), and therapeutic (18.3%) or procedural (2.0%) interventions during the initial hospital attendance and/or 30-day follow-up. Conclusions Using the ADP, a large group of patients was successfully identified as at low short-term risk of a MACE and therefore suitable for rapid discharge from the emergency department with early follow-up. This approach could decrease the observation period required for some patients with chest pain. (An observational study of the diagnostic utility of an accelerated diagnostic protocol using contemporary central laboratory cardiac troponin in the assessment of patients presenting to two Australasian hospitals with chest pain of possible cardiac origin; ACTRN12611001069943

Randomized Controlled Trial of Mechanical Thrombectomy vs Catheter-Directed Thrombolysis for Acute Hemodynamically Stable Pulmonary Embolism: Rationale and Design of the PEERLESS Study

BACKGROUND: The identification of hemodynamically stable pulmonary embolism (PE) patients who may benefit from advanced treatment beyond anticoagulation is unclear. However, when intervention is deemed necessary by the PE patient\u27s care team, data to select the most advantageous interventional treatment option are lacking. Limiting factors include major bleeding risks with systemic and locally delivered thrombolytics and the overall lack of randomized controlled trial (RCT) data for interventional treatment strategies. Considering the expansion of the pulmonary embolism response team (PERT) model, corresponding rise in interventional treatment, and number of thrombolytic and nonthrombolytic catheter-directed devices coming to market, robust evidence is needed to identify the safest and most effective interventional option for patients. METHODS: The PEERLESS study (ClinicalTrials.gov identifier: NCT05111613) is a currently enrolling multinational RCT comparing large-bore mechanical thrombectomy (MT) with the FlowTriever System (Inari Medical, Irvine, CA) vs catheter-directed thrombolysis (CDT). A total of 550 hemodynamically stable PE patients with right ventricular (RV) dysfunction and additional clinical risk factors will undergo 1:1 randomization. Up to 150 additional patients with absolute thrombolytic contraindications may be enrolled into a nonrandomized MT cohort for separate analysis. The primary end point will be assessed at hospital discharge or 7 days post procedure, whichever is sooner, and is a composite of the following clinical outcomes constructed as a hierarchal win ratio: (1) all-cause mortality, (2) intracranial hemorrhage, (3) major bleeding, (4) clinical deterioration and/or escalation to bailout, and (5) intensive care unit admission and length of stay. The first 4 components of the win ratio will be adjudicated by a Clinical Events Committee, and all components will be assessed individually as secondary end points. Other key secondary end points include all-cause mortality and readmission within 30 days of procedure and device- and drug-related serious adverse events through the 30-day visit. IMPLICATIONS: PEERLESS is the first RCT to compare 2 different interventional treatment strategies for hemodynamically stable PE and results will inform strategy selection after the physician or PERT determines advanced therapy is warranted

Comparison of isoflurane and α-chloralose in an anesthetized swine model of acute pulmonary embolism producing right ventricular dysfunction

Pulmonary embolism (PE) is a leading cause of sudden cardiac death, and a model is needed for testing potential treatments. In developing a model, we compared the hemodynamic effects of isoflurane and α-chloralose in an acute swine model of PE because the choice of anesthesia will likely affect the cardiovascular responses of an animal to PE. At baseline, swine that received α-chloralose (n = 6) had a lower heart rate and cardiac output and higher SpO2, end-tidal CO2, and mean arterial pressure than did those given isoflurane (n = 9). After PE induction, swine given α-chloralose compared with isoflurane exhibited a lower heart rate (63 ± 10 compared with 116 ± 15 bpm) and peripheral arterial pressure (52 ± 12 compared with 61 ± 12 mm Hg); higher SpO2 (98% ± 3% compared with 95% ± 1%), end-tidal CO2 (35 ± 4 compared with 32 ± 5), and systolic blood pressure (121 ± 8 compared with 104 ± 20 mm Hg); and equivalent right ventricular:left ventricular ratios (1.32 ± 0.50 compared with 1.23 ± 0.19) and troponin I mean values (0.09 ± 0.07 ng/mL compared with 0.09 ± 0.06 ng/mL). Isoflurane was associated with widely variable fibrinogen and activated partial thromboplastin time. Intraexperiment mortality was 0 of 6 animals for α-chloralose and 2 of 9 swine for isoflurane. All swine anesthetized with α-chloralose survived with sustained pulmonary hypertension, RV-dilation-associated cardiac injury without the confounding vasodilatory or coagulatory effects of isoflurane. These data demonstrate the physiologic advantages of α-chloralose over isoflurane for anesthesia in a swine model of severe submassive PE