Outpatient Anticoagulation Research Articles

Outpatient and inpatient anticoagulation therapy and the risk for hospital admission and death among COVID-19 patients.

BackgroundCoronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state. Limited data exist informing the relationship between anticoagulation therapy and risk for COVID-19 related hospitalization and mortality.MethodsWe evaluated all patients over the age of 18 diagnosed with COVID-19 in a prospective cohort study from March 4th to August 27th, 2020 among 12 hospitals and 60 clinics of M Health Fairview system (USA). We investigated the relationship between (1) 90-day anticoagulation therapy among outpatients before COVID-19 diagnosis and the risk for hospitalization and mortality and (2) Inpatient anticoagulation therapy and mortality risk.FindingsOf 6195 patients, 598 were immediately hospitalized and 5597 were treated as outpatients. The overall case-fatality rate was 2•8% (n = 175 deaths). Among the patients who were hospitalized, the inpatient mortality was 13%. Among the 5597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation and 331 were eventually hospitalized (5.9%). In a multivariable analysis, outpatient anticoagulation use was associated with a 43% reduction in risk for hospital admission, HR (95% CI = 0.57, 0.38–0.86), p = 0.007, but was not associated with mortality, HR (95% CI=0.88, 0.50 - 1.52), p = 0.64. Inpatients who were not on anticoagulation (before or after hospitalization) had an increased risk for mortality, HR (95% CI = 2.26, 1.17–4.37), p = 0.015.InterpretationOutpatients with COVID-19 who were on outpatient anticoagulation at the time of diagnosis experienced a 43% reduced risk of hospitalization. Failure to initiate anticoagulation upon hospitalization or maintaining outpatient anticoagulation in hospitalized COVID-19 patients was associated with increased mortality risk.FundingNo funding was obtained for this study.

Evaluation of a Risk-Stratified, Heparin-Based, Obstetric Thromboprophylaxis Protocol.

To evaluate outcomes before and after implementation of a risk-stratified heparin-based obstetric thromboprophylaxis protocol. We performed a retrospective cohort study of all patients who delivered at our tertiary care center from 2013 to 2018. Deliveries were categorized as preprotocol (2013-2015; no standardized heparin-based thromboprophylaxis) and postprotocol (2016-2018). Patients receiving outpatient anticoagulation for active venous thromboembolism (VTE) or high VTE risk were excluded. Coprimary effectiveness and safety outcomes were postpartum VTEs and wound hematomas, respectively, newly diagnosed after delivery and up to 6 weeks postpartum. Secondary outcomes were other wound or bleeding complications, including unplanned surgical procedures (eg, hysterectomies, wound explorations) and blood transfusions. Outcomes were compared between groups, and adjusted odds ratios (aORs) and 95% CIs were calculated using the preprotocol group as reference. Of 24,229 deliveries, 11,799 (49%) occurred preprotocol. Although patients were more likely to receive heparin-based prophylaxis postprotocol (15.6% vs 1.2%, P<.001), there was no difference in VTE frequency between groups (0.1% vs 0.1%, odds ratio 1.0, 95% CI 0.5-2.1). However, patients postprotocol experienced significantly more wound hematomas (0.7% vs 0.4%, aOR 2.34, 95% CI 1.54-3.57), unplanned surgical procedures (aOR 1.29, 95% CI 1.06-1.57), and blood transfusions (aOR 1.34, 95% CI 1.16-1.55). Risk-stratified heparin-based thromboprophylaxis in a general obstetric population was associated with increased wound and bleeding complications without a complementary decrease in postpartum VTE. Guidelines recommending this strategy should be reconsidered.

Outpatient Chronic Anticoagulation Improves Outcomes in Patients With Coronavirus Disease 2019 and Cardiovascular Risk Factors

In 2020, coronavirus disease 2019 (COVID-19) was the leading cause of death for patients with cardiovascular risk factors. Recent studies have suggested that inpatient anticoagulation can reduce the relative risk of mortality for patients already hospitalized due to COVID-19. It remains unknown whether outpatient therapeutic anticoagulation can reduce the risk of hospitalization/intensive care unit (ICU) admission, multisystem organ failure (MSOF), and death for patients with cardiovascular disease after COVID-19 infection.

Utilization of anti-factor Xa levels to guide reversal of oral factor Xa inhibitors in the emergency department.

PurposeOral factor Xa inhibitors (FXaIs) are increasingly utilized for outpatient anticoagulation therapy; however, laboratory monitoring is not routinely used to assess the safety and efficacy of these agents. We aimed to evaluate the role of chromogenic anti–factor Xa (anti-Xa) assays in the emergency department (ED) in the setting of patients with an acute bleed or requiring emergent procedures.MethodsA retrospective review of anti-Xa levels obtained in the ED between June 1, 2019, and April 30, 2020, was completed. Data were collected to describe the clinical setting of anti-Xa level collection, oral FXaIs used before admission, administration of reversal agents, and patient disposition to further characterize the role of anti-Xa levels in the management of rivaroxaban and apixaban reversal.ResultsThirty anti-Xa levels were included in the final analysis. The median time from sample collection to anti-Xa assay result was 45.9 minutes (interquartile range, 35.3-54.7 minutes). Eleven patients (37%) received anticoagulation reversal after their anti-Xa levels were determined. Anticoagulation reversal agents included either activated prothrombin complex concentrates (aPCCs) or prothrombin complex concentrates (PCCs). Anti-Xa levels were collected in 2 patients who had received PCCs before arrival at our ED. Of the patients with anti-Xa levels below 30 ng/mL, none received aPCCs or PCCs after their anti-Xa levels were determined. Anti-Xa assays were used to rule out the presence of FXaIs in 3 patients.ConclusionThis study illustrates the novel role of anti-Xa levels in managing patients with an emergent need for reversal in the ED. The assay may be used to rule out the presence of oral FXaIs and avoid unnecessary administrations of anticoagulation reversal agents.

The Impact of Adding Aspirin to Warfarin without an Apparent Indication: An Exploration of Patients Anticoagulated for Atrial Fibrillation or Venous Thromboembolic Disease

▪Introduction: Warfarin and aspirin (ASA) are widely used to prevent or treat thromboembolic and atherosclerotic diseases. The most common indications for warfarin use are stroke prevention in atrial fibrillation (AF) and for the treatment of venous thromboembolic disease (VTE). When patients are started on warfarin, many are already taking ASA or they are subsequently placed on ASA due to other co-morbidities. There are limited indications for the combination of warfarin plus ASA, including mechanical heart valves, after percutaneous coronary intervention (PCI), or after acute coronary syndromes. Evidence suggests combination warfarin-ASA may offer no benefit, but place patients at increased bleeding risk outside of these indications.We sought to assess the patient characteristics and outcomes of patients on warfarin for AF or VTE, comparing those who were on concurrent ASA without a strong indication (myocardial infarction [MI] within 6 months, mechanical heart valve or PCI) to those not on ASA. We hypothesized that combination therapy (warfarin-ASA) would result in increased bleeding rates with similar rates of MI, recurrent VTE, stroke, or death.Methods: We conducted a retrospective cohort study of adult patients, initiated on warfarin for AF or VTE between January 2009 and June 2017. Patients were recruited through the Michigan Anticoagulation Quality Improvement Initiative, a collaborative of six outpatient anticoagulation clinics throughout the state of Michigan. Patients with less than three months of follow-up, a MI within six months, and/or history of valve replacement were excluded. Patients were analyzed based on their aspirin use at the time of study enrollment. A HAS-BLED score, modified to exclude aspirin use, and a Charlson Co-morbidity Index was calculated for each patient at enrollment.Analyses were performed using Student's t-tests, Wilcoxon Rank-sum tests, chi-square tests and Fisher's exact tests when appropriate. Survival and Poisson regression analyses were used to evaluate the effect of ASA use on various outcomes.Results: A total of 6,572 patients met the inclusion criteria, with a mean duration of follow-up of 21.2 months; 38% were on warfarin-ASA compared to 62% on warfarin monotherapy. Patients on warfarin-ASA were older (mean 70.2±12.7 vs. 63.7±16.5, p<0.001), more often male (56.7% vs. 47.3%, p<0.001), and were more likely anticoagulated for AF (66.3% vs. 42.3%, p<0.001). Warfarin-ASA patients were more likely to have cardiovascular risk factors (diabetes mellitus, tobacco use, or hypertension), a history of stroke, heart failure, or a history of coronary artery disease (CAD). Patients on warfarin-ASA had a higher HAS-BLED score (mean 2.4±1.2 vs. 1.8±1.2, p<0.001), and Charlson Co-morbidity Index (mean 4.8±2.0 vs. 3.6±2.1, p<0.001).Patients treated with warfarin-ASA vs. warfarin alone experienced less DVTs (0.7/100 patient years [pt-yr] vs. 1.3/100-pt-yr, p=0.002) and PE (0.1/100-pt-yr vs. 0.4/100-pt-yr, p=0.002), but had a higher rate of ischemic/embolic strokes (0.7/100-pt-yr vs. 0.4/100-pt-yr, p=0.02). Emergency department visits and hospitalizations for thromboembolic events were similar. Patients treated with warfarin-ASA vs. warfarin alone had a higher 1-year probability of having a major bleeding event (6.1% vs. 3.2%, p<0.001) or non-major bleeding event (22.9% vs. 18.7%, p=0.004). Warfarin-ASA treated patients had a higher rate of hospitalizations for bleeding (8.4/100-pt-yr vs. 5.7/100-pt-yr, p<0.001), blood transfusions (5.2/100-pt-yr vs. 4.1/100-pt-yr, p=0.009) and all-cause mortality relative to warfarin alone (4.1/100-pt-yr vs. 3.1/100-pt-yr, p=0.005). Kaplan-Meier curves for any clotting event, all bleeding events, major bleeding events, and death are shown (figure 1). A sensitivity analysis was performed that further excluded any history of MI, CAD, PCI, peripheral arterial disease, or coronary artery bypass grafting, and showed similar results.Conclusion: Over one-third of patients in an unselected practice-based setting are treated with warfarin-ASA for AF and/or VTE without a clear indication. Compared to warfarin monotherapy, this was associated with minimally increased protection against VTE but with a significant increase in bleeding and perhaps mortality. Further research is needed to better stratify who should receive aspirin while on warfarin. [Display omitted] DisclosuresSood:Bayer: Research Funding. Kline-Rogers:Janssen: Consultancy; ACP: Consultancy; AC Forum: Membership on an entity's Board of Directors or advisory committees. Almany:Trice Orthopedics: Consultancy; Micardia: Consultancy; Ablative Solutions: Equity Ownership; Kona: Consultancy; Biostar Ventures: Equity Ownership; Boston Scientific Watchman: Research Funding; Abbott Absorb Trial: Research Funding. Kaatz:Daiichi Sankyo: Consultancy, Honoraria; CSL Behring: Honoraria; Boehringer Ingelheim: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Portola: Consultancy. Froehlich:Merck: Consultancy; Fibromuscular Disease Society of America: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Boehringer Ingelheim: Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy; Novartis: Consultancy; Pfizer: Membership on an entity's Board of Directors or advisory committees. Barnes:Pfizer: Research Funding; Bristol Myers Squibb: Research Funding; Blue Cross/Blue Shield of Michigan: Research Funding; Aralez: Consultancy.

Characterizing safety and efficacy in ovarian cancer patients with thromboembolism treated with rivaroxaban.

e18720 Background: There is a paucity of real-world data regarding rates of recurrent venous thromboembolism (VTE), major bleeding and all-cause mortality among ovarian cancer patients with thrombosis treated with direct oral anticoagulants (DOACs) currently available. We sought to evaluate the effectiveness and safety of rivaroxaban versus low molecular-weight heparin (LMWH) for cancer-associated thrombosis (CAT) treatment in patients with ovarian cancer. Methods: We utilized US Surveillance, Epidemiology and End Results-Medicare–linked data from 2013-2016 to identify adults with active ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Rivaroxaban and LMWH cohorts were balanced using propensity score overlap weighting . Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately and mortality at six-months using an intention-to-treat approach. On-treatment analysis after 12-months was also performed. Hazard ratios (HRs) with 95% confidence intervals using overlap weighted cox regression were reported. Results: We included 33 rivaroxaban and 92 LMWH-managed CAT patients. In each cohort, mean age was 73, 79.5% of patients were white, 46.9% had a history of ≥ stage 3 chronic kidney disease (CKD), two-thirds had metastatic disease at the time of VTE, and 32.6% had a prior VTE. Patients were diagnosed with ovarian cancer an average of 1.40 years prior to the index VTE event and 45.8% had a pulmonary embolism (with or without DVT) as the index event. Our analysis did not detect a significant difference in outcomes with rivaroxaban versus LMWH at six-months (Table). On-treatment analysis at 12-months showed similar results. Conclusions: Rivaroxaban may be a reasonable alternative to LMWH for CAT patients with ovarian cancer. Large observational studies are needed to confirm these results.[Table: see text]

Do differences in baseline clinical severity of ovarian cancer patients with thrombosis predict treatment with rivaroxaban versus low molecular-weight heparin?

e18748 Background: Prescribers use direct oral anticoagulants and low molecular-weight heparin (LMWH) for the acute treatment and secondary prevention of cancer-associated thrombosis (CAT). We sought to identify predictors impacting the use rivaroxaban versus LMWH for CAT in patients with ovarian cancer. Methods: Using US Surveillance, Epidemiology and End Result-Medicare linked data from 2013-2016, we evaluated adults with ovarian cancer, undergoing hospitalization/emergency department admission for CAT and prescribed rivaroxaban or LMWH for outpatient anticoagulation. Univariate analysis was performed to examine the association between covariates and clinicians’ choice to use rivaroxaban or LMWH. Variables with a p-value &lt; 0.20 upon univariate analysis were deemed significant and subsequently included into a stepwise, backwards multivariable logistic regression model to obtain adjusted odd ratios (ORs) of treatment assignment. Results: Of the 125 ovarian cancer patients included in our analysis, 26% received rivaroxaban and 74% LMWH. All patients had stage 3 or 4 ovarian cancer, 36% were ≥75 years-of-age, 78% were white, and 18% were below the poverty line (p ≥ 0.25). Upon univariate analysis, rural community, time between cancer diagnosis and VTE ≥ 1 year, index VTE without evidence of pulmonary embolism, and CKD ≥ stage 3 were found to be significant predictors of rivaroxaban use when compared to LMWH (p ≤ 0.14 for all). Upon multivariable regression, CKD ≥ stage 3 (OR = 3.13) was shown to be independently associated with rivaroxaban versus LMWH use (p≤0.01). Conclusions: In routine practice, patients were more likely to receive rivaroxaban if they had CKD and lived in a rural area. These differences in prescribing practices may be due to less availability of LMWH in rural areas and less tolerance of injections in CKD patients. Univariate analysis also suggest that low VTE burden (i.e., DVT only) and VTE event ≥ 1 year after cancer diagnosis were also associated with rivaroxaban use over LMWH, which may be due to LMWH therapy as the long-established standard of care for patients with cancer. Large observational studies are needed to confirm these results. [Table: see text]

Enoxaparin Use and Adverse Events in Outpatients With a Continuous Flow Left Ventricular Assist Device at a Single Institution

Background: Patients with left ventricular assist devices (LVADs) are anticoagulated with warfarin and may receive enoxaparin bridging for a subtherapeutic international normalized ratio (INR). There is no guideline regarding enoxaparin bridging in LVAD patients and a dosing strategy to ensure efficacy and safety is uncertain. Objective: The objective was to characterize the use of enoxaparin bridging for subtherapeutic INRs and its impact on thrombotic or major bleeding events (MBE) in patients with an LVAD. Methods: A retrospective review from 6/1/17 to 6/30/18 was performed. Patients with an LVAD were excluded if they had less than 60 days of outpatient anticoagulation or age <18 years old. Patients were divided into 2 cohorts based on enoxaparin exposure. MBE and thrombotic events were classified as related to enoxaparin if events occurred while receiving enoxaparin and up to 7 days or 30 days, respectively, after discontinuation. Results: Seventy-one LVAD patients met inclusion criteria and 50 patients received enoxaparin bridging. Therapeutic-dose enoxaparin was initiated at a mean INR of 1.8 for a mean duration of 2.8 days. In the enoxaparin exposure group, one MBE occurred 6 days after enoxaparin discontinuation, coinciding with an INR increase from 1.8 to 4.7. One thrombotic event occurred 2 days after enoxaparin discontinuation at an INR of 5.0. Conclusion: This institution’s bridging strategy of therapeutic-dose enoxaparin with a short duration has a low rate of bleeding and thrombotic events. Additional prospective studies of anticoagulation bridging based on characteristics such as type of LVAD device are warranted.

Abstract P112: Markers of Coagulation and Hemostatic Activation Identify Covid-19 Patients at High Risk for Thrombotic Events

Introduction: COVID-19 has been associated with venous and arterial thrombotic complications. The objective of our study was to determine whether markers of coagulation and hemostatic activation (MOCHA) on admission could identify COVID-19 patients at risk for thrombotic events. Methods: COVID-19 patients admitted to a tertiary academic healthcare system from April 3, 2020 to July 31, 2020 underwent admission testing of MOCHA profile parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, and fibrin monomer). For this analysis we excluded patients on outpatient anticoagulation therapy preceding admission. Prespecified endpoints monitored during hospitalization included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke and access line thrombosis. Results: During the study period, 276 patients were included in the analysis cohort (mean age 59 ± 6.3 years, 47% female, 83% non-white race). Arterial and venous thrombotic events occurred in 43 (16%) patients (see Table). Each coagulation marker was independently associated with the composite endpoint (p&lt;0.05). Admission MOCHA with ≥ 2 abnormalities was associated with the composite endpoint (OR 3.1, 95% CI 1.2-8.3), ICU admission (OR 3.2, 95% CI 1.8-5.5) and intubation (OR 2.8, 95% CI 1.5-5.5). Admission MOCHA with &lt; 2 abnormalities (26% of the cohort) had sensitivity of 88% and a negative predictive value of 93% for an in-hospital endpoint. Conclusion: Admission MOCHA with ≥ 2 abnormalities identified COVID-19 patients at risk for a thrombotic event, ICU admission and intubation while &lt; 2 abnormalities identified a subgroup of patients who were at low risk for thrombotic events. Our results suggest that an admission MOCHA profile can be useful to risk stratify COVID-19 patients. Further studies are needed to determine whether an admission MOCHA profile can guide anticoagulation therapy and improve overall clinical outcomes.

Knowledge, attitude, and practice regarding atrial fibrillation among primary care physicians: the potential role of postgraduate training.

Atrial fibrillation (AF) is known to lead to stroke and thromboembolism, causing a five-fold increase in the risk of stroke and almost doubling the mortality rate. Optimal anticoagulant therapy is effective in reducing AF-related death. However, prescription of anticoagulants in AF in East Asian countries has been low, ranging from 0.5% to 28%. This study aimed to determine whether vocational training in family medicine improves primary care physicians' knowledge, attitude, and practice in the management of AF. This investigation was a cross-sectional study carried out during centralized workshops for two groups of trainees using a validated questionnaire: (i) junior trainees were newly enrolled postgraduate trainees in the Graduate Certificate in Family Medicine (GCFM) program, and (ii) senior trainees were postgraduate trainees in Advance Training in Family Medicine (ATFM) programs of the Academy of Family Physicians of Malaysia (AFPM). A total of 223 trainees (127 junior and 96 senior) participated in this study. Only 55.2% of the trainees passed the knowledge test; senior trainees were more likely to pass the knowledge test compared to junior trainees (69.8% vs. 44.1%, p < 0.001). Female trainees were significantly more likely to pass the knowledge test than male trainees. While the attitude of senior and junior trainees was similar, more of the latter group worked in public clinic that provide better support where there is better support for outpatient anticoagulation treatment (e.g., same-day INR test, direct access echocardiogram, and warfarin in in-house pharmacy). Vocational training in family medicine appears to improve primary care physicians' knowledge regarding the management of AF. Better knowledge will help vocationally trained primary care physicians to provide anticoagulation treatment for AF within primary care clinics. More optimal AF management within primary care can take place if the identified barriers are addressed and a shared care plan can be implemented.

794 Venous thromboembolism and adverse outcomes in highest-VTE risk gravidas compared to those at lower risk

At our institution, we found that a risk-based protocol for inpatient heparin-based venous thromboembolism (VTE) prophylaxis (ppx) in obstetric patients with low- and medium-VTE risk resulted in 180 hematomas for every 1 VTE prevented. Herein, we compare rates of VTE and bleeding outcomes in women at highest risk for VTE (i.e. high-risk thrombophilia, active VTE who require anticoagulation ppx or therapy (tx) throughout pregnancy) compared to lower-risk gravidas. Retrospective cohort study of all deliveries >20 weeks at a single center (2013-2018). Women were categorized as high-risk (HR; received outpatient heparin-based ppx/tx, see Table 1 footnote for all indications) or lower-risk (LR; no outpatient anticoagulation).The primary efficacy outcome was any newly diagnosed postpartum VTE; the primary safety outcome was wound/perineal hematoma (all outcomes in Table 2). Outcomes were compared between HR and LR cohorts; adjusted odds ratios (95% CIs) were calculated with the LR group as reference. Of 24,303 total deliveries, 398 (2%) were HR, and 23,905 (98%) were LR. Of LR women, 8.6% received anticoagulation ppx in accordance with our risk-based inpatient VTE ppx protocol. HR and LR women were significantly different at baseline (Table 1). Despite outpatient antepartum anticoagulation, HR women had a 10-fold increased risk of VTE (aOR 10.6 [4.4-25.1] compared to LR women. HR women also had significantly more wound/perineal hematomas (aOR 2.5 [1.1-5.8]), overall wound/postoperative complications, blood transfusions, ICU admissions, maternal deaths and longer maternal lengths of stay (Table 2). Women at highest risk for obstetric VTE had significantly more VTEs and postpartum wound/bleeding complications when compared to LR women. Given the 10-fold increased risk of VTE in these high-risk women, even with outpatient anticoagulation, with only a moderate increase in adverse bleeding outcomes, this favorable risk/benefit profile supports current anticoagulation recommendations in HR women, while it questions routine obstetric VTE ppx in LR women (NNT 60,000; NNH 333).View Large Image Figure ViewerDownload Hi-res image Download (PPT)

A case series of the rifampin-warfarin drug interaction: focus on practical warfarin management.

To provide practical guidance by providing weekly descriptions of warfarin requirements for the onset and offset of the rifampin-warfarin interaction. A retrospective chart review within an outpatient Anticoagulation Clinic (AC). Patients were eligible for the onset phase provided they had known ambulatory-based warfarin steady-state requirements prior to rifampin initiation. For the offset phase, warfarin must be managed by the AC following rifampin discontinuation. Each phase was described separately with warfarin proportionate dose changes (median, IQR) for weeks 1, 2, and 4 as well as the change required to reach warfarin steady state. Ten patients with 11 courses of warfarin-rifampin were included. For onset, clinicians should anticipate proportionate warfarin dose increases of 30-80% from week 1 to week 2 and a further 20-100% from week 2 to 4, with an overall warfarin dose increase of 165% (IQR 99, 227) to reach steady state at 30days. For offset, clinicians should anticipate proportionate warfarin dose decreases of 15-25% for both week 1 and 2, and a further 20% for both week 3 and 4, resulting in an overall warfarin decrease of 67% (IQR - 70, - 58) to reach steady state at 4weeks for most patients. Close monitoring with at least twice weekly INRs for weeks 1 to 2 of both phases is needed to respond to substantially changing warfarin dose requirements. While inter- and intra-patient variability for proportionate warfarin dose changes for both the onset and offset of this drug interaction exists, our data provides general guidance.

Open-Heart Surgery in Low-Income Settings: The Experience of &lt;i&gt;Salam&lt;/i&gt; Centre for Cardiac Surgery in Sudan (2007–2019)

Background: Despite the need for cardiac surgery in Sub-Saharan Africa, access is still very limited. Active since 2007, the Salam Centre for Cardiac Surgery, run by EMERGENCY NGO and co-financed by the Sudanese government, offers heart surgery free of charge. Methods: Retrospective cohort study of 8369 consecutive patients undergoing open-heart surgery between 2007 and 2019, from Sudan (81%) and from neighbouring countries (19%). Findings: Rheumatic heart disease (RHD) was prevalent in 80% of adults (median age 28, Q1-Q3 20-37); with 43% isolated mitral, 11% aortic and 46% multiple valve procedures. Out of the 1396 (17%) patients with congenital heart disease (CHD), 74% were children (< 15 years). Continuity over the years and the low hospital/ 30 days mortality (2·9% RHD; 3·4% CHD) reflect the quality of in-hospital care. Outpatient and oral anticoagulation clinics ensured care after discharge, leading to a 5-years loss-to-follow-up for RHD patients of 18% and a 5-years overall survival of 89.6% (95% CI: 88.9-90.3), with values over 90% for MV and AV surgeries . The programme has also provided training for more than 400 local healthcare workers (2013–2019). Interpretation: The overall favorable results strongly support the original hypothesis that quality, gratuity, and long-term commitment represent the key elements in the collaboration between a humanitarian independent NGO and institutional actors, paving the way for wider, sustainable developments. Funding: The SALAM Centre is funded by EMERGENCY-NGO and by the Sudanese Government. The average Government Contribution in 2007-2019 amounts to 32% of the project’s overall costs, reaching 50% in 2014-2017. Declaration of Interest: We declare no competing interests. Ethical Approval: The institutional ethics board of the University of Milan have approved this study and, due to the nature of retrospective chart reviews, waived the need for informed consent from individual patients.

Successful outcome with outpatient acenocoumarol therapy for echocardiographically visible pulmonary thrombus

Visualisation of thrombus in the main pulmonary artery through two-dimensional transthoracic echocardiography (TTE) without cardiovascular instability is rare. We report a unique case of echocardiographically diagnosed acute pulmonary embolism (PE) in an ambulatory patient with concomitant cor pulmonale secondary to idiopathic interstitial lung disease. The mobile thrombus was first visualised at the junction of bifurcation of the pulmonary trunk with left pulmonary artery through routine two-dimensional TTE. Two days later, the contrast-enhanced computerised tomographic scan of the chest showed the thrombus to be in the distal portion of the right pulmonary artery. Complete resolution of pulmonary thrombus was achieved with a 3-month course of outpatient oral anticoagulation treatment with acenocoumarol without recurrence of PE during the 1-year follow-up.

Outpatient and Inpatient Anticoagulation Therapy and the Risk for Hospital Admission and Death Among COVID-19 Patients

Background: Coronavirus disease 2019 (COVID-19) is associated with a hypercoagulable state that increases the risk for thrombosis, hospitalization, and mortality. Limited data exist informing the relationship between outpatient anticoagulation therapy 90 days prior to diagnosis and risk for COVID-19 related hospitalization and mortality.Methods: This is a prospective cohort study from March 4th and August 27th, 2020 among 12 hospitals and 60 clinics. We evaluated all patients over the age of 18 diagnosed with COVID-19 for a total of 6,195 consecutive patients.Objectives: We investigated the relationship between 90-day anticoagulation therapy among outpatients prior to COVID-19 diagnosis (OPAC) therapy and the risk for 45 days hospitalization, and mortality as well as the relationship between inpatient prophylactic, escalated prophylactic, or therapeutic anticoagulation (IPAC) therapy and 45 days mortality risk.Results: 598 were immediately hospitalized, and 5,597 were initially treated as outpatients. The case fatality rate was 2.8% (n=175 deaths) and 13% for the overall 45 days mortality and inpatient mortality respectively. Among 5,597 COVID-19 patients initially treated as outpatients, 160 (2.9%) were on anticoagulation, and 331 were hospitalized (5.9%). In a multivariable analysis, OPAC use was associated with a 43% reduction in risk for hospital admission, HR (95%CI)=0.57 (0.38, 0.86), p=0.007, but was not associated with mortality, HR (95%CI)=0.88 (0.50, 1.52), p=0.64. In comparison to inpatients who continued anticoagulation therapy upon admission, inpatients who never initiated anticoagulation (before or after hospitalization) realized increased mortality risk, HR (95%CI)=2.26 (1.17, 4.37), p=0.015, while inpatients who initiated anticoagulation upon admission realized no increased risk for mortality HR(95%CI)=1.27(0.75,2.14), p=0.38.Conclusion: Outpatients with COVID-19 using anticoagulation experienced a 43% reduced risk of hospitalization, and initiation of anticoagulation among inpatients was not associated with increased mortality risk.Funding Statement: No specific grant funding was obtained for this study.Declaration of Interests: Dr. Tignanelli is a principal investigator on randomized trials for Covid-19, but not related to anticoagulation. Dr. Haslbauer and Dr. Tzankov received funding support from the Botnar Research Centre for Child Health for all their COVID-19 related research. The remaining authors have nothing to disclose. Ethics Approval Statement: This study was approved by the University of Minnesota’s institutional review board (IRB).

Drive-thru anticoagulation clinic: Can we supersize your care today?

Warfarin therapy requires maintenance of a therapeutic international normalized ratio (INR) and thus requires routine monitoring to ensure benefits of anticoagulation, while avoiding complications. As the pharmacist’s role evolves from traditional medication dispensing towards direct patient care, many anticoagulation management services are pharmacist-managed. Due to the coronavirus disease 2019 (COVID-19) pandemic, healthcare providers were faced with re-evaluating anticoagulation management practices to minimize person-to-person exposure risk. Although being anticoagulated is not considered high risk for illness from the coronavirus, these patients are often of advanced age and frequently have multiple comorbidities, putting them at increased risk. Consequently, two hospital-based, pharmacist-managed outpatient anticoagulation management services developed drive-thru curbside clinics to continue providing care to warfarin patients. The services utilized universal COVID-19 precautions to conduct curbside appointments where pharmacists determined patient’s warfarin therapy plan, scheduled timely follow-up, and provided dosing instructions. With the unexpected coronavirus outbreak, this immediate change to traditional anticoagulation management was essential for safe and effective anticoagulation therapy. Implementing a curbside clinic allowed for safe distancing while managing warfarin appropriately.

Determinants of Anticoagulation Control in Patients Receiving Warfarin Therapy

Background: Warfarin, nowadays is considered one of the most prescribed anticoagulant medications. In England for example, there is at least 1% of the whole population being prescribed warfarin. Despite the emergence of new agents of anticoagulants like NOACS, warfarin still prevail in most prescriptions knowing that it can’t be substituted in certain indications. Objectives: To assess different factors associated with International Normalized Ratio (INR) control in patients who are on warfarin therapy for different indications. Methods: A retrospective cohort study conducted in National Heart Institute Outpatient Anticoagulation Clinic over six-month period. It included 250 patients on warfarin therapy for different indications. Results: After calculating Time in Therapeutic Range (TTR) of each patient the level of anticoagulation control was determined using the following cut off values: a) Good control: TTR>70%, b) Intermediate control: TTR 50 -70 %, c) Poor control: TTR <50%. Majority of patients in our study 62% had poor control with TTR less than 50%. Conclusion: Majority of patients have poor anticoagulation control by means of TTR. Male gender, higher education and employment status are associated with higher mean TTR and better anticoagulation control. Male gender and employment were significant predictors for good INR control.

Determinants of Anticoagulation Control in Patients Receiving Warfarin Therapy

Background: Warfarin, nowadays is considered one of the most prescribed anticoagulant medications. In England for example, there is at least 1% of the whole population being prescribed warfarin. Despite the emergence of new agents of anticoagulants like NOACS, warfarin still prevail in most prescriptions knowing that it can’t be substituted in certain indications. Objectives: To assess different factors associated with International Normalized Ratio (INR) control in patients who are on warfarin therapy for different indications. Methods: A retrospective cohort study conducted in National Heart Institute Outpatient Anticoagulation Clinic over six-month period. It included 250 patients on warfarin therapy for different indications. Results: After calculating Time in Therapeutic Range (TTR) of each patient the level of anticoagulation control was determined using the following cut off values: a) Good control: TTR>70%, b) Intermediate control: TTR 50 -70 %, c) Poor control: TTR <50%. Majority of patients in our study 62% had poor control with TTR less than 50%. Conclusion: Majority of patients have poor anticoagulation control by means of TTR. Male gender, higher education and employment status are associated with higher mean TTR and better anticoagulation control. Male gender and employment were significant predictors for good INR control.

Effectiveness and safety of rivaroxaban compared with low-molecular-weight heparin in cancer-associated thromboembolism

AbstractGuidelines provide differing recommendations regarding direct-acting oral anticoagulants vs low-molecular-weight heparin (LMWH) for treatment of cancer-associated thrombosis (CAT). This study was undertaken to evaluate the effectiveness and safety of rivaroxaban vs LMWH for treatment of CAT. Using US Surveillance, Epidemiology and End Results-Medicare–linked data from 2013 through 2016, we evaluated adults with active breast, lung, ovarian, or pancreatic cancer, who were admitted to the hospital or treated in the emergency department for CAT and were prescribed rivaroxaban or LMWH for outpatient anticoagulation. Patients with luminal gastrointestinal or genitourinary cancers were excluded. Rivaroxaban and LMWH users were 1:1 propensity score matched. Outcomes included the composite of recurrent thrombosis or major bleeding, each outcome separately, and mortality at 6 months, using an intent-to-treat approach. On-treatment analysis after 12 months was also performed. Proportional hazards models for the subdistribution of competing risk were used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs). We included 529 rivaroxaban- and 529 LMWH-treated patients with CAT. Rivaroxaban was not associated with differences in risk of the composite outcome (HR, 0.71; 95% CI, 0.41-1.22), major bleeding (HR, 1.01; 95% CI, 0.50-2.01), or mortality (HR, 0.87; 95% CI, 0.70-1.07) vs LMWH, but it reduced recurrent thrombosis (HR, 0.37; 95% CI, 0.15-0.95). On-treatment analysis at 12 months showed similar results. Rivaroxaban may be a reasonable alternative to LMWH for patients with CAT without gastrointestinal or genitourinary cancer.

Anticoagulant efficacy of different pharmacological presentations of vitamin K antagonists

Vitamin K antagonist medications (VKA) are essential for the prevention of thromboembolic events, but their effectiveness is influenced by multiple factors, such as the type of medication chosen. To evaluate the efficacy in anticoagulant control of the bioequivalent and non-bioequivalent drugs of acenocoumarol compared to the reference drug. To evaluate the efficacy of warfarin bioequivalents available in Chile. To contrast the overall anticoagulant control efficacy between acenocoumarol and warfarin. The results of 69333 outpatient oral anticoagulation controls were analyzed. Patient were separated in groups according to the drug that they used. Subsequently, the proportions of controls outside the range for each of acenocoumarol and warfarin bioequivalent drugs were compared. Acenocoumarol non-bioequivalent drugs were also compared with the reference drug. Acenocoumarol was compared with warfarin. Acenocoumarol bioequivalent drugs and the reference drug had a similar proportion of controls outside the range (Odds ratios (OR) 0.812; 0.969; 0.974 and 0.963). Non-bioequivalent drugs had a higher proportion than the reference drug (OR 1.561 and 2.037). Both warfarin brands have a similar proportion of controls outside of the range (OR 1.050). Acenocoumarol compared to warfarin had a significant higher proportion of controls outside the range (OR 1.191). The pharmacological presentation of vitamin K antagonists could influence anticoagulant control. Therefore, it is not prudent to switch these presentations frequently.