Essentials
It is not clear if patients are less adherent to low molecular weight heparin (LMWH) compared to direct oral anticoagulants (DOACs) for cancer‐associated thrombosis (CAT).
We evaluated ...medication adherence among two propensity‐matched groups of patients with CAT by comparing the proportion of days covered (PDC).
Median treatment persistence on DOACs was more than 80 days longer than LMWH.
Medication adherence was high (~95%) and was similar with LMWH compared to DOACs.
Background
Low molecular weight heparin (LMWH) and direct oral anticoagulants (DOACs) are used to treat cancer‐associated thrombosis (CAT). It is not clear if patients are less adherent to LMWH compared to DOACs.
Objectives
To compare medication persistence and adherence between LMWH and DOACs.
Patients/Methods
We analyzed Optum's de‐identified Clinformatics® Data Mart Database of privately insured adults with cancer diagnosed between January 2009 and October 2015 who were undergoing chemotherapy, immunotherapy, targeted or hormonal therapies; developed CAT; and were treated with an outpatient anticoagulant. The proportion of days covered (PDC) was calculated from the date of anticoagulant prescription until the anticoagulant was switched, stopped, or the study end. Medication adherence was defined as PDC ≥ 80%, ≥95%, and by comparing the mean PDC.
Results
Two propensity‐matched groups of 1128 patients were identified. Patient persistence was higher with DOACs compared to LMWH (median 116 days versus 34 days). With adherence defined as PDC ≥ 80%, we found no significant difference (95.6% versus 94.6% adherence with DOACs versus LMWH, P = .33). The mean difference of PDC between the two groups was also similar. With medication adherence defined as PDC ≥ 95%, adherence was evident in 73% of DOAC users and 81% of patients on LMWH (P < .001). Prescription copayments were higher on average for LMWH compared to DOACs (mean $153.61 versus 40.67; standard deviation $306.74 versus $33.11).
Conclusion
Patients remain on DOACs longer than LMWH, but medication adherence is similar with LMWH.
Symptoms suggestive of deep vein thrombosis (DVT) are extremely common in clinical practice, but unfortunately nonspecific. In both ambulatory and inpatient settings, clinicians are often tasked with ...evaluating these concerns. Here, we review the most recent advances in biomarkers and imaging to diagnose lower extremity DVT.
The modified Wells score remains the most supported clinical decision rule for risk stratifying patients. In uncomplicated patients, the D-dimer can be utilized with risk stratification to reasonably exclude lower extremity DVT in some patients. Although numerous biomarkers have been explored, soluble P-selectin has the most promise as a novel marker for DVT. Imaging will be required for many patients and ultrasound is the primary modality. Nuclear medicine techniques are under development, and computed tomography (CT) and magnetic resonance venography are reasonable alternatives in select patients.
D-dimer is the only clinically applied biomarker for DVT diagnosis, with soluble P-selectin a promising novel biomarker. Recent studies have identified several other potential biomarkers. Ultrasound remains the imaging modality of choice, but CT, MRI, or nuclear medicine tests can be considered in select scenarios.
It is unclear how many patients treated with a direct oral anticoagulant (DOAC) are using concomitant acetylsalicylic acid (ASA, or aspirin) and how this affects clinical outcomes.
To evaluate the ...frequency and outcomes of prescription of concomitant ASA and DOAC therapy for patients with atrial fibrillation (AF) or venous thromboembolic disease (VTE).
This registry-based cohort study took place at 4 anticoagulation clinics in Michigan from January 2015 to December 2019. Eligible participants were adults undergoing treatment with a DOAC for AF or VTE, without a recent myocardial infarction (MI) or history of heart valve replacement, with at least 3 months of follow-up.
Use of ASA concomitant with DOAC therapy.
Rates of bleeding (any, nonmajor, major), rates of thrombosis (stroke, VTE, MI), emergency department visits, hospitalizations, and death.
Of the study cohort of 3280 patients (1673 51.0% men; mean SD age 68.2 13.3 years), 1107 (33.8%) patients without a clear indication for ASA were being treated with DOACs and ASA. Two propensity score-matched cohorts, each with 1047 patients, were analyzed (DOAC plus ASA and DOAC only). Patients were followed up for a mean (SD) of 20.9 (19.0) months. Patients taking DOAC and ASA experienced more bleeding events compared with DOAC monotherapy (26.0 bleeds vs 31.6 bleeds per 100 patient years, P = .01). Specifically, patients undergoing combination therapy had significantly higher rates of nonmajor bleeding (26.1 bleeds vs 21.7 bleeds per 100 patient years, P = .02) compared with DOAC monotherapy. Major bleeding rates were similar between the 2 cohorts. Thrombotic event rates were also similar between the cohorts (2.5 events vs 2.3 events per 100 patient years for patients treated with DOAC and ASA compared with DOAC monotherapy, P = .80). Patients were more often hospitalized while undergoing combination therapy (9.1 vs 6.5 admissions per 100 patient years, P = .02).
Nearly one-third of patients with AF and/or VTE who were treated with a DOAC received ASA without a clear indication. Compared with DOAC monotherapy, concurrent DOAC and ASA use was associated with increased bleeding and hospitalizations but similar observed thrombosis rate. Future research should identify and deprescribe ASA for patients when the risk exceeds the anticipated benefit.
It is not clear how often patients receive aspirin (acetylsalicylic acid) while receiving oral anticoagulation with warfarin sodium without a clear therapeutic indication for aspirin, such as a ...mechanical heart valve replacement, recent percutaneous coronary intervention, or acute coronary syndrome. The clinical outcomes of such patients treated with warfarin and aspirin therapy compared with warfarin monotherapy are not well defined to date.
To evaluate the frequency and outcomes of adding aspirin to warfarin for patients without a clear therapeutic indication for combination therapy.
A registry-based cohort study of adults enrolled at 6 anticoagulation clinics in Michigan (January 1, 2010, to December 31, 2017) who were receiving warfarin therapy for atrial fibrillation or venous thromboembolism without documentation of a recent myocardial infarction or history of valve replacement.
Aspirin use without therapeutic indication.
Rates of any bleeding, major bleeding events, emergency department visits, hospitalizations, and thrombotic events at 1, 2, and 3 years.
Of the study cohort of 6539 patients (3326 men 50.9%; mean SD age, 66.1 15.5 years), 2453 patients (37.5%) without a clear therapeutic indication for aspirin were receiving combination warfarin and aspirin therapy. Data from 2 propensity score-matched cohorts of 1844 patients were analyzed (warfarin and aspirin vs warfarin only). At 1 year, patients receiving combination warfarin and aspirin compared with those receiving warfarin only had higher rates of overall bleeding (cumulative incidence, 26.0%; 95% CI, 23.8%-28.3% vs 20.3%; 95% CI, 18.3%-22.3%; P < .001), major bleeding (5.7%; 95% CI, 4.6%-7.1% vs 3.3%; 95% CI, 2.4%-4.3%; P < .001), emergency department visits for bleeding (13.3%; 95% CI, 11.6%-15.1% vs 9.8%; 95% CI, 8.4%-11.4%; P = .001), and hospitalizations for bleeding (8.1%; 6.8%-9.6% vs 5.2%; 4.1%-6.4%; P = .001). Rates of thrombosis were similar, with a 1-year cumulative incidence of 2.3% (95% CI, 1.6%-3.1%) for those receiving combination warfarin and aspirin therapy compared with 2.7% (95% CI, 2.0%-3.6%) for those receiving warfarin alone (P = .40). Similar findings persisted during 3 years of follow-up as well as in sensitivity analyses.
Compared with warfarin monotherapy, receipt of combination warfarin and aspirin therapy was associated with increased bleeding and similar observed rates of thrombosis. Further research is needed to better stratify which patients may benefit from aspirin while anticoagulated with warfarin for atrial fibrillation or venous thromboembolism; clinicians should be judicious in selecting patients for combination therapy.
The life expectancy of persons with hemophilia (PWH) has increased almost 10-fold over the past seven decades, largely due to access to safe factor replacement products. Concomitant with this ...success, however, comes the burden of aging. Older PWH are developing similar comorbidities as the general population, including increasing rates of hypertension, obesity, and diabetes, which predispose them to chronic diseases such as cardiovascular disease (CVD) and chronic kidney disease (CKD). How their coagulopathy affects the expression of these conditions remains unclear. In addition, the elderly hemophilia population must cope with chronic joint arthropathy, which provokes falls and fractures, and complications related to human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infections, which greatly impact the incidence of cancer and liver disease. With a dearth of evidence-based guidelines to direct therapy, a new challenge has arisen for hematologists to optimally manage these complex age-related issues. This review will focus on common complications affecting the older hemophilia population, including joint disease, CVD, malignancy, renal insufficiency, and liver disease.
With access to safe factor products, the life expectancy of persons with hemophilia (PWHs) has increased almost 10-fold over the past 7 decades. Unfortunately, hand in hand with this success comes ...the burden of aging. As PWHs age, they are subject to develop many of the same risk factors as the general population, including increasing rates of hypertension, obesity, and diabetes. Such comorbidities predispose them to chronic diseases, such as cardiovascular disease and chronic kidney disease, although how their coagulopathy affects the expression of these conditions remains unclear. The older hemophilia population faces additional challenges, such as chronic joint arthropathy, which provokes falls and fractures, and complications related to HIV and hepatitis C infections, which greatly affect the incidence of cancer and liver disease. In light of the paucity of evidence-based guidelines to direct therapy, a new challenge has arisen for hematologists to optimally manage these complex age-related issues. In general, elderly PWHs should be treated similarly to their peers without hemophilia, with the addition of factor replacement therapy as appropriate. Primary prevention of risk factors should be emphasized, and close coordination between specialties is essential. This review will focus on common complications affecting the older hemophilia population, including cardiovascular disease, malignancy, liver disease, renal insufficiency, and joint disease.
Venous thromboembolism is a leading cause of death in patients with cancer. Inferior vena cava filters are utilized to mitigate the risk of pulmonary embolism for patients who have contraindication ...to, or failure of, anticoagulation.
We reviewed an insurance claims database to identify adults receiving cancer-directed therapy and had a new diagnosis of venous thromboembolism. We then evaluated clinical and sociodemographic characteristics in patients with and without filter placement and retrieval.
There were 25,788 patients (mean SD age: 68.3 12.7 years) who met the study inclusion criteria, with 2111 individuals (8.2%) undergoing filter placement. Filter placement was associated with the type of thrombosis, malignancy, recent surgery, comorbidities, and income. A total of 137 patients (6.5%) newly started anticoagulation within 3 days of filter placement, and 612 (29%) patients received anticoagulation within 30 days after filter placement. Despite this, only 159 (7.5%) patients had their filters retrieved during the study period. Patients with income of $75-99K (odds ratio 2.13, P = .012) or above $100K (odds ratio 1.8, P = .038) were more likely to have filter retrieval compared with those with income <$50K. Filter retrieval was also more likely in younger patients and those with fewer comorbidities or without central nervous system or lung malignancies.
Inferior vena cava filter placement and retrieval are associated with several sociodemographic factors. Filter retrieval rates are low despite re-initiation of anticoagulation in many patients. Efforts are needed to address disparities in filter use and improve retrieval rates.
Many patients with antiphospholipid syndrome had decreased ectonucleotidase activity on neutrophils and platelets, which enabled extracellular nucleotides to trigger neutrophil-platelet aggregates. ...This phenotype was replicated by treating healthy neutrophils and platelets with patient-derived antiphospholipid antibodies or ectonucleotidase inhibitors.
Liver transplantation in patients with end-stage liver disease and coexisting hemophilia A has been described. Controversy exists over perioperative management of patients with factor VIII inhibitor ...predisposing patients to hemorrhage. We describe the case of a 58-year-old man with a history of hemophilia A and factor VIII inhibitor, eradicated with rituximab prior to living donor liver transplantation without recurrence of inhibitor. We also provide perioperative management recommendations from our successful multidisciplinary approach.
Abstract
Background
Patients with pancreatic cancer are at high risk of developing venous thromboembolism (VTE). It is unknown if aspirin reduces the risk of VTE in this setting.
Objectives
We ...sought to determine whether there is an association between aspirin use and VTE risk in patients with pancreatic cancer receiving chemotherapy with a central venous catheter (CVC).
Patients/Methods
We conducted a single-center, retrospective cohort study of adult patients diagnosed with pancreatic cancer and treated with chemotherapy using a CVC. Subjects were excluded if they were on anticoagulation at the time of CVC placement. The probability of VTE was analyzed using a time-to-event analysis framework for the development of VTE using the product-limit method of Kaplan and Meier (univariate) and adjusting for important confounding covariates using Cox proportional hazards regression (cause-specific hazard) and again using Fine and Gray regression (subdistributional hazard) with death prior to VTE considered a competing event.
Results
The final analysis included 314 cases (125 with any aspirin use and 189 without). Patients with any aspirin use had fewer VTE events (34.4%) compared with those without aspirin use (42.3%;
p
= 0.021) by log-rank test and after adjustment for multiple covariates using a Cox proportional hazards model (hazard ratio HR = 0.60; 95% confidence interval CI: 0.40–0.92;
p
= 0.019). Using Fine and Gray regression to account for death as a competing event, the effect of aspirin remained in the direction of benefit, but was not statistically significant (HR = 0.70; 95% CI: 0.47–1.05,
p
= 0.083). Higher body mass index, active smoking, and metastatic stage of cancer were associated with VTE events in the Cox proportional hazards model. Rates of major bleeding or clinically relevant minor bleeding were similar between treatment groups.
Conclusions
Aspirin may reduce the risk of VTE in patients with pancreatic cancer with a CVC. We did not observe a significant increase in the rates of major bleeding or clinically relevant nonmajor bleeding.
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