Evaluation of direct oral anticoagulants versus low molecular weight heparins for venous thromboembolism treatment in patients with gastrointestinal malignancies.

BACKGROUND: Direct oral anticoagulant (DOAC) use in cancer-associated venous thromboembolism (CA-VTE) has increased due to updates in recent guidelines and literature. However, select guidelines caution against DOAC use in patients with gastrointestinal (GI) malignancies due to reported increased bleeding events. The objective of this study was to compare the safety and effectiveness of DOACs versus low-molecular-weight heparins (LMWHs) for CA-VTE treatment in patients with GI malignancies. PATIENTS AND METHODS: This multicenter, retrospective cohort study included patients with primary GI malignancies who received therapeutic anticoagulation with a DOAC or LMWH for CA-VTE between January 1, 2018, and December 31, 2019. The primary outcome was the incidence rate of bleeding events (major, clinically relevant non-major, or minor bleeding events) within a 12-month period following the initiation of therapeutic anticoagulation. The secondary endpoint was the incidence rate of recurrent VTE events within a 12-month period following the start of therapeutic anticoagulation. RESULTS: After screening, 141 patients met inclusion criteria. The incidence rate of all bleeding events significantly differed between DOAC (4.98 events/100 person-months) and LWMH (10.2 events/100 person-months) recipients. The corresponding incidence rate ratio (IRR) with the DOAC group serving as the reference was 2.05 (p = 0.01), with the majority of bleeds in both groups presenting as minor bleeds. No difference was found between the incidence rate of recurrent VTE within a 12-month period of starting therapeutic anticoagulation between groups (IRR 3.08, p = 0.06). CONCLUSION: Our results suggest that DOACs do not pose an additional bleeding risk compared to LMWH in patients with certain GI malignancies. Careful selection of DOAC therapy with respect to bleeding risk is still warranted.

Optimizing quality of care in patients admitted with chronic obstructive pulmonary disease exacerbation.

Objectives: Adherence to Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) treatment is variable in the inpatient setting. This study evaluates appropriateness of therapy in patients admitted to an academic medical center for AECOPD. Methods: This was a single-center, retrospective, observational study. The primary endpoint was proportion of patients who received appropriate AECOPD treatment within 24 h. Secondary endpoints included mean length of stay (LOS) and time to administration (TTA) of pharmacotherapy, 30-day readmission rates, and proportions of various ancillary care received. Data were analyzed using descriptive and inferential statistics. Results: Of 533 screened admissions, 163 were included. Of those included, 55% (n = 90) received guideline-based therapy within 24 h of presentation. This group had significantly shorter mean LOS (3.48 ± 2.61 vs 4.53 ± 3.40 days, p = .026), fewer COPD-related readmissions (7 vs 14, p = .036), and numerically fewer all-cause readmissions (14 vs 19, p = .11). Mean LOS and TTA were 3.95 ± 3.02 days and 8.47 ± 12.77 h, respectively. Discussion: Timely and guideline-based delivery of medications was associated with shorter length of stay and fewer COPD-related readmissions. Establishing a standardized care plan through order set implementation may be one strategy to improve care and outcomes in AECOPD patients.

Pharmacy Resident Perspectives on the Layered Learning Practice Model.

Objective: To describe pharmacy resident perspectives on the layered learning practice model (LLPM) at large academic medical centers in the United States and identify the types of training residents receive to prepare for the LLPM. Methods: This was a cross-sectional, mixed methods study that surveyed pharmacy residents completing training at large, academic medical centers on their perspectives of the LLPM. Residents with at least 4 weeks of precepting experience were eligible to complete an online survey. Descriptive statistics were generated for demographic and Likert data while themes were identified from narrative free responses. Results: Twenty-seven resident responses from 10 institutions were included. Likert data showed generally positive perspectives toward overall experience with the LLPM and perceived LLPM impact on clinical knowledge and professional practice, with 100.0% of respondents agreeing they enjoyed precepting under the LLPM. However, 44.4% also agreed that precepting was stressful. LLPM impact on resident behavior received positive to neutral responses; 63.0% neither agreed nor disagreed that the LLPM changed their approach to patient care. Written comments revealed themes such as sources of stress within the LLPM, increased depth of learning, improved comprehensive patient care, and improved professional growth. The most common forms of LLPM training occurred through preceptor and student evaluations (73.1% and 61.5%, respectively) and orientation (50.0%). Conclusion: These findings identified a variety of resident perspectives on the LLPM ranging from positive to negative and revealed possible areas of improvement related to LLPM implementation. Residency programs may consider exploring stressors on the resident role in the LLPM to better structure resident precepting training and maximize their clinical learning experience.

Platelet response to direct thrombin inhibitor or fondaparinux treatment in patients with suspected heparin-induced thrombocytopenia.

Making a definitive diagnosis of heparin-induced thrombocytopenia (HIT) can be problematic. A prompt platelet rise following treatment has been proposed as a "post-test" criterion for diagnosis. However, the platelet response following discontinuation of heparin and initiation of a recommended alternative anticoagulant remains largely undefined and unstudied. This study aimed to characterize platelet response to initial treatment in patients with a low, intermediate, or high likelihood of having HIT. This was a multicenter retrospective cohort study. Patients were over 18 years in age, underwent serologic testing for HIT, and received alternative anticoagulation treatment for HIT. Classification of each patient's likelihood of having HIT was based on an empiric, pre-hoc combination of the 4T score and serology results. The primary outcome for this study was a platelet count response after initiation of direct thrombin inhibitor (DTI) or fondaparinux therapy within 48 h. 124 patients were analyzed. The sensitivity and specificity of having an immediate platelet rise of at least 10,000/µL by day 2 after starting treatment among high-likelihood for HIT patients were 0.71 (95% CI 0.55-0.84) and 0.64 (95% CI 0.5-0.76), respectively. The negative predictive value of no platelet rise was 75.5% (95% CI 0.61-0.86). A prompt platelet count rise may be appropriate to consider along with other known criteria for the clinical diagnosis of HIT. The rise should be immediate following discontinuation of heparin and initiation of recommended treatment, with an upward rise within 48 h.

Considerations for Systemic Anticoagulation in ESRD.

In the setting of end-stage kidney disease, the incidence and risk for thrombotic events are increased and use of anticoagulants is common. The incidence of bleeding, however, is also a frequent issue and creates additional challenges in the management of anticoagulation therapy. Patients with end-stage renal disease are typically excluded from large clinical trials exploring the use of anticoagulants, which limits our knowledge of optimal management approaches. Furthermore, varying degrees of renal failure in addition to conditions that alter the pharmacokinetics of various anticoagulants or pharmacodynamic response may warrant alternative approaches to dosing. This review will explore systemic chronic anticoagulation therapy in the setting of chronic kidney disease where hemodialysis is required. Agents discussed include vitamin K antagonists, low-molecular-weight heparins, fondaparinux, oral factor Xa antagonists, and direct thrombin inhibitors. Clinical challenges, approaches to dosing regimens, and tools for measuring responses and reversal will be explored.

Evaluation of standard versus reduced dose apixaban for the treatment of venous thromboembolism in patients with severe renal disease (ESRD-VTE).

BACKGROUND: There are no clear dosing recommendations when using apixaban for venous thromboembolism (VTE) treatment in patients with severe or end-stage renal disease; clinical trials excluded patients with a creatinine clearance (CrCl) <25 mL/min or on dialysis. This study compares bleeding rates in patients with severe or end-stage renal disease taking standard versus reduced dose apixaban for VTE treatment. MATERIALS AND METHODS: This was a multicenter, retrospective cohort study using electronic medical records between January 1, 2013, and August 31, 2021. This study included patients 18 years or older who had severe or end-stage renal disease when prescribed apixaban for VTE treatment. Severe or end-stage renal disease was defined as at least one of the following: CrCl <25 mL/min, SCr >2.5 mg/dL, CKD stage 4 or 5, or on dialysis. The primary endpoint was rate of clinically relevant bleeding within six months of starting apixaban. Secondary endpoints were VTE recurrence within six months of starting apixaban, time to clinically relevant bleed, and time to VTE recurrence. RESULTS: A total of 203 patients were included in the final analysis (n = 125 on 5 mg; n = 78 on 2.5 mg). Clinically relevant bleeding rate was significantly higher in the standard dose group (14.4 % vs 3.8 %, p = 0.02). Rates of VTE recurrence appear similar (6.4 % vs 7.7 %, p = 0.21). CONCLUSIONS: A reduced dose of apixaban may be considered when treating VTE in patients with severe or end-stage renal disease.

Direct oral anticoagulants or low-molecular-weight heparins for venous thromboembolism in patients with brain tumors.

INTRODUCTION: Patients with central nervous system malignancies have limited representation in studies evaluating DOACs for VTE treatment. This study evaluated the safety and efficacy of DOACs in comparison with LMWH for cancer-associated VTE in patients with primary brain tumors or secondary brain metastases. MATERIALS & METHODS: In this multicenter, retrospective cohort study, adult patients with a diagnosis of primary brain tumor or secondary brain metastases who received either a DOAC or LMWH for treatment of cancer-associated VTE were evaluated. The primary outcome was the cumulative incidence of any intracranial hemorrhage within a 6-month period following the initiation of anticoagulation. Secondary outcomes included the cumulative incidence of any bleeding event, and recurrent VTE events. RESULTS: Between January 1, 2012 and October 9, 2019, one-hundred eleven patients met inclusion criteria. The 6-month cumulative incidence of intracranial hemorrhage was 4.3% (95% CI, 0.74-13.2%) in the DOAC group, compared to 5.9% (95% CI, 1.5-14.9%) in the LMWH group (p = 0.61). The 6-month cumulative incidence of bleeding events was 14.3% (95% CI, 6.2-25.8%) in the DOAC group, compared to 27.8% (95% CI, 15.5-41.6%) in the LMWH group (p = 0.10). The 6-month cumulative incidence of recurrent VTE events was 5.6% in the DOAC group (95% CI, 1.5-14.2%), compared to 6.6% in the LMWH group (95% CI, 1.7-16.5%) (p = 0.96). No differences were found with respect to other secondary outcomes. CONCLUSION: There were no significant differences in bleeding or recurrent VTE events between DOACs and LMWH. These findings suggest DOACs may be safe and effective for VTE treatment in this patient population.

Utilization of venous thromboembolism prophylaxis in American hospitalized pregnant women undergoing cesarean section.

Background Pregnancy-related venous thromboembolism (VTE) is a leading preventable cause of maternal mortality in the United States; however, American guidelines for pharmacologic VTE prophylaxis remain less aggressive than other developed countries. The Safe Motherhood Initiative (SMI) combines aspects of American and international guidelines to increase utilization of prophylaxis and thereby decrease incidence of pregnancy-related VTE. Objectives To evaluate the prescribing and administration rates of pharmacologic VTE prophylaxis for women undergoing cesarean section (c-section) when retrospectively applying the SMI recommendations. Setting Large academic medical center in Sacramento, California, USA. Method This was a single-center retrospective cohort study of pregnant women undergoing c-section who would have met criteria for pharmacologic prophylaxis according to the SMI. Main outcome measures Prescribing and administration rates of mechanical and pharmacologic VTE prophylaxis. Secondary outcomes included incidence of thromboembolism within 6 weeks after c-section and thromboembolic associated mortality. Results A total of 616 charts were analyzed. When applying the SMI guidelines for VTE prophylaxis, the prescribing rates for mechanical and pharmacologic prophylaxis were 94.3% and 4.71% of patients, respectively, and 94.9% of ordered pharmacologic prophylaxis doses were administered. The incidence of 6-week post-partum VTE was 0.49%. There were no cases of VTE-associated mortality. Conclusion This study demonstrated that a large population of c-section patients fit the SMI criteria for pharmacologic VTE prophylaxis but did not receive it. We observed a 0.49% rate of VTE, which was slightly higher than the nationally reported average rate of 0.3%. With growing rates of pregnancy-associated VTE in the United States, perhaps a more aggressive guideline is warranted.

Subcutaneous enoxaparin for therapeutic anticoagulation in hemodialysis patients.

BACKGROUND: Information regarding dosing of low-molecular-weight heparins (LMWH) for therapeutic anticoagulation in hemodialysis (HD) patients is limited. The aim of this study was to retrospectively compare the safety and efficacy of enoxaparin versus unfractionated heparin (UFH) for therapeutic anticoagulation in HD patients. MATERIALS AND METHODS: This retrospective chart review evaluated HD patients treated with subcutaneous enoxaparin that were matched based on the indication for anticoagulation with patients treated with intravenous UFH to achieve therapeutic anticoagulation. Primary outcome measures included 30-day incidence of thromboembolic events and major bleeding. Secondary outcomes included rehospitalization within 30days, length of stay, and mortality. RESULTS: One hundred sixty-four patients were evaluated, 82 in each group. The average daily dose of enoxaparin used to target therapeutic levels was 0.7±0.2mg/kg/day (range=0.4-1). Comparing enoxaparin to UFH, there was no significant difference in major bleeding (6.1% vs 11%, p=0.4) or thromboembolism (0% vs 2.4%, p=0.5). Hospital length of stay was shorter in the enoxaparin group (20±53.8 vs 28.9±44.5days, p=0.02); there was no significant difference between groups in mortality or readmission. Adjusting for risk factors for bleeding there was a slight but statistically non-significant difference between enoxaparin versus UFH (OR=0.77, 95%CI: 0.2-3.5, p=0.73). CONCLUSIONS: These findings suggest that therapeutic dosing of enoxaparin, in doses that ranged from 0.4-1mg/kg/day, was as safe as intravenous UFH in providing therapeutic anticoagulation in stable patients requiring chronic hemodialysis.

A retrospective descriptive analysis of patient adherence to dabigatran at a large academic medical center.

BACKGROUND: Clinical trials evaluating the efficacy of dabigatran followed a very strict protocol, which included close monitoring and follow-up. Patients followed in this controlled environment had an average medication possession ratio (MPR) greater than 0.95. However, very few studies have evaluated patient adherence to dabigatran in a real-world setting. Other studies of chronic medications indicate patients are not reliably adherent to twice daily regimens. Adherence to therapy is particularly important for direct thrombin inhibitors because there may be a risk of increased thromboembolic events associated with poor adherence to these agents.  OBJECTIVE: To identify the MPR for patients prescribed dabigatran at a large academic medical center and affiliated clinics.  METHODS: This retrospective descriptive study evaluated the MPR for patients prescribed dabigatran between January 1, 2012, and December 31, 2012. Patients included in this study had to receive dabigatran for a minimum of 3 months, have a primary care physician or cardiologist at the medical center or affiliated clinics, and must not use a mail order pharmacy. Patient MPR was calculated based on prescriptions picked up from the patient. RESULTS: After screening 400 patients, 159 patients met eligibility criteria. The mean MPR for the patients in this study was 0.63. Overall, 43% of the patients had an MPR of less than 0.80, and the mean MPR for this subgroup was 0.39 ± 0.27; 57% of the study population had an MPR of 0.80 or higher, with a mean MPR of 0.94 ± 0.08. There was a significantly higher proportion of men (67.7%, P = 0.0112) and a larger number of "as needed medications" prescribed (1.73 vs. 0.86, P = 0.0039) in patients with an MPR less than 0.80. There were 5 patients hospitalized during the study period (3 for bleeding, 1 for confusion, and 1 death not related to dabigatran therapy).  CONCLUSIONS: The relatively low mean MPR seen in this study may indicate that there is a need for improved anticoagulation services and follow-up for patients taking dabigatran.