Direct Oral Anticoagulants and Prosthetic Heart Valves: A Systematic Review of Case Reports

Background: Direct oral anticoagulants (DOACs) are indicated to treat and prevent venous thromboembolism and to prevent stroke or systemic embolism in patients with non-valvular atrial fibrillation. The introduction of DOACs has provided an alternative to warfarin for patients in need of oral anticoagulation. It is, however, unclear whether DOACs are safe and effective in patients with heart valve replacement. The RE-ALIGN trial published in 2013 did not support the use of dabigatran in patients with mechanical valve replacements; however, there are ongoing studies, such as the PROACT Xa trial and the ATLANTIS trial, investigating the use of other DOACs in patients with heart valve replacements. This study is to evaluate and describe a potential risk of valve thrombosis in patients with heart valve replacement and treated with a DOAC. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, a systematic literature search was performed on June 24th, 2020 using three electronic databases (Pubmed, Embase, Cochrane Library) with the following key terms: (apixaban OR rivaroxaban OR edoxaban OR dabigatran OR direct oral anticoagulant OR factor Xa inhibitor OR direct thrombin inhibitor OR target specific oral anticoagulant) and (valve replacement OR valve implantation). Duplicates were removed automatically by Endnote and Rayyan QCRI. Two authors independently screened the search result using Rayyan QCRI (a systematic review web app). Different decisions were resolved through consensus between the two authors with the input of the third author. Pooled case reports were assessed and reported using descriptive analysis. Results: Of the initial 967 citations, 19 case reports involving 22 patients were identified and assessed in this study. 45.5%, 31.8%, and 22.7% of the patients were taking dabigatran, rivaroxaban, and apixaban, respectively. 11 patients (50%) had mechanical valves, and 11 patients (50%) had bioprosthetic valves. The average age of the patients was 65.2 years (SD±14.3) with 54.5% female. 59.1% of the patients had another indication for anticoagulation other than heart valve replacement. Of those patients, 92.3% had atrial fibrillation, and 7.7% had deep vein thrombosis. 13.6% of the cases reported concurrent aspirin use. 3 patients (13.6%) had cancer as a comorbid condition, and 1 patient (4.5%) had a valve-in-valve replacement. 95.5% of the 21 cases reported an intervention with 13 patients (61.9%) receiving surgery (11 valve replacements, 2 thrombectomies) and 8 patients (38.1%) receiving medical management. 4.5% of the cases reported death prior to intervention. The time reported from onset of DOAC therapy to onset of thrombotic event ranged from 9 days to 33 months. Conclusions: It is still uncertain whether DOACs are safe or effective in preventing valve thrombosis for different types of valve replacements. The use of DOACs in patients with valve replacement should be limited to those with no other alternative. Further research is needed to determine the effectiveness and safety of DOAC use in patients with prior valve replacements

Implementing a Monitoring Program for Patients on Direct Oral Anticoagulants

Service or Program: The Backus Hospital Medication Management Clinic located in Norwich, CT provides a newly implemented Direct Oral Anticoagulant (DOAC) management service. This service is provided by a clinical pharmacist for patients with non-valvular atrial fibrillation or venous thromboembolism. The clinical pharmacist assists in the initiation, monitors for the efficacy and safety, and provides education on the benefits and risks of DOAC therapy. The clinical pharmacist communicates to the referring physicians on any significant concerns or recommendations with DOAC therapy. Lifestyle, renal function, and other medication use will be evaluated to ensure safety and stability. The referred patients will be discharged from the clinic when they have been on DOAC for an extended duration (typically \u3e6 months). Prior to discharge, the patients will be assessed to ensure that they are well-educated on signs and symptoms of adverse events to DOAC agents and what actions to take if these events were to arise. Justification/Documentation: Many providers choose a DOAC for anticoagulation because of the ease of administration and fewer drug and food interactions compared to warfarin. However, they forego any follow-up with patients on DOAC agents believing it is unwarranted. On the contrary, a growing body of evidence and expert opinion supports the importance of follow-up monitoring for these patients. Pharmacists can intervene and improve the patients’ adherence, monitor for adverse events, and potentially improve their outcomes. Adaptability: This DOAC management service can be implemented in pharmacist-driven anticoagulation clinics. Many anticoagulation clinics are already staffed with healthcare professionals, who are well trained at evaluating and educating patients for the signs and symptoms of thrombosis and bleeding. The same concept along with renal function monitoring is applied in this DOAC management program. Significance: The role of a clinical pharmacist is expanding rapidly in the healthcare world. Pharmacist are now viewed as a valuable member of a healthcare team. This new DOAC management program is following this trend of expanding the pharmacist’s role. With the increased use of DOAC agents, pharmacist’s expanded service will redefine anticoagulation care

Sodium-Glucose Cotransporter 2 Inhibitors: An Overview

The management of type 2 diabetes (T2DM) has evolved significantly over the past several decades. One of the newest additions to antidiabetic therapy is a sodium-glucose cotransporter 2 (SGLT2) inhibitor with a unique mechanism that targets the kidney’s ability to reabsorb filtered glucose. In addition to providing glycemic control, this class has a unique mechanism of action associated with blood pressure reduction, weight loss, and potential cardiovascular benefits; however, the FDA is closely monitoring the use of these drugs based on increased safety concerns. The benefits and risks of SGLT2 inhibitors should be carefully considered. Selected patients with T2DM can benefit from SGLT2 inhibitor therapy

Improved learning experience with modified case studies courses in a pharmacy curriculum

Background and purpose Many pharmacy programs have dedicated case studies (CS) courses; however, universal standards on how to implement CS courses do not exist. Understanding the process of changing CS courses at an institution may help others to recognize and overcome potential barriers. This study describes the implementation process of changes that occurred in CS courses and evaluates the impact of the changes on students\u27 learning experiences. Educational activity and setting Faculty members involved in CS courses made changes that focused on small group discussions, increasing faculty availability, decreasing student-to-faculty ratio, providing immediate and detailed feedback, and facilitating active learning. After the implementation of the new CS course design, two surveys were administered to evaluate the impact of the new design, one to a single cohort of pharmacy students and one to faculty involved in the CS courses. Findings Seventy-two students completed the survey (80% response rate). The majority of students preferred the following aspects of the new CS course design: more objective SOAP (subjective, objective, assessment, plan) note rubric with detailed descriptions on point allocation, small group discussion within a classroom, and faculty-facilitated case review in group discussion. Having the same, readily available instructors reviewing a case in each class was also an important factor in their learning experience. The faculty survey resulted in similar findings but with concerns of increased workload and teaching an unfamiliar topic. Summary Overall, the new CS course design provided a better learning experience for pharmacy students compared to the previous CS course design

Self-Assembled Coatings for Controlling Biomolecular Adsorption on Surfaces

We have investigated a series of molecular and polymeric approaches for generating adherent thin films that impart anti-fouling characteristics to oxide surfaces. These films incorporate oligo- or poly(ethylene glycol) moieties that are expressed in high density in the near-surface region. In our molecular approach, oligo(ethylene glycol)-terminated n-alkyl-trichlorosilanes, RO(CH₂CH₂O)₃(CH₂)₁₁SiCl₃, have been designed so to spontaneously adsorb onto oxide surfaces and produce densely packed films. Another strategy uses a surface initiated polymerization to generate reactive anchored polymer chains that are then chemically modified to incorporate oligo(ethylene glycol) units. Lastly, a comb copolymer comprising a poly(acrylic acid) backbone and different grafting ratios of a linear poly(ethylene oxide-r-propylene oxide) chain has been prepared that adsorbs onto surfaces and forms a poly(ethylene glycol)-exposing film in single step. These surface coatings provide varying levels of protein and cellular resistance that can be related to molecular-scale elements of their surface structure.Singapore-MIT Alliance (SMA

Effect of Ezetimibe Added to High-intensity Statin Therapy in Patients with Hypercholesterolemia: A Meta-Analysis

Background: It is unknown whether the conclusion of the IMPROVE-IT trial can be extrapolated into patients taking high intensity statin plus ezetimibe. Therefore, a meta-analysis was performed to evaluate the impact of ezetimibe combined with high intensity statin on low-density lipoprotein cholesterol (LDL-C) levels in patients with hypercholesterolemia. Methods: A systematic literature search was performed using PubMed and EMBASE and restricted to randomized controlled trials (RCTs) in patients with hypercholesterolemia. The outcome of this analysis was mean difference in LDL-C reduction in patients treated with high intensity statin plus ezetimibe compared to corresponding high intensity statin. Results: Of the 404 citations, six RCTs involving 714 patients were included. Compared to the high intensity statin group, overall the mean difference in LDL-C reduction with high intensity statin plus ezetimibe was -12.07% (95% CI: -2.16 to -21.97; p=0.02). The results were associated with substantial heterogeneity (I2=84%, p\u3c0.00001). Notably, the mean difference in LDL-C reduction was decreased to -8.6% (95% CI: -4.22 to -12.98; p=0.0001) with non-significant heterogeneity (p=0.27, I2=22%) when the Robinson 2014 study was omitted. Conclusion: Among patients with hypercholesterolemia, adding ezetimibe to high intensity statin led to a mild but significant additional reduction in LDL-C levels compared to high intensity statin monotherapy

Molecular Phenotyping Small (Asian) versus Large (Western) Plaque Psoriasis Shows Common Activation of IL-17 Pathway Genes but Different Regulatory Gene Sets.

Psoriasis is present in all racial groups, but in varying frequencies and severity. Considering that small plaque psoriasis is specific to the Asian population and severe psoriasis is more predominant in the Western population, we defined Asian small and intermediate plaque psoriasis as psoriasis subtypes and compared their molecular signatures with the classic subtype of Western large plaque psoriasis. Two different characteristics of psoriatic spreading-vertical growth and radial expansion-were contrasted between subtypes, and genomic data were correlated to histologic and clinical measurements. Compared with Western large plaque psoriasis, Asian small plaque psoriasis revealed limited psoriasis spreading, but IL-17A and IL-17-regulated proinflammatory cytokines were highly expressed. Paradoxically, IL-17A and IL-17-regulated proinflammatory cytokines were lower in Western large plaque psoriasis, whereas T cells and dendritic cells in total psoriatic skin area were exponentially increased. Negative immune regulators, such as CD69 and FAS, were decreased in both Western large plaque psoriasis and psoriasis with accompanying arthritis or obesity, and their expression was correlated with psoriasis severity index. Based on the disease subtype comparisons, we propose that dysregulation of T-cell expansion enabled by downregulation of immune negative regulators is the main mechanism for development of large plaque psoriasis subtypes