Management of Patients at Risk for and With Left Ventricular Thrombus: A Scientific Statement From the American Heart Association.

Despite the many advances in cardiovascular medicine, decisions concerning the diagnosis, prevention, and treatment of left ventricular (LV) thrombus often remain challenging. There are only limited organizational guideline recommendations with regard to LV thrombus. Furthermore, management issues in current practice are increasingly complex, including concerns about adding oral anticoagulant therapy to dual antiplatelet therapy, the availability of direct oral anticoagulants as a potential alternative option to traditional vitamin K antagonists, and the use of diagnostic modalities such as cardiac magnetic resonance imaging, which has greater sensitivity for LV thrombus detection than echocardiography. Therefore, this American Heart Association scientific statement was commissioned with the goals of addressing 8 key clinical management questions related to LV thrombus, including the prevention and treatment after myocardial infarction, prevention and treatment in dilated cardiomyopathy, management of mural (laminated) thrombus, imaging of LV thrombus, direct oral anticoagulants as an alternative to warfarin, treatments other than oral anticoagulants for LV thrombus (eg, dual antiplatelet therapy, fibrinolysis, surgical excision), and the approach to persistent LV thrombus despite anticoagulation therapy. Practical management suggestions in the form of text, tables, and flow diagrams based on careful and critical review of actual study data as formulated by this multidisciplinary writing committee are given.

Sodium-Glucose Cotransporter 2 Inhibitors Among Heart Failure With Mildly Reduced and Preserved Ejection Fraction.

OBJECTIVE: Results from large placebo-controlled randomized trials in patients with heart failure with mid-range ejection fraction (HFmrEF) and HF with preserved EF (HFpEF) have become available recently. This article discusses results of these clinical trials. DATA SOURCES: Peer-reviewed articles were identified from MEDLINE (1966 to December 31, 2022) using search terms dapagliflozin, empagliflozin, SGLT-2Is, HFmrEF, and HFpEF. STUDY SELECTION AND DATA EXTRACTION: Eight completed, pertinent clinical trials were included. DATA SYNTHESIS: EMPEROR-Preserved, and DELIVER demonstrated that empagliflozin and dapagliflozin reduce CV death and heart failure hospitalization (HHF) in patients with HFmrEF and HFpEF, with/without diabetes when added to a standard heart failure (HF) regimen. The benefit is primarily due to reduction in HHF. Additional data from post hoc analyses of trials of dapagliflozin, ertugliflozin, and sotagliflozin suggest that these benefits may be a class effect. Benefits appear greatest in patients with left ventricular ejection fraction 41% up to about 65%. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: While many pharmacologic treatments have been proven to reduce mortality and improve cardiovascular (CV) outcomes in people with HFmrEF and HF with reduced EF (HFrEF), there are few therapy which improve CV outcome in people with HFpEF. SGLT-2I become one of the first class of pharmacologic agent that can be used to reduce HHF and CV mortality. CONCLUSION: Studies showed that empagliflozin and dapagliflozin reduce the combined risk of CV death or HHF in patients with HFmrEF and HFpEF when added to a standard HF regimen. Given that benefit has now been demonstrated across the spectrum of HF, SGLT-2Is should be considered one of the standard HF pharmacotherapy.

Focused Updates: SGLT2 Inhibitors in Patients With Heart Failure and/or Chronic Kidney Disease.

Sodium-glucose cotransporter (SGLT2) inhibitors have demonstrated cardiovascular (CV) benefits in large-scale clinical trials of people who have type 2 diabetes and either established CV disease or multiple CV risk factors. These studies also indicated early signals in benefiting heart failure (HF) patients and those with chronic kidney diseases. This article reviews recent and future clinical studies that focus on evaluation of the use of SGLT2 inhibitors in HF management and renal protection.

Managing Diabetes and Preventing Heart Disease: Have We Found a Safe and Effective Agent?

OBJECTIVE: While improving glycemic control with antihyperglycemics has been demonstrated to reduce microvascular complications, the benefits of reduction in cardiovascular diseases (CVDs) have not been demonstrated with older agents. This article reviews current evidence of the CV outcomes of newer antihyperglycemics approved since 2008. DATA SOURCES: Peer-reviewed articles were identified from MEDLINE (1966 to October 31, 2018) using search terms exenatide, liraglutide, lixisenatide, dulaglutide, semaglutide, alogliptin, linagliptin, saxagliptin, sitagliptin, canagliflozin, dapagliflozin, empagliflozin, mortality, myocardial infarction (MI), heart failure (HF), and stroke. STUDY SELECTION AND DATA EXTRACTION: A total of 12 pertinent double-blinded randomized controlled trials were included. DATA SYNTHESIS: Liraglutide, empagliflozin, and canagliflozin have been shown in patients with CV diseases and high risk of developing CV disease to be superior to placebo in improving CV outcomes. Saxagliptin and alogliptin have both been demonstrated to increase HF hospitalization, whereas sitagliptin has not. Relevance to Patient Care and Clinical Practice: In contrast to older-generation antihyperglycemics, selected new antihyperglycemic agents have been shown to be superior to placebo in improving CV outcomes. Clinicians may now be able to provide high-risk patients agents that not only help in providing glycemic control, but also prevent both macrovascular and microvascular complications. CONCLUSION: Liraglutide, empagliflozin, and canagliflozin have been shown to be superior to placebo in improving CV outcomes. However, there are differences among agents in terms of HF and peripheral arterial disease outcomes. Future studies should focus on evaluating other clinical CV outcomes in patients without existing CVD and perhaps single drug regimens for diabetes.

Translating Guidelines Into Practice: Interpreting the 2016 ACC Expert Consensus Decision Pathway on the Role of Non-Statin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk.

OBJECTIVE: In 2016, the American College of Cardiology released a decision pathway, based on expert consensus, to guide use of non-statin agents in the management of atherosclerotic cardiovascular disease risk. The purpose of this article is to assist practitioners, health systems and managed care entities with interpreting this consensus statement in order to simplify implementation of the recommendations into patient care. METHODS: Major themes from the consensus statement are briefly summarized and explained. Drug therapy recommendations are condensed into a single algorithm, while tables correlate each recommended regimen with the appropriate patient population from both a patient-level and systems-level perspective. Finally, a patient case with evidence-based decision support is explored. RESULTS: These tools allow practitioners to make appropriate patient-specific decisions about the use of non-statin pharmacotherapy and enable health systems and managed care entities to more readily identify guideline-appropriate use of these agents upon review of patient profiles or prescribing patterns. CONCLUSION: This article provides resources for healthcare providers that facilitate uptake of these recommendations into clinical practice.

What's next for dyslipidemia management? The 2013 ACC/AHA Guidelines, the NLA recommendations, and beyond.

OBJECTIVES: To compare and contrast the 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guidelines and the 2014/2015 National Lipid Association (NLA) Recommendations for Management of Dyslipidemia in the context of evolving evidence. DATA SOURCES: Guidelines from the National Cholesterol Education Program (NCEP), ACC/AHA, and NLA; recent clinical trials involving non-statin therapies. STUDY SELECTION: Not applicable. DATA EXTRACTION: At the authors' discretion, preference was given to references focusing on guidelines and recent clinical trials involving dyslipidemia management. RESULTS: In late 2013, the ACC/AHA released guidelines on the treatment of blood cholesterol to reduce risk for atherosclerotic cardiovascular disease (ASCVD) in adults. Reflecting contemporary evidence-based literature, low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C) numeric treatment goals were eliminated, and a new method of risk assessment (the Pooled Cohort Equations) was recommended. The guidelines emphasized lipid lowering in 4 patient populations proven to benefit from statin therapy, recommending moderate to high-intensity statin dosing, with no additional drug therapies and limited ongoing monitoring. Clinical controversies ignited by these guidelines led to the publication of recommendations by the NLA in 2014 and 2015. Part 1 of the NLA recommendations incorporated parts of both the ATP III guidelines and the 2013 ACC/AHA guidelines along with updated original recommendations. These recommendations provided numeric LDL-C, non-HDL-C, and apolipoprotein B treatment goals and potential additional ASCVD risk factors, with stepwise risk assessment based on traditional cardiac risk factors and multiple assessment tools. In addition to statins, the 2014 NLA recommendations highlighted the benefit of additional or alternative lipid-lowering therapies. Part 2 of the NLA recommendations expanded the guidance for treatment of special populations and prioritized ezetimibe as a non-statin agent based on recent evidence. Finally, the US Food and Drug Administration recently approved 2 medications from a new class, the PCSK9 inhibitors, although their role in therapy remains unclear pending outcomes data. CONCLUSION: We aim to highlight the core recommendations of recent guideline publications and to discuss similarities and differences in the context of the future management of dyslipidemia.

Vorapaxar in atherosclerotic disease management.

OBJECTIVE: To review the pharmacology, efficacy, and safety of vorapaxar, a protease activator receptor-1 (PAR-1) antagonist, in the management of atherosclerotic diseases. DATA SOURCES: Peer-reviewed clinical trials and review articles were identified from MEDLINE and Current Content database (both 1966 to December 31, 2014) using the search terms vorapaxar and protease activator receptor antagonist. STUDY SELECTION AND DATA EXTRACTION: A total of 30 clinical studies were identified (16 clinical trials, including subanalyses, 14 related to pharmacology, pharmacokinetics, and pharmacodynamics and drug interactions). DATA SYNTHESIS: Two phase III clinical trials with vorapaxar have been published. In patients with non-ST segment elevation myocardial infarction (MI), vorapaxar failed to significantly reduce the primary efficacy end point (composite of cardiovascular death, MI, stroke, recurrent ischemia with hospitalization, and urgent coronary revascularization). Conversely, in a study of secondary prevention for patients with cardiovascular disease, the composite end point of cardiovascular death, MI, or stroke was significantly reduced. In both trials, the safety end points of major/minor bleeding were increased compared with placebo. In the secondary prevention trial, an increased incidence of intracranial hemorrhage led to the exclusion of patients with a prior history of stroke. CONCLUSION: Vorapaxar is approved for use with aspirin and/or clopidogrel in the secondary prevention of cardiovascular events in stable patients with peripheral arterial disease or a history of MI. However, the addition of vorapaxar to other antiplatelets can significantly increase the risk of bleeding. It is, therefore, essential to balance the need for further reduction of risk of thrombotic event with patient's individual bleeding risk.

A Description of Required NAPLEX Preparation Courses Among US Pharmacy Programs.

OBJECTIVE: One of the final tasks for pharmacy graduates to enter practice is passing the North American Pharmacist Licensure Examination (NAPLEX). Given the recent national declines in pass rates, programs are making significant investments of time and money in NAPLEX preparation. The objective is to characterize the structure and content of required NAPLEX preparation courses. METHODS: A survey on NAPLEX preparation practices was developed and distributed to all Accreditation Council for Pharmacy Education-accredited pharmacy schools. NAPLEX preparation course syllabi were also collected as part of this survey. Syllabus information was summarized into 4 elements: course structure, content, resources, and assessment strategies. RESULTS: Of 144 colleges/schools of pharmacy, 100 responded to the survey, 87 reported having a NAPLEX preparation program, and 47 reported having a NAPLEX preparation course. Twenty syllabi were collected. Most courses (14) were longitudinal through the Advanced Pharmacy Practice Experiences year, 16 were credit-bearing, and 19 included a vendor NAPLEX preparatory product. Fourteen courses were hybrid delivery, and 12 focused on licensure preparation and included test-taking strategies, calculations practice, case-based discussions, etc. All 20 courses reported using unproctored timed quizzes and practice examinations, half conducted proctored timed assessments, and 11 included written reflections and/or continuous professional development activities. Most courses were pass/fail (15), and high stakes (16) were defined by delayed or withheld graduation as a consequence for failure. Only 3 of 20 NAPLEX preparation courses were mapped to NAPLEX competencies. CONCLUSION: Although required NAPLEX preparation courses focus on assessments, the content is infrequently mapped to NAPLEX competencies. This project provides some information on how schools might create their own NAPLEX preparatory courses.

An observational study of ezetimibe in cardiac transplant recipients receiving calcineurin inhibitors.

BACKGROUND: Cardiac transplant patients are at risk for developing cardiac allograft vasculopathy, and dyslipidemia in this patient population has been associated with increased risk. Data evaluating the efficacy and safety of ezetimibe in this population are minimal. OBJECTIVES: The purpose of this study was to assess the effects of ezetimibe, alone or in combination with other lipid-lowering agents, in cardiac transplant recipients receiving calcineurin inhibitors (CNIs). METHODS: This study was a single-center retrospective chart review. Data on demographics, medications prescribed for dyslipidemia and prevention of transplant rejection, results of lipid panels, CNI blood concentrations, and adverse effects were extracted from medical records of cardiac transplant recipients who were prescribed ezetimibe, either alone or in combination with other lipid-lowering agents, and seen at least once in a 12-month period at a cardiac transplantation clinic of an 800-bed teaching hospital. RESULTS: There were 71 patients prescribed ezetimibe in whom a safety analysis was performed. Approximately 49% (n = 35) were included in the analysis for lipid lowering. Ezetimibe significantly decreased low-density lipoprotein cholesterol (LDL-C; 129 mg/dL vs 94 mg/dL, P < .0001), non-high-density lipoprotein cholesterol (non-HDL-C; 170 mg/dL vs 127.5 mg/dL, P = .0058), and total cholesterol (236 mg/dL vs 200 mg/dL, P < .0001). There was no significant change in HDL-C and triglycerides as compared with baseline. The proportion of patients achieving goal LDL-C < 100 mg/dL significantly increased from 11.5% at baseline to 60.5% after the addition of ezetimibe (P < .0001). Ezetimibe had no measurable effect on blood CNI concentrations or doses. Adverse effects were reported by 15.5% of patients (n = 11), with 4% (n = 3) of patients discontinuing therapy. The most common complaints were gastrointestinal intolerance and myalgia. CONCLUSIONS: Ezetimibe was associated with lower LDL-C in cardiac transplant recipients either as combination therapy in patients with elevated LDL-C or as monotherapy, with a low frequency of adverse effects.

NAPLEX Preparation Program Characteristics and Resources Associated With First-Time Exam Pass Rates.

OBJECTIVE: Pharmacy colleges and schools invest substantial faculty effort and financial resources in North America Pharmacist Licensure Exam (NAPLEX) preparation, including vendor products purported to improve NAPLEX pass rates. The objective of this project was to examine NAPLEX preparation program characteristics associated with first-time pass rates. METHODS: A national survey investigated which pharmacy schools provided a formal NAPLEX preparation program in the 2021/2022 academic year, and what resources students were required to use. Pharmacy school characteristics and the unique resources provided in NAPLEX preparation programs were separately analyzed for association with 2022 NAPLEX first-time pass rates. RESULTS: The survey response rate was 71% (100 pharmacy schools). Of the 6 pharmacy school characteristics analyzed, offering a formal NAPLEX preparation program and private status were both weakly correlated with a decrease in the 2022 NAPLEX pass rate, while founding year of 2000 or earlier was weakly correlated with an increase in the pass rate. In a generalized linear model, a decrease in 2022 NAPLEX pass rate was associated with offering a formal NAPLEX preparation program (-5.90% [-11.55 to -0.23]) and with a 3-year accelerated curriculum (-9.15% [-15.55 to -2.75]). Of 12 resources required in NAPLEX preparation programs, 3 were weakly correlated with a decrease in 2022 pass rate: a vendor question bank, vendor review book/materials, and a live, synchronous faculty-led review. In a generalized linear model, a decrease in 2022 NAPLEX pass rate was associated with a live, synchronous faculty-led review (-6.62% [-11.16 to -2.08]). Among schools without a formal preparation program, NAPLEX pass rates consistently exceeded the national average in 2020, 2021, and 2022, while the proportion of schools with NAPLEX preparation programs and first-time pass rates above the national average dropped from 59% in 2021 and 58% in 2020 to 44% in 2022. CONCLUSION: Simply implementing a NAPLEX preparation program is insufficient to overcome other systemic/programmatic influences of successfully passing the NAPLEX; programs should invest earlier resources to address NAPLEX competencies.

A Description of NAPLEX and MPJE Preparation Strategies Among US Colleges and Schools of Pharmacy.

OBJECTIVE: The purpose of this study was to describe the different strategies used to supplement North American Pharmacist Licensure Examination (NAPLEX) and Multistate Pharmacy Jurisprudence Examination (MPJE) preparation in the US pharmacy programs. METHODS: An online survey was developed to gather information from 141 accredited schools/colleges of pharmacy about the preparation methods used during the 2021-22 academic year. The questionnaire contained 19 NAPLEX- and 10 MPJE-specific questions related to timing, content, use of commercial products and programs, faculty involvement, and whether these activities were required or recommended. Characteristics of schools/colleges were compared based on the presence or absence of preparation programs; preparation programs were descriptively reported. RESULTS: The response rate was 71%. Most schools (87/100 respondents) provided NAPLEX preparation programs starting in the advanced pharmacy practice experiential year, required students to participate, and focused on reviewing the content instead of assessing students' examination readiness. Similar elements were reported among 61 schools providing MPJE preparation programs. Schools used a variety of resources including access to vendor-based question banks or review materials, and completing live, proctored, NAPLEX-like examinations. Characteristics of schools or colleges did not differ significantly based on presence or absence of a preparation program. CONCLUSION: Schools/colleges of pharmacy use a variety of strategies to prepare students for licensing examinations. Many require student participation in vendor-based preparation programs for NAPLEX, and homegrown programs for MPJE preparation. The next step will be to determine the effectiveness of various approaches used by the schools/colleges on first-time licensure examination attempts.

The role of apixaban for venous and arterial thromboembolic disease.

OBJECTIVE: To provide a comprehensive review of the pharmacology, pharmacokinetics, pharmacodynamics, clinical trial data, adverse effects, and drug interactions of apixaban. DATA SOURCES: An English-language literature search was performed with MEDLINE/PubMed from January 2007 to August 2011 using the search terms apixaban, factor Xa inhibitors, FXa inhibitors, BMS-562247-01, venous thromboembolism, deep vein thrombosis, pulmonary embolism, myocardial infarction, acute coronary syndrome, ACS, atrial fibrillation, atrial arrhythmias, total hip replacement or arthroplasty, total knee replacement or arthroplasty, and orthopedic surgery to identify relevant articles. The references of the retrieved articles, professional society meeting abstracts, and the Web site www.clinicaltrials.gov were reviewed to identify other pertinent articles. STUDY SELECTION AND DATA ABSTRACTION: Pertinent original studies involving apixaban's pharmacology, pharmacokinetics, drug interactions, and clinical efficacy and safety data were included. DATA SYNTHESIS: Results of 2 large Phase 3 trials suggest that apixaban is superior for stroke and systemic embolism prevention compared to both aspirin and warfarin in patients with atrial fibrillation (AF); rates of major bleeding and intracranial hemorrhage were similar to those of aspirin but significantly reduced compared to warfarin. Completed trials in orthopedic surgery found apixaban to be superior to enoxaparin in total hip replacement (THR) surgery but inferior in total knee replacement (TKR) surgery, with similar rates of major bleeding. A Phase 3 trial of apixaban in acute coronary syndrome was stopped early because of excess bleeding. Future Phase 3 trials will help to determine apixaban's role for treatment of deep vein thrombosis and pulmonary embolism. Currently, apixaban is approved only in Europe for prophylaxis of venous thromboembolism in adults who have undergone elective THR or TKR. CONCLUSIONS: A Phase 3 trial in patients with AF revealed apixaban to be superior to warfarin for stroke and systemic embolism prophylaxis, with lower rates of major bleeding. Further studies will help to confirm the role of apixaban for other indications.

P2Y12 receptor inhibitors: integrating ticagrelor into the management of acute coronary syndrome.

Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST-segment elevation ACS and ST-segment elevation myocardial infarction. The purpose of this article is to define the developing role of ticagrelor in ACS and compare it to currently available P2Y12 receptor inhibitors. While clopidogrel remains the "workhorse" P2Y12 receptor inhibitor for many patients with ACS and prasugrel has an established role in select situations, clinicians must now assimilate the evolving role of ticagrelor. Although ticagrelor offers important advances in the management of ACS (eg, reversibility), there are also notable clinical considerations (eg, unique adverse effects such as dyspnea). Based on the current evidence, we propose an algorithm to aid clinicians in the selection of a P2Y12 receptor inhibitor for patients with ACS in various clinical situations.

COVID-19 and thrombosis: From bench to bedside.

Coronavirus disease of 2019 (COVID-19) is the respiratory viral infection caused by the coronavirus SARS-CoV2 (Severe Acute Respiratory Syndrome Coronavirus 2). Despite being a respiratory illness, COVID-19 is found to increase the risk of venous and arterial thromboembolic events. Indeed, the link between COVID-19 and thrombosis is attracting attention from the broad scientific community. In this review we will analyze the current available knowledge of the association between COVID-19 and thrombosis. We will highlight mechanisms at both molecular and cellular levels that may explain this association. In addition, the article will review the antithrombotic properties of agents currently utilized or being studied in COVID-19 management. Finally, we will discuss current professional association guidance on prevention and treatment of thromboembolism associated with COVID-19.

Aspirin for primary prevention of cardiovascular disease: a review of recent literature and updated guideline recommendations.

INTRODUCTION: Recent clinical trials evaluating the efficacy of aspirin in primary prevention of atherosclerotic cardiovascular disease (ASCVD) have suggested the risk of aspirin may outweigh its benefit in individuals once thought to be candidates for aspirin therapy. These results led to the publication of updated guideline recommendations in 2019 for aspirin use in primary prevention of cardiovascular disease from the American College of Cardiology (ACC) and American Heart Association (AHA). AREAS COVERED: Recent clinical trials and guidelines relevant to aspirin for primary prevention of ASCVD were identified using PubMed® (July 1, 2016 to April 1, 2019). Studies were limited to randomized, controlled clinical trials. The most current clinical practice guidelines were prioritized. EXPERT OPINION: Recent clinical trials demonstrated an increased risk of bleeding associated with aspirin use, which often outweighed cardiovascular risk reduction. In light of this new evidence, the ACC/AHA guidelines recommend aspirin for primary prevention in patients 40-70 years of age at a high ASCVD risk and low bleeding risk, who are unable to optimally control modifiable ASCVD risk factors.

Implementation of a formal pharmacy residency research certificate program.

PURPOSE: We describe the structure, implementation, and initial evaluation of a formal residency research certificate program (RRCP) designed to further advance residents' knowledge and skills in research in an effort to better prepare residents for research involvement during their careers. SUMMARY: Pharmacy residency programs vary in the degree of emphasis on research education and training and the structure of resident research activities. Limited data describing formal research education and training for pharmacy residents are available. To better educate and prepare residents in the research process, State University of New York Upstate University Hospital developed and implemented a formal RRCP designed to educate and train residents in essential areas of the research process. Research seminars are delivered by preceptors with experience and training in research throughout the academic year to align with residency project tasks. Residents are also required to complete at least 1 residency project and submit a manuscript suitable for publication in a peer-reviewed journal. Upon successful completion of the program and project requirements, residents earn a certificate of completion. Initial data collected through formal resident assessments before and after RRCP completion demonstrated significant improvement in research knowledge (from an average score of 61.3% out of 100% to an average score of 84.7%, P = 0.002). CONCLUSION: Post-RRCP assessment showed improvements in residents' confidence in several areas of research, including but not limited to research project design, ethical and regulatory principles of research, data collection, selection of appropriate statistical tests, manuscript writing, and the publication process. Residents strongly agreed that the RRCP improved their overall knowledge and perceptions of research.

A benchmark for platelet count monitoring with low-molecular-weight heparin: expanding implementation of National Patient Safety Goals.

Practitioners in US hospitals are implementing anticoagulation dosing and monitoring protocols to improve the safety of anticoagulation, consistent with National Patient Safety Goal 03.05.01. An audit of the Utrecht Patient Oriented Database of patients treated with low-molecular-weight heparin (LMWH) at the University Medical Center Utrecht revealed low compliance with platelet count monitoring as well as initial management of suspected heparin-induced thrombocytopenia (HIT). Limitations to this work included the inability to exclude other drug-induced causes of thrombocytopenia and their definition of the frequency of platelet count monitoring for compliance in patients given venous thromboembolism prophylaxis. Despite these limitations, the authors' work represents the first published report on extending the quality of heparin anticoagulation management to platelet count monitoring and evaluation for HIT in a large patient population. Clinicians should include evaluations of compliance with platelet count monitoring with unfractionated heparin and LMWH, as well as appropriateness of the initial management strategies for HIT, and direct thrombin inhibitor protocols in their patient safety practice assessments.

Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings.

OBJECTIVE: To develop practical recommendations for the use of low-molecular-weight heparins (LMWHs) as prophylaxis and treatment of venous thromboembolism and acute coronary syndromes in patients with impaired renal function or obesity. DATA SOURCES: Multiple MEDLINE searches were performed (November 2008) to identify studies for inclusion, using a comprehensive list of search terms including, but not limited to, LMWH, enoxaparin, dalteparin, tinzaparin, obesity, weight, renal, kidney, elderly, monitoring, and anti-Xa. STUDY SELECTION AND DATA EXTRACTION: Only articles published in English that were relevant for this review were included. DATA SYNTHESIS: In the majority of patients, standardized prophylaxis or treatment doses of LMWHs can be used without the need for monitoring and adjusting regimens. For patients with severe renal impairment (estimated creatinine clearance [CrCl] <30 mL/min), doses of some LMWHs should be adjusted or unfractionated heparin should be used instead. CrCl should be estimated using the Cockcroft-Gault method. Differences are noted in the degree of accumulation of various LMWHs in patients with moderate-to-severe renal impairment, and thus, the degree of dose adjustment may differ among the various LMWHs. Increasing the prophylactic doses of LMWH may be appropriate in morbidly obese patients (body mass index > or = 40 kg/m(2)). The use of total body weight is appropriate for therapeutic doses of LMWH in obese patients. Laboratory monitoring of the anticoagulation effect of LMWHs is generally not necessary, but should be considered in patients with morbid obesity (weight >190 kg), those with severe renal impairment, and those with moderate renal impairment with prolonged (>10 days) LMWH use. When anti-Xa activity is monitored, it should be determined using a chromogenic method and a calibration curve based on the LMWH used. CONCLUSIONS: Additional data are needed for specific dose guiding in obese and renally impaired patients, who are often excluded from larger clinical trials. Practice recommendations are made based on available evidence and authors' clinical opinions.