Tyan Thomas

Rivaroxaban: an oral factor Xa inhibitor.

BACKGROUND Currently available anticoagulants utilized for venous thromboembolism (VTE) treatment and prevention and stroke prevention in patients with atrial fibrillation (AF) have proven effectiveness but are not optimally utilized because of barriers such as the need for subcutaneous administration and requisite routine laboratory monitoring. Rivaroxaban, a novel oral Xa inhibitor, is an alternative to standard therapies utilized for VTE prevention after elective orthopedic surgery, primary and secondary stroke prevention in nonvalvular AF, VTE treatment after an acute VTE event, and secondary prevention after the acute coronary syndromes (ACS). OBJECTIVE This article reviews the pharmacology, efficacy, and tolerability of rivaroxaban for VTE prophylaxis in post-orthopedic surgery and medically ill patients, stroke prevention in nonvalvular AF, adjunctive therapy in patients with ACS, and VTE treatment. METHODS International Pharmaceutical Abstracts and EMBASE were searched for English-only clinical trials and reviews published between 1970 and March 15, 2012. PubMed was searched for articles published between 1970 and June 30, 2012. Additional trials and reviews were identified from the citations of published articles. RESULTS Eighty-nine publications were identified: 10 clinical trials and 1 meta-analysis were used to obtain efficacy and tolerability data, and 1 analysis of pooled data from the clinical trials was included; 17 pharmacokinetic, pharmacodynamic, and drug-drug interaction studies were included; and 5 cost-analyses were reviewed. These data showed rivaroxaban to be noninferior to enoxaparin for thromboprophylaxis of VTE after total knee and total hip replacement surgery. It was also shown to be noninferior to vitamin K antagonist therapy for primary and recurrent stroke prevention in nonvalvular AF as well as for the treatment of VTE after an acute deep vein thrombosis or pulmonary embolism. It also showed benefit in lowering the risk for major adverse cardiovascular events after ACS. Differences in major bleeding rates were not statistically significant between rivaroxaban and comparators across the various studies, with the exception of ACS, in which there were higher rates of non-coronary artery bypass graft surgery related bleeding and intracranial hemorrhage. CONCLUSIONS Based on the findings of the studies reported in this review, rivaroxaban is an effective option for the prevention of VTE after orthopedic surgery, stroke prevention for nonvalvular AF, and treatment of VTE. At this time, rivaroxaban cannot be recommended for secondary risk reduction after ACS because of the increased bleeding risk.

Pharmacists implementing transitions of care in inpatient, ambulatory and community practice settings

Objective To introduce pharmacists to the process, challenges, and opportunities of creating transitions of care (TOC) models in the inpatient, ambulatory, and community practice settings. Methods TOC literature and resources were obtained through searching PubMed, Ovid, and GoogleScholar. The pharmacist clinicians, who are the authors in this manuscript are reporting their experiences in the development, implementation of, and practice within the TOC models. Results Pharmacists are an essential part of the multidisciplinary team and play a key role in providing care to patients as they move between health care settings or from a health care setting to home. Pharmacists can participate in many aspects of the inpatient, ambulatory care, and community pharmacy practice settings to implement and ensure optimal TOC processes. This article describes establishing the pharmacist’s TOC role and practicing within multiple health care settings. In these models, pharmacists focus on medication reconciliation, discharge counseling, and optimization of medications.[a sentence was deleted] Conclusion Optimizing the TOC process, reducing medication errors, and preventing adverse events are important focus areas in the current health care system, as emphasized by The Joint Commission and other health care organizations. Pharmacists have the unique opportunity and skillset to develop and participate in TOC processes that will enhance medication safety and improve patient care.

Frequency of Attainment of Low-Density Lipoprotein Cholesterol and Non-High-Density Lipoprotein Cholesterol Goals in Cardiovascular Clinical Practice (from the National Cardiovascular Data Registry PINNACLE Registry).

Studies have found that non-high-density lipoprotein cholesterol (non-HDL-C) is a superior marker for coronary heart disease compared to low-density lipoprotein cholesterol (LDL-C). Little is known about achievement of non-HDL-C goals outside clinical trials. Within a population of 146,064 patients with dyslipidemia in the PINNACLE Registry and a subgroup of 36,188 patients with diabetes mellitus (DM), we examined the proportion of patients and patient characteristics associated with having LDL-C, non-HDL-C, and both LDL-C and non-HDL-C levels at National Cholesterol Education Program goals. LDL-C, non-HDL-C, and both LDL-C and non-HDL-C goals in the overall cohort were achieved by 73%, 73.4%, and 68.9% patients, respectively. Significant predictors of meeting all 3 goals were age, male gender, statin, nonstatin, and combined statin plus nonstatin use. Patients with co-morbidities of hypertension, previous stroke or transient ischemic attack, peripheral arterial disease, myocardial infarction, and smoking were less likely to have LDL-C, non-HDL-C, and both LDL-C and non-HDL-C levels at National Cholesterol Education Program goal. In the overall cohort, patients with DM were less likely to meet non-HDL-C and both LDL-C and non-HDL-C goals. In the subgroup of patients with DM, predictors of meeting lipid goals were similar to the overall cohort. In conclusion, these data suggest contemporary treatment patterns by cardiologists successfully achieve lipid goals in most patients. Younger, female patients and those with atherosclerotic cardiovascular disease and risk factors, such as hypertension and DM, are less likely to achieve goals and may require more careful follow-up after statin initiation. Both LDL-C and non-HDL-C goals are achieved in <70% of patients, suggesting room for improvement if a goal-targeted individualized strategy is adopted.

Implications of incretin-based therapies on cardiovascular disease.

Incretin‐based therapies offer another treatment option for patients with type 2 diabetes. Agents that provide glycaemic control in addition to attenuating cardiovascular disease (CVD) risk factors are important for diabetes management. This review will focus on the off‐target effects of incretin‐based therapies on CVD risk factors [body weight, blood pressure (BP), lipid profile and albuminuria], major adverse cardiovascular events (MACE), heart failure (HF) and beta‐cell preservation.

Role of Novel and Emerging Oral Anticoagulants for Secondary Prevention of Acute Coronary Syndromes

Dual antiplatelet therapy has become a mainstay of long‐term management of patients after an acute coronary syndrome (ACS). Mortality for these patients remains high despite current evidence‐based treatment strategies. The coagulation cascade plays a role in the pathophysiology of ACS, and trials with warfarin in combination with dual antiplatelet therapy have found decreased rates of ischemic events at the expense of increased bleeding risk. Novel oral anticoagulants (NOACs) in the direct factor Xa (FXa) inhibitor and direct thrombin inhibitor (DTI) categories have been evaluated in combination with standard post‐ACS therapy. Rivaroxaban, a FXa inhibitor, reduced the rates of ischemic events but increased major bleeding rates. Apixaban did not decrease the rates of ischemic events and also increased major bleeding rates. Other FXa inhibitors have not been studied in the long‐term management of ACS (e.g., otamixaban), are not currently being studied in ongoing phase III trials (e.g., TAK‐442), or have been discontinued by the manufacturer (e.g., darexaban). The DTI dabigatran had a 2‐ to 4‐fold increased risk of major bleeding with unclear benefit for reducing ischemic events. The factor IXa inhibitor pegnivacogin is an RNA‐based aptamer that has been studied in patients undergoing cardiac catheterization but has not been studied for long‐term post‐ACS management. The European Society of Cardiology Working Group on Thrombosis recommends the use of newer antiplatelet agents over addition of NOACs. Additional guidelines are available to guide management in patients requiring triple antithrombotic therapy but do not provide definitive recommendations on NOACs. Many questions remain about the place of NOACs for long‐term post‐ACS management. Recent trials have evaluated double versus triple antithrombotic therapy to balance efficacy and bleeding risk, but they did not include NOACs. It also remains unclear if NOACs hold a place in post‐ACS therapy in the era of more potent antiplatelet agents such as prasugrel and ticagrelor.

Attainment of combined optimal lipid values: a paradigm shift in the management of dyslipidemia

Abstact Despite the documented benefits of appropriate dyslipidemia management in a multitude of different trial designs, there continues to exist a significant amount of residual cardiovascular risk in both clinical trial and real-world patients even after their LDL-C is controlled. In this article, we explore recent trial data that assess cardiovascular risk reduction associated with high-risk patients when single and multiple lipid fraction targets are attained. Data from these trials demonstrate that more complete control of all-lipid fractions in an individual’s lipid panel may result in additional reductions in cardiovascular risk. Despite these potential benefits, recent analyses show that few patients are being aggressively managed, as demonstrated by the low numbers of patients who are attaining optimal levels of all major lipid parameters. This lack of adequate lipid control presents a potentially significant opportunity to attain increased cardiovascular risk control through improved dyslipidemia management.

Attainment of combined optimal lipid values with the use of niacin: has AIM-HIGH closed the book on this debate?

Abstract The AIM-HIGH study results have provided new information for the clinical question regarding the potential benefit of the attainment of optimal lipid values to reduce residual cardiovascular risk in patients on optimal statin therapy. At first glance, it would seem that the early termination of this study owing to the perceived clinical futility of niacin therapy has effectively closed the debate on this topic. However, it is imperative that the clinician probes deeper into the study design and results before coming to this conclusion. This report will review the AIM-HIGH results and the impact on the clinical practice of adding niacin to optimized statin therapy in order to reduce residual cardiovascular risk.