Critical appraisal of dabigatran in the treatment of deep vein thrombosis and pulmonary embolism

Objective To compare the safety and efficacy of dabigatran to warfarin for the treatment of deep vein thrombosis and pulmonary embolism. Background Venous thromboembolism (VTE) is a disease comprised of two conditions: deep vein thrombosis and pulmonary embolism. VTE is a major cause of morbidity and mortality worldwide with an annual incidence estimated at 1–3 cases per 1,000 individuals. This incidence increases with age from 0.1 per 1,000 in adolescence to eight per 1,000 in those 80 years of age and older. As the proportion of patients 65 years of age and older expands, the number of patients presenting with VTE will also increase. Anticoagulation remains the cornerstone of VTE treatment. Traditionally, vitamin K antagonists have been used to minimize the risk of thrombus extension and for secondary prevention. Unpredictable pharmacokinetics and pharmacodynamics, routine monitoring, drug–food and drug–drug interactions, and potentially severe adverse events have all been cited as barriers to optimal care. Dabigatran has been proposed as a suitable alternative to warfarin therapy in the treatment of VTE. Therefore, a critical appraisal of dabigatran’s safety and efficacy is necessary to determine its role in therapy. Conclusion Dabigatran remains an alternative to warfarin therapy for the treatment of VTE. However, dabigatran also has distinct disadvantages that warrant consideration. Clinicians must ensure that drug characteristics align with patient characteristics to optimize patient outcomes

PCSK9 Inhibitors in Secondary Prevention – An Opportunity for Personalized Therapy

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of death worldwide. Low-density lipoprotein cholesterol (LDL-C) is the primary cause of ASCVD and reducing LDL-C levels with statin therapy significantly reduces ASCVD risk; however, significant residual risk remains. Two monoclonal antibodies (mAbs), alirocumab and evolocumab, that target proprotein convertase subtilisin/kexin-type 9 (PCSK9), reduce LDL-C levels by up to 60% when used in combination with statins and significantly reduce the risk of recurrent ASCVD events in both stable secondary prevention and acute coronary syndrome populations. Pre-specified analyses of recent randomized controlled trials have shed light on how best to prioritize these therapies to maximize their value in select high risk groups. These data have also informed recent clinical practice guidelines and scientific statements resulting in an expanded role for PCSK9-mAbs compared to previous guidelines, albeit there are notable differences between these recommendations. Ongoing research is exploring the long-term safety of PCSK9-mAbs and their role in the acute setting as well as patients without prior myocardial infarction or stroke. Novel therapies that inhibit PCSK9 synthesis via small interfering RNA, such as inclisiran, are also in development and may reduce LDL-C levels similar to PCSK9-mAbs but with less frequent administration. Nonetheless, the PCSK9-mAbs are a breakthrough therapy and warrant consideration in very-high risk patients who are most likely to benefit. Such a personalized approach can help to ensure cost-effectiveness and maximize their value

Pharmacological Approaches For the Management of Patients with Moderately Elevated Triglycerides (150-499 mg/dL)

Hypertriglyceridemia, defined as serum triglyceride (TG) levels \u3e 150 mg/dL, now affects over one-quarter of the U.S. adult population and is associated with an increased risk of atherosclerotic cardiovascular disease. Available guidelines for managing hypertriglyceridemia vary with respect to triglyceride thresholds and severity of disease. Lifestyle modifications and management of secondary causes (e.g., diabetes) remain the first step in managing hypertriglyceridemia, with pharmacotherapy reserved to reduce the risk of pancreatitis and/or further reduce TG levels. Several classes of lipid-lowering agents are available with variable TG-lowering efficacy. While there is no consensus regarding the choice of initial TG-lowering pharmacotherapy, there is general agreement that the decision depends on the degree of hypertriglyceridemia and atherosclerotic cardiovascular disease risk. This review will discuss available and emerging lipid-lowering therapies for the management of moderately elevated TG, defined as TG 150-499 mg/dL

Evolving Role of Non-Statin Therapy for the Management of Dyslipidemia and Cardiovascular Risk Reduction: Past, Present, and Future

A plethora of evidence supports the use of statin therapy for primary and secondary prevention of atherosclerotic cardiovascular disease (ASCVD), yet residual risk among high-risk patients receiving statin therapy remains high. Moreover, statin-associated muscle symptoms and other statin-associated adverse effects (e.g., increased risk of diabetes mellitus) limit the use of statins in high-risk patient populations. Of particular concern are individuals with established ASCVD, familial hypercholesterolemia (FH), or diabetes mellitus plus multiple ASCVD risk factors, all of whom require high-intensity statins, which are more commonly associated with an increased risk of adverse effects

Interleukin-1 blockade in heart failure with preserved ejection fraction: rationale and design of the Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2)

Heart failure with preserved ejection fraction (HFpEF) now accounts for the majority of con-firmed HF cases in the United States. However, there are no highly effective evidence-basedtreatments currently available for these patients. Inflammation correlates positively withadverse outcomes in HF patients. Interleukin (IL)-1, a prototypical inflammatory cytokine, hasbeen implicated as a driver of diastolic dysfunction in preclinical animal models and a pilot clini-cal trial. The Diastolic Heart Failure Anakinra Response Trial 2 (D-HART2) is a phase 2, 2:1 ran-domized, double-blind, placebo-controlled clinical trial that will test the hypothesis that IL-1blockade with anakinra (recombinant human IL-1 receptor antagonist) improves (1) cardiorespi-ratory fitness, (2) objective evidence of diastolic dysfunction, and (3) elevated inflammation inpatients with HFpEF (http://www.ClinicalTrials.gov NCT02173548). The co–primary endpointswill be placebo-corrected interval changes in peak oxygen consumption and ventilatory effi-ciency at week 12. In addition, secondary and exploratory analyses will investigate the effectsof IL-1 blockade on cardiac structure and function, systemic inflammation, endothelial function,quality of life, body composition, nutritional status, and clinical outcomes. The D-HART2 clinicaltrial will add to the growing body of evidence on the role of inflammation in cardiovascular dis-ease, specifically focusing on patients with HFpEF

Primary healthcare policy and vision for community pharmacy and pharmacists in the united states

© 2020, Grupo de Investigacion en Atencion Farmaceutica. All rights reserved. The United States (US) has a complex healthcare system with a mix of public, private, nonprofit, and for-profit insurers, healthcare institutions and organizations, and providers. Unlike other developed countries, there is not a single payer healthcare system or a national pharmaceutical benefits scheme/plan. Despite spending over USD 10,000 per capita in healthcare, the US is among the worst performers compared to other developed countries in outcomes including life expectancy at birth, infant mortality, safety during childbirth, and unmanaged chronic conditions (e.g., asthma, diabetes). Primary care is delivered by physicians and advanced practice providers (i.e., nurse practitioners and physician assistants) in a variety of settings including large health systems, federally qualified health centers or free clinics that provide care to the underserved, or specific facilities for veterans or American Indian and Alaska native peoples. Since 2010, primary care delivery has shifted toward providing patient-centered, coordinated, comprehensive care focused on providing proactive, rather than reactive, population health management, and on the quality, versus volume, of care. Community pharmacy comprises a mix of independently owned, chain, supermarket and mass merchant pharmacies. Community pharmacies provide services such as immunizations, medication therapy management, medication packaging, medication synchronization, point-of-care testing and, in specific states where legislation has been passed, hormonal contraception, opioid reversal agents, and smoking cessation services. There has been criticism regarding the lack of standard terminology for services such as medication synchronization and medication therapy management, their components and how they should be provided, which hampers comparability across studies. One of the main challenges for pharmacists in the US is the lack of provider status at the federal level. This means that pharmacists are not allowed to use existing fee-for-service health insurance billing codes to receive reimbursement for non-dispensing services. In addition, despite there being regulatory infrastructure in multiple states, the extent of service implementation is either low or unknown. Research found that pharmacists face numerous barriers when providing some of these services. State fragmentation and the lack of a single pharmacy organization and vision for the profession are additional challenges

Effects of Sodium-Glucose Cotransporter 2 Inhibitors on 24-Hour Ambulatory Blood Pressure: A Systematic Review and Meta-Analysis

Background-—Sodium-glucose cotransporter 2 (SGLT2) inhibitors are a novel class of antihyperglycemic agents that improve glycemic control by increasing glycosuria. Additional benefits beyond glucose lowering include significant improvements in seated clinic blood pressure (BP), partly attributed to their diuretic-like actions. Less known are the effects of this class on 24-hour ambulatory BP, which is a better predictor of cardiovascular risk than seated clinic BP. Methods and Results-—We performed a meta-analysis of randomized, double-blind, placebo-controlled trials to investigate the effects of SGLT2 inhibitors on 24-hour ambulatory BP. We searched all studies published before August 17, 2016, which reported 24-hour ambulatory BP data. Mean differences in 24-hour BP, daytime BP, and nighttime BP were calculated by a random-effects model. SGLT2 inhibitors significantly reduce 24-hour ambulatory systolic and diastolic BP by -3.76 mm Hg (95% CI, -4.23 to -2.34; I2=0.99) and -1.83 mm Hg (95% CI, -2.35 to -1.31; I2=0.76), respectively. Significant reductions in daytime and nighttime systolic and diastolic BP were also found. No association between baseline BP or change in body weight were observed. Conclusions-—This meta-analysis shows that the reduction in 24-hour ambulatory BP observed with SGLT2 inhibitors is a class effect. The diurnal effect of SGLT2 inhibitors on 24-hour ambulatory BP may contribute to their favorable effects on cardiovascular outcomes

Dietary Fat, Sugar Consumption, and Cardiorespiratory Fitness in Patients With Heart Failure With Preserved Ejection Fraction

Heart failure with preserved ejection fraction (HFpEF) is associated with obesity and, indirectly, with unhealthy diet. The role of dietary components in HFpEF is, however, largely unknown. In this study, the authors showed that in obese HFpEF patients, consumption of unsaturated fatty acids (UFA), was associated with better cardiorespiratory fitness, and UFA consumption correlated with better diastolic function and with greater fat-free mass. Similarly, mice fed with a high-fat diet rich in UFA and low in sugars had preserved myocardial function and reduced weight gain. Randomized clinical trials increasing dietary UFA consumption and reducing sugar consumption are warranted to confirm and expand our findings