Intravenous iron in patients with iron deficiency and heart failure: a review of modern evidence.

PURPOSE OF REVIEW: Iron deficiency is common in patients with heart failure, affecting up to half of ambulatory patients and an even greater percentage of patients admitted for acute decompensation. Iron deficiency in this population is also associated with poor outcomes, including worse quality of life in addition to increased hospitalizations for heart failure and mortality. Evidence suggests that patients with iron deficiency in heart failure may benefit from repletion with IV iron. RECENT FINDINGS: In this review, we outline the etiology and pathophysiology of iron deficiency in heart failure as well as various iron formulations available. We discuss evidence for intravenous iron repletion with a particular focus on recent studies that have evaluated its effects on hospitalizations and mortality. Finally, we discuss areas of uncertainty and future study and provide practical guidance for iron repletion. SUMMARY: In summary, there is overwhelming evidence that intravenous iron repletion in patients with iron deficiency in heart failure is both beneficial and safe. However, further evidence is needed to better identify which patients would most benefit from iron repletion as well as the ideal repletion strategy.

Iron Deficiency in Heart Failure: A Scientific Statement from the Heart Failure Society of America.

Iron deficiency is present in approximately 50% of patients with symptomatic heart failure and is independently associated with worse functional capacity, lower quality of, life and increased mortality. The purpose of this document is to summarize current knowledge of how iron deficiency is defined in heart failure and its epidemiology and pathophysiology, as well as pharmacological considerations for repletion strategies. This document also summarizes the rapidly expanding array of clinical trial evidence informing when, how, and in whom to consider iron repletion.

Management of Iron Deficiency in Heart Failure: A Review of Evidence.

ABSTRACT: Iron deficiency is common in patients with heart failure and has been associated with worse outcomes, including increases in mortality, disease progression, and hospitalizations. As such, several studies have evaluated the role of iron supplementation in mitigating these risks. Evidence for the role of intravenous iron in improving exercise capacity, quality of life, and hospitalizations is promising, although the benefits of oral iron remain less clear. This review will evaluate the literature surrounding iron supplementation in heart failure and provide practical recommendations for its management.

Continuation Versus Interruption of Renin-Angiotensin System Inhibitors in Acute Decompensated Heart Failure: A Brief Report.

This article is temporarily under embargo.

Selection by design: Using job analysis to guide the selection of postgraduate pharmacy residents.

PURPOSE: To help ensure that we were accurately and consistently evaluating applicants to our postgraduate year 1 (PGY1) pharmacy residency program, we performed a job analysis to inform a redesign of our selection process. SUMMARY: A diverse panel of subject matter experts from our program was convened to develop a task inventory; a list of knowledge, skills, abilities, and other characteristics necessary for success in our program; and behavioral snapshots representing especially strong or weak resident performance (ie, critical incidents). After achieving a priori thresholds of consensus, these items were used to augment our application screening instrument (eg, development of anchored rating scales), build an online supplemental application consisting of a personality test and situational judgment test, develop a work sample consisting of a patient case presentation, and enhance the structure of our interviews (eg, by asking a consistent pattern of questions for all candidates). Preceptors reported that the redesigned process was more organized, easier to complete, and facilitated greater rating consistency. CONCLUSION: Job analysis represents an approach to designing selection processes that are more valid, reliable, transparent, and fair. Based on our experiences, recommendations for those who are considering changes to their selection process are provided.

An inter-institutional PharmD elective course and qualitative analysis exploring student engagement and collaboration.

BACKGROUND AND PURPOSE: There are limited reports in the literature of integrated inter-institutional doctor of pharmacy (PharmD) coursework where learners and faculty are connected using synchronous web conferencing. Furthermore, the impact of this learning environment on student engagement and collaboration has not been reported previously. EDUCATIONAL ACTIVITY AND SETTING: Faculty members from two separate schools of pharmacy collaborated to create the Current Concepts and Controversies in Cardiology (C4) elective, a two-credit hour elective course that was delivered via synchronous web conferencing. The course was designed to build upon students' pre-existing cardiovascular knowledgebase using case-based discussions, critical appraisal of clinical trials, and pro/con debates. Qualitative analysis using semi-structured interviews was performed to explore aspects of the course that promoted, or hindered, students' engagement and collaboration. FINDINGS: Seven students completed the semi-structured interviews following completion of the course. Themes identified that promoted student engagement and collaboration included, but were not limited to, observing professional relationships and interactions among faculty as well as faculty specifically calling on students by name or location. Three themes were found to be barriers to engagement and collaboration across institutions and included glitches in technology, the adversarial setup of the pro/con debates, and the inability to partake in impromptu discussion before and after class. SUMMARY: The C4 elective course was an integrated inter-institutional PharmD elective delivered using web conferencing. We highlight aspects of the course that promoted engagement and collaboration. The impact of inter-institutional PharmD education remains largely unexplored but may be an area of future interest and research.

Initial non-adherence to antihypertensive medications in the United States: a systematic literature review.

An important component of hypertension management is the initiation and continuation of antihypertensive medications. Non-adherence during the long-term use of antihypertensive medications is well studied. However, there is a paucity of research about the frequency and clinical consequences of failing to take the first dose of an antihypertensive, a treatment challenge known as initial medication non-adherence (IMN). This systematic literature review summarizes the published evidence from 2010 to 2019 on the prevalence, associated factors, consequences, and solutions for IMN to antihypertensive medications in the United States. Of the fifteen studies identified, nine studies reported the prevalence of IMN, two studies examined patient-reported reasons for IMN, and four studies evaluated interventions aimed to lower IMN. It is estimated that 5-34% of patients do not obtain their new antihypertensive medications. Factors and reasons cited include patient demographics, patient beliefs or perceptions about medications, cost or financial barriers, and clinical characteristics, such as a new hypertension diagnosis or higher co-morbid disease burden. The clinical, economic, and patient-reported outcomes of IMN are not well researched. In addition, interventions to address IMN have yielded inconsistent results. Significant opportunities exist for further research into this dimension of patient behavior to better understand and address IMN to new antihypertensive medications.

Personality: A potentially untapped resource in the selection of postgraduate pharmacy residents.

PURPOSE: This study assessed whether personality testing of postgraduate year 1 (PGY1) pharmacy residency applicants was feasible and predicted important selection outcomes, including interview offers. METHODS: Applicants to the PGY1 pharmacy residency program at a large academic medical center were invited to complete a 50-item online personality test based on the 5-factor model (ie, the "Big Five"). Scores were sealed until after matching, at which point they were compared to screening, interview, and ranking and match outcomes. Endpoints of interest included the feasibility of the test (eg, time required for completion, completion rate) and whether personality predicted the odds of an interview offer. RESULTS: The personality test was taken by 137 PGY1 applicants (69.5%) and required a median of 6.8 minutes to complete. Openness to experience was associated with decreased odds of an interview offer (adjusted odds ratio [OR], 0.86; 95% confidence interval [CI], 0.75-0.98), whereas conscientiousness and extraversion were associated with increased odds of an interview offer (conscientiousness: adjusted OR, 1.26; 95% CI, 1.02-1.55; extraversion: OR, 1.16; 95% CI, 1.03-1.31). When combined with traditional screening criteria (eg, awards, leadership positions), openness to experience and extraversion remained predictors of an interview offer (in the directions specified above), whereas conscientiousness did not. In an exploratory analysis of interviewees, agreeableness was a negative predictor of interview score. Personality did not predict screening scores or final ranking. CONCLUSION: Personality testing, based on the traits desired at individual residency programs, could be a valuable addition to the methods used for selecting PGY1 pharmacy residents.

The Impact of Atherosclerotic Cardiovascular Risk on Graft Failure in Deceased-Donor Renal Transplantation.

INTRODUCTION: Pretransplant cardiovascular risk may be amplified after renal transplant, but little is known about its impact on graft outcomes. RESEARCH QUESTION: The purpose of this study was to determine if pretransplant cardiovascular risk was associated with graft outcomes. DESIGN: This retrospective study included deceased-donor renal transplant recipients from 2010-2015. Atherosclerotic cardiovascular disease risk for patients without prior disease was calculated and patients were categorized into high (score >20%), intermediate (7.5-20%), and low risk (<7.5%). Patients with and without prior cardiovascular disease were also compared. The main endpoint was graft failure at 3-years post-transplant. Other outcomes included major adverse cardiovascular events, biopsy-proven rejection, and mortality. RESULTS: In patients without prior atherosclerotic cardiovascular disease (N = 115), graft failure rates (4.5% vs 11.3% vs 12.5%; (P = 0.64) and major adverse cardiovascular events (9.1% vs 13.2% vs 5.0%; P = 0.52) were similar in the high, intermediate, and low risk groups. In those with prior disease (N = 220), rates of primary nonfunction (6.8% vs 1.7%; P = 0.04), major adverse cardiovascular events (7.3% vs 2.6%; P = 0.01), and heart failure (10.9% vs 3.5%; P = 0.02) were higher than those without cardiovascular; rates of major adverse cardiovascular events and heart failure were insignificant after adjusting for age, gender, and race. Other outcomes were not different. Outcomes did not differ based on pretransplant cardiovascular risk. DISCUSSION: Pretransplant atherosclerotic cardiovascular disease was associated with increased early graft failure but similar outcomes at 3-years, suggesting cardiac risk alone should not exclude transplantation.

Management of noncardiovascular comorbidities in patients with heart failure with reduced ejection fraction.

Patients with heart failure with reduced ejection fraction often have one or more noncardiovascular comorbidities. The presence of concomitant disease states is associated with worse outcomes, including increased risk of mortality, decreased quality of life, and increased healthcare resource utilization. Additionally, the presence of heart failure with reduced ejection fraction complicates the management of these comorbidities, including varying safety and efficacy of therapies compared to those without heart failure. This article will review the literature on the pharmacologic management of common noncardiovascular comorbidities-including chronic obstructive pulmonary disease, depression, diabetes mellitus, gout, chronic kidney disease, and iron deficiency-in patients with heart failure with reduced ejection fraction, as well as provide recommendations for appropriate treatment selection in this population.

Clinical Outcomes of Perioperative Desensitization in Heart Transplant Recipients.

BACKGROUND: Sensitization remains a barrier to heart transplantation (HT). Perioperative desensitization strategies have been described; however, a paucity of evidence exists to demonstrate efficacy and safety in HT. METHODS: This single-center, retrospective study consisted of adults who received an HT. Perioperative desensitization was initiated if virtual crossmatch or flow-cytometry crossmatch was positive. Therapy consisted of plasmapheresis, intravenous immunoglobulin, and rabbit antithymocyte globulin. Historical controls received standard immunosuppression or induction. The primary endpoint was survival at 12 mo. Secondary endpoints included freedom from acute rejection, cardiac allograft vasculopathy (CAV), and infectious complications. RESULTS: Of the 104 patients included, 48 received no induction, 46 received induction, and 10 underwent perioperative desensitization. No differences were observed in the primary endpoint at 12 mo (90.0% versus 97.9%, P = 0.25 for desensitization versus no-induction; 90.0% versus 100%, P = 0.72 for desensitization versus induction). Rates of acute rejection were lower with induction and desensitization compared with no-induction. There were no significant differences in CAV between the groups. Infectious complications were also similar among the groups (10.0% versus 16.7%, P = 0.62 for desensitization versus no-induction; 10.0% versus 30.4%, P = 0.34 for desensitization versus induction). CONCLUSIONS: This study suggests that a perioperative desensitization strategy triggered by positive virtual crossmatch or flow-cytometry crossmatch allows for successful transplantation of sensitized HT recipients and results in acceptable rates of survival, rejection, CAV, and infection at 12 mo.

The Role of Testosterone in Patients With Heart Failure: A Systematic Review.

The consequences of heart failure (HF) remain high despite treatment advances. Deficiency of the anabolic axes is common in HF and is associated with an increased risk of death and worsening functional status. Exogenous testosterone use has been shown to decrease vascular resistance and improve cardiac output. The objective of this systematic review was to assess the efficacy (mortality, hospitalization, cardiac function, and quality of life) and safety of testosterone in HF patients. The Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) guidelines were followed. Four electronic databases were searched from inception until November 30, 2019. The initial search yielded 1308 articles, and 10 randomized controlled trials with exogenous testosterone in patients with HF were included after exclusion criteria were applied. One study evaluated the impact of testosterone on mortality and HF hospitalization; no difference was observed compared with placebo. In 5 studies, testosterone use was associated with an improvement in walking distance. In 1 of the 2 studies that evaluated functional status, New York Heart Association class was improved. In 2 out of 4 studies, quality of life was improved with therapy. When reported, testosterone use was not associated with an increase in side effects. Overall, testosterone use has not been shown to reduce the risk of death or HF hospitalization, with inconsistent evidence on the impact of therapy on quality of life. Additional trials are needed before testosterone can be recommended. Patients with HF should receive guideline-directed medical therapy with the assurance that patients are receiving maximum tolerated doses.

Pharmacologic Management of Gout in Patients with Cardiovascular Disease and Heart Failure.

Gout is the most common inflammatory arthritis and is often comorbid with cardiovascular disease (CVD). Hyperuricemia and gout are also independent risk factors for cardiovascular events, worsening heart failure (HF), and death. The recommended treatment modalities for gout have important implications for patients with CVD because of varying degrees of cardiovascular and HF benefit and risk. Therefore, it is critical to both manage hyperuricemia with urate-lowering therapy (ULT) and treat acute gout flares while minimizing the risk of adverse cardiovascular events. In this review, the evidence for the safety of pharmacologic treatment of acute and chronic gout in patients with CVD and/or HF is reviewed. In patients with CVD or HF who present with an acute gout flare, colchicine is considered safe and potentially reduces the risk of myocardial infarction. If patients cannot tolerate colchicine, short durations of low-dose glucocorticoids are efficacious and may be safe. Nonsteroidal anti-inflammatory drugs should be avoided in patients with CVD or HF. The use of canakinumab and anakinra for acute gout flares is limited by the high cost, risk of serious infection, and relatively modest clinical benefit. For long-term ULT, allopurinol, and alternatively probenecid, should be considered first-line treatments in patients with CVD or HF given their safety and potential for reducing cardiovascular outcomes. An increased risk of cardiovascular death and HF hospitalization limit the use of febuxostat and pegloticase as ULT in this population. Ultimately, the selection of agents used for acute gout management and long-term ULT should be individualized according to patient and agent cardiovascular risk factors.

An aspirin a day? Clinical utility of aspirin therapy for the primary prevention of cardiovascular disease.

Introduction: Cardiovascular disease remains a leading cause of morbidity and mortality. Since the description of its therapeutic potential, aspirin has been a cornerstone of therapy following vascular events. However, aspirin in the primary prevention setting is controversial and major guideline groups provide inconsistent recommendations. Thus, there is variability in practice as providers are faced with a balance of therapeutic benefit and drug-induced harm. Areas covered: This article provides a critical appraisal of both past and present data for aspirin in the primary prevention setting. PubMed and Cochrane Central Register databases were searched from inception to May 1st, 2019. Expert opinion: The decision to initiate or withdraw aspirin for primary prevention requires an understanding of the equilibrium between efficacy and safety. In adults greater than 70 years of age, low to moderate cardiovascular risk, controlled diabetes, or at high risk of bleeding, initiation of aspirin for primary prevention should generally be avoided. Instead, risk factor modification should be prioritized. The net benefit of aspirin in those at high risk for cardiovascular disease and in those with uncontrolled diabetes is largely unknown. Ultimately, initiation or withdrawal of aspirin therapy must involve discussion of the patient's wishes and treatment expectations.

Alemtuzumab Induction Versus Conventional Immunosuppression in Heart Transplant Recipients.

The use of alemtuzumab for induction therapy in orthotopic heart transplantation remains controversial, despite its observed benefits in other transplant populations. This study aimed to evaluate whether alemtuzumab conferred a lower risk of rejection while reducing toxicities commonly attributed to standard immunosuppression in orthotopic heart transplantation. We included adult patients who underwent orthotopic heart transplantation and received induction therapy with alemtuzumab (n = 26) or standard immunosuppression (n = 26). The primary end point was freedom from grade ≥2 rejection at 12 months. Baseline characteristics were similar between the groups with the exception of poorer renal function in the alemtuzumab group (P < .05). The primary end point of freedom from grade ≥2 rejection at 12 months was not different between alemtuzumab and standard therapy (76.9% vs 96.2%, P = .077), likely due to similarities in the rates of antibody-mediated rejection in the 2 groups. However, grade ≥2 acute cellular rejection was considerably lower with alemtuzumab (0% vs 19.2%, P = .02), as was acute cellular rejection of any severity (50% vs 7.7%, P = .004). Deterioration in renal function was significantly greater among patients receiving standard therapy as evidenced by decreases in glomerular filtration rate (-25.6 vs -9.2 mL/min, P = .032). No differences in hematologic or infectious complications were observed. In conclusion, alemtuzumab reduced several important rejection-related outcomes while ameliorating the toxicities associated with standard immunosuppression therapy, making it a promising agent for induction in orthotopic heart transplantation.

Antihyperglycemic Medications and Impact on Cardiovascular Outcomes: A Review of Current Evidence.

Patients with type 2 diabetes mellitus (DM) are known to be at an increased risk for macrovascular complications, and cardiovascular disease (CVD) is one of the greatest drivers of morbidity and mortality in this patient population. Over the past decade, the number of treatment options for type 2 DM has increased. In 2008, the United States Food and Drug Administration mandated an evaluation of cardiovascular (CV) outcomes associated with antihyperglycemic agents. Since that time, the CV risk-benefit profile of many antihyperglycemic treatment modalities have been evaluated; however, results have remained inconsistent. This article will review the literature on the use of pharmacologic therapies in patients with type 2 DM and associated CVD risk, as well as provide recommendations for appropriate treatment selection in this population. Current evidence has demonstrated CV benefits with metformin, select glucagon-like peptide-1 receptor agonists (liraglutide), and sodium-glucose co-transporter 2 inhibitors (canagliflozin and empagliflozin).

Ombitasvir/paritaprevir/ritonavir and dasabuvir tablets for hepatitis C virus genotype 1 infection.

OBJECTIVE: To review the data with ombitasvir/paritaprevir/ritonavir and dasabuvir for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection. DATA SOURCES: Phase I, II, and III trials and review articles were identified through MEDLINE (1996-January 2015) and PubMed (1996-January 2015), conference abstracts, and US national clinical trials registry, using the keywords NS3/4A protease inhibitor, NS5A inhibitor, NS5B polymerase inhibitor, ABT-450, ABT-267, ABT-333, paritaprevir, ombitasvir, and dasabuvir. STUDY SELECTION AND DATA EXTRACTION: Preclinical, phase I, II, and III studies describing pharmacology, pharmacokinetics, efficacy, safety, and tolerability were identified. DATA SYNTHESIS: Noncirrhotic patients with HCV genotype 1b experienced sustained virological response 12 weeks after completion of therapy (SVR12) rates of 96% to 100% when ombitasvir/paritaprevir/ritonavir and dasabuvir were administered for 12 weeks, regardless of inclusion of ribavirin. SVR12 rates of 95% to 97% were seen in noncirrhotic patients with HCV genotype 1a infection who received ombitasvir/paritaprevir/ritonavir and dasabuvir with ribavirin for 12 weeks. Patients with Child-Pugh Class A cirrhosis also experienced high SVR12 rates (91.8%) when ombitasvir/paritaprevir/ritonavir and dasabuvir were administered with ribavirin for 12 weeks. Cirrhotic patients with HCV genotype 1a and a history of prior null response to peginterferon/ribavirin have higher SVR12 rates when ombitasvir/paritaprevir/ritonavir and dasabuvir and ribavirin are administered for 24 instead of 12 weeks (94.2% vs 88.6%). Adverse events are typically mild, most commonly consisting of fatigue, headache, nausea, and diarrhea. CONCLUSION: The regimen consisting of ombitasvir/paritaprevir/ritonavir and dasabuvir is highly efficacious in the treatment of HCV genotype 1 infection, with minimal adverse events. It is expected to play an important role in the armamentarium of novel agents that have a high chance of curing HCV infection.