A Practical Guide to Understanding and Treating Peripheral Artery Disease.

ABSTRACT: Peripheral arterial disease (PAD) is the third leading cause of atherosclerotic morbidity after coronary heart disease and stroke yet is widely underdiagnosed and undertreated. Treatment of risk factors such as diabetes and cigarette smoking can benefit patients with PAD. Patients should have adequate blood pressure and lipid control to decrease clinical manifestations and symptoms of PAD. Use of antithrombotic medications should be individualized to the patient depending on the presence of symptoms, revascularization, and comorbidities. All patient care providers, including physicians, pharmacists, nurse practitioners, and physician assistants, should incorporate PAD screening in their at-risk patients to improve access for appropriate earlier diagnosis, initiation of guideline directed therapy, and risk factor modification to reduce both major adverse CV and limb outcomes. The purpose of this narrative review is to provide an overview of PAD and summarize clinical trial evidence and guideline recommendations for screening and treatment to increase awareness among health care providers to ultimately have a positive impact on patient care.

Long-Term Retention of Advanced Cardiovascular Life Support Knowledge and Confidence in Doctor of Pharmacy Students.

OBJECTIVE: This study aimed to evaluate the impact of American Heart Association (AHA) advanced cardiovascular life support (ACLS) education and training on long-term retention of ACLS knowledge and confidence in Doctor of Pharmacy (PharmD) students. METHODS: This multicenter study included PharmD students who received ACLS training through different means: 1-hour didactic lecture (didactic), 1-hour didactic lecture with 2-hour skills practice (didactic + skills), and comprehensive AHA ACLS certification through an elective course (elective-certification). Students completed a survey before training, immediately after training, and at least 6-12 months after training to assess demographics and ACLS confidence and knowledge. The primary outcome was a passing score, defined as ≥ 84% on the long-term knowledge assessment. Secondary outcomes included overall knowledge score and perceived confidence, assessed using the Dreyfus model. RESULTS: The long-term assessment was completed by 160 students in the didactic group, 66 in the didactic + skills group, and 62 in the elective-certification group. Six (4%), 8 (12%), and 14 (23%) received a passing score on the long-term knowledge assessment in the didactic, didactic + skills, and elective-certification groups, respectively. The median (IQR) scores on the long-term knowledge assessment were 50% (40-60), 60% (50-70), and 65% (40-80) in the 3 groups. On the long-term assessment, confidence was higher in the elective-certification group, demonstrated by more self-ratings of competent, proficient, and expert, and fewer self-ratings of novice and advanced beginner. CONCLUSION: Long-term retention of ACLS knowledge was low in all groups, but was higher in students who received AHA ACLS certification through an ACLS elective course.

Inpatient Initiation of Sacubitril/Valsartan.

OBJECTIVE: Discuss the literature and describe strategies to overcome barriers of inpatient initiation of sacubitril/valsartan in patients with heart failure with reduced ejection fraction (HFrEF). DATA SOURCES: A PubMed, EMBASE, and Google Scholar literature search (January 2014 to June 2020) limited to English language articles was conducted with the following terms: sacubitril/valsartan, initiation, inpatient, hospitalized, B-type natriuretic peptide (BNP), N-terminal pro-B-type natriuretic peptide (NT-proBNP), diuretic, cost, and cost-effectiveness. STUDY SELECTION AND DATA EXTRACTION: Included articles described inpatient initiation of sacubitril/valsartan or described its impact on BNP, NT-proBNP, diuretic dosing, or cost of care. DATA SYNTHESIS: A total of 20 studies were identified based on included search terms. CONCLUSIONS: Sacubitril/valsartan should be considered for hemodynamically stable patients with HFrEF (New York Heart Association class II or III), potassium <5.2 mmol/L, without a history of angioedema, and after a 36-hour washout from angiotensin-converting enzyme (ACE) inhibitor or aliskiren, if applicable. An appropriate dose can be determined based on the patient's previous ACE inhibitor or angiotensin receptor blocker dose and/or blood pressure along with patient-specific factors. To overcome barriers of use, the following are recommended: NT-proBNP or BNP with establishment of a new baseline 1 month after initiation may be used for prognosis or diagnosis; careful monitoring of diuretic requirements; utilization of multiple strategies to overcome cost barriers; and use of interdisciplinary care.

The Fall Risk with Alpha blockers Given InitiaL dose or Elderly status (FRAGILE) Study.

Background: α-1 adrenergic antagonists are commonly prescribed, but there is question regarding their safety in patients at increased fall risk. Objective: The purpose of the FRAGILE study was to determine the risk for developing adverse drug events (ADEs) in veterans prescribed α-1 blockers. Methods: A single-center, retrospective, observational cohort analysis was conducted of veterans newly initiated on α-1 antagonists. Veterans were categorized into at-risk (patients who met at least 1 of 2 criteria: age 65 or older or high initial dose of α blockade) or control (veterans without either risk factor) groups. The primary outcome was the composite all-cause ADEs, including hospitalizations or emergency department (ED) visits. Secondary outcomes included number of fall-related ADEs and medication discontinuation rates with follow-up for 12 months. Results: A total of 300 veterans were evaluated. There was no significant difference in the composite outcome of all-cause ED visits between at-risk (n = 169) versus control (n = 131) groups (0.81 vs 1.17, P = 0.09) or all-cause hospitalizations (0.28 vs 0.39, P = 0.25). Seventy-three veterans in the at-risk group experienced an all-cause ADE versus 64 in the control group (P = 0.36). No significant differences in secondary outcomes were found. Fall-related side effects occurred in 8% of the total cohort. Conclusion and Relevance: Rates of all-cause or fall-related ADEs were not significantly different. An 8% discontinuation rate resulting from fall-related ADEs and high rates of coadministered medications that could increase fall risk. Pharmacists can play a key role in optimizing α-1 blocker administration.

An Underappreciated and Prolonged Drug Interaction Leads to Ineffective Anticoagulation.

A poorly understood significant drug-drug interaction compounded by ineffective communication among providers at times of care transition most likely contributed to multiple thromboembolic events in an 81-year-old patient. Increased awareness of drug interactions with direct oral anticoagulants (DOACs), as well as improved communication among inpatient and outpatient providers at the time of discharge is essential in maximizing efficacy and safety outcomes in patients requiring chronic anticoagulation. When rifampin is coadministered with apixaban, a reduction in apixaban exposure results in decreased efficacy and increased risk for thromboembolic events. The delayed effect of rifampin deinduction should be considered with regard to potential drug interactions even after its discontinuation. Equally as important, patients with multiple comorbidities and polypharmacy are at significant risk from adverse drug events during the transition from hospital to home. All efforts to improve continuity of care at times of transition, including medication reconciliation, prompt delivery of discharge summaries to outpatient providers, effective communication among providers, and patient education are components of a best practices model that has the potential to lower costs, improve medication adherence, decrease adverse drug events, and reduce hospital readmissions.

A New Option for Reversing the Anticoagulant Effect of Factor Xa Inhibitors: Andexanet Alfa (ANDEXXA).

The use of direct oral anticoagulants over traditional warfarin has increased in the United States over the past 10 years because of advantages such as ease of use, predictable pharmacokinetic response, and safety. In 2015, the U.S. Food and Drug Administration approved idarucizumab (Praxbind) for the reversal of the direct thrombin inhibitor dabigatran, but no reversal agent has been available for oral factor Xa (FXa) inhibitors until recently. Andexanet alfa was approved in May 2018, under the brand name ANDEXXA, for the reversal of 2 of FXa inhibitors, apixaban and rivaroxaban, when life-threatening or uncontrolled bleeding occurs. This accelerated approval was based on change in anti-FXa activity from baseline that indicated a reversal of the anticoagulant effect. Any expanded Food and Drug Administration indication will be contingent on results demonstrating improved hemostasis and efficacy for reversing other FXa inhibitors.

Effect of post-primary percutaneous coronary intervention bivalirudin infusion on net adverse clinical events and mortality: A comprehensive pairwise and network meta-analysis of randomized controlled trials.

OBJECTIVE: To compare the efficacies of various post-percutaneous coronary intervenetion (PCI) bivalirudin doses on net adverse clinical events (NACEs) and mortality. BACKGROUND: In primary PCI, lower risk of bleeding with bivalirudin (vs. unfractionated heparin [UFH]) is counterbalanced by an increased risk of acute stent thrombosis (ST). Several randomized clinical trials (RCTs) and a recent meta-analysis suggest that acute ST risk may be eliminated without compromising the bleeding benefit, but only if the full dose, not a low dose, of bivalirudin is continued post-PCI. However, it is not known whether this improved risk leads to lower rates of NACEs and mortality. METHODS: Scientific databases and Web sites were searched for RCTs. Trials were included if study patients were undergoing primary PCI for acute ST-segment elevation myocardial infarction and were randomly assigned to bivalirudin or UFH treatment. The bivalirudin arm was divided based on post-PCI bivalirudin dosage: The Biv-Full group received 1.75 mg/kg/h, the Biv-Low group, 0.25 mg/kg/h, and the Biv-No group, none. RESULTS: Six RCTs involving 16,842 patients were found. In pairwise meta-analysis, bivalirudin improved 30-day all-cause mortality by 35% and cardiac mortality by 32%, but did not yield a NACE rate better than that achieved with UFH. Subgroup analysis showed the Biv-Full group had a 46% lower NACE rate and 47% lower all-cause mortality than UFH. These effects were not seen in the other two groups. Network meta-analysis yielded similar results. At treatment ranking, the Biv-Full group yielded the best treatment efficacy. CONCLUSIONS: In primary PCI, full-dose bivalirudin infusion for 3-4 hr after PCI appeared to improve NACE rates compared to UFH. It also seemed to be the most effective strategy for improving cardiac mortality and all-cause mortality. © 2016 Wiley Periodicals, Inc.

Reversal Agents for Direct Oral Anticoagulants: Understanding New and Upcoming Options.

Direct oral anticoagulants (DOACs), originally developed as an alternative for vitamin K antagonists, are shifting the landscape of antithrombotic therapy. DOACs such as dabigatran, rivaroxaban, apixaban, and edoxaban offer enhancements in safety, convenience, and efficacy compared with warfarin. However, as choices for oral anticoagulation therapy have increased, so has the need for effectual antidotes before urgent surgical procedures and for the reversal of serious adverse events caused by DOACs. To date, one antidote has been FDA approved in the United States for the reversal of dabigatran, and two antidotes are undergoing phase 2and 3clinical trials. This review will summarize currently available and developing data for DOAC antidotes: idarucizumab, exanet alfa, and ciraparantag.

Effect of Post-Primary Percutaneous Coronary Intervention Bivalirudin Infusion on Acute Stent Thrombosis: Meta-Analysis of Randomized Controlled Trials.

OBJECTIVES: The aim of this study was to evaluate the efficacy of various doses of post-primary percutaneous coronary intervention (PCI) bivalirudin infusion to prevent acute stent thrombosis (AST). BACKGROUND: In several recent randomized controlled trials, bivalirudin infusion was continued post-PCI as either a full PCI dose (Biv-Full) or a reduced dose (Biv-Low) to reduce the risk for AST. The results of these trials varied, so the authors performed a meta-analysis of RCTs to determine whether the risk for AST is dose dependent. METHODS: Scientific databases and Web sites were searched for RCTs. A traditional meta-analysis was performed using moderator analyses and network meta-analysis using mixed-treatment comparison models to compare the efficacy of various bivalirudin doses in reducing AST. RESULTS: Data from 5 trials including 16,294 patients were analyzed. Compared with heparin, bivalirudin increased AST risk 2-fold, but this was ameliorated by continuing Biv-Full (risk ratio: 0.90, 95% confidence interval: 0.32 to 2.54; p = 0.852). This effect was not seen with Biv-Low. Similarly, in mixed-treatment models, no difference in AST rate was found between heparin and Biv-Full (odds ratio: 0.97; 95% confidence interval: 0.36 to 2.21). After 30 days, bivalirudin decreased the risk for major bleeding by 47% compared with heparin; this benefit persisted even with continued Biv-Full post-PCI (risk ratio: 0.29; 95% confidence interval: 0.16 to 0.53; p < 0.001). CONCLUSIONS: Although bivalirudin is associated with a greater risk for AST than heparin post-primary PCI, this limitation may be mitigated by continuing Biv-Full (not Biv-Low) 3 to 4 h post-operatively. The decrease in bleeding risk with bivalirudin compared with heparin is not compromised by this strategy.

An updated comprehensive meta-analysis of bivalirudin vs heparin use in primary percutaneous coronary intervention.

BACKGROUND: Despite several randomized controlled trials and meta-analyses, the ideal anticoagulant for patients undergoing primary percutaneous coronary intervention (PCI) remains controversial. We performed an updated meta-analysis including recently reported randomized clinical trials that compare bivalirudin and heparin with or without provisional administration of a glycoprotein IIb/IIIa inhibitor (GPI) for primary PCI. METHODS AND RESULTS: Scientific databases and Web sites were searched for randomized clinical trials. Data from 6 trials involving 14,095 patients were included. The pooled risk ratios (RRs) were calculated using random-effects models. Moderator analyses examined the impact of routine use of GPI, radial access, and P2Y12 inhibitors on safety outcomes. At 30 days, patients receiving bivalirudin had rates of major adverse cardiac events similar to those receiving heparin with or without provisional GPI (RR 1.02, 95% CI 0.87-1.19, P = .800), myocardial infarction (RR 1.41, 95% CI 0.94-2.11, P = .089), target vessel revascularization (RR 1.37, 95% CI 0.91-2.04, P = .122), and net adverse clinical events (RR 0.81, 95% CI 0.64-1.01, P = .069). However, bivalirudin use decreased the risk of all-cause mortality (RR 0.81, 95% CI 0.67-0.99, P = .041) and cardiac mortality (RR 0.68, 95% CI 0.51-0.91, P = .009) at 30 days, There were higher rates of acute stent thrombosis (RR 3.31, 95% CI 1.79-6.10, P < .001) in patients receiving bivalirudin. Bivalirudin use also decreased the risk of major bleeding at 30 days by 37% (RR 0.63, 95% CI 0.44-0.90, P = .012), but bleeding risk varied depending on routine GPI use with heparin (RR 0.44, 95% CI 0.23-0.81, P = .009) vs bailout (RR 0.73, 95% CI 0.42-1.25, P = .252), predominantly radial access (RR 0.54, 95% CI 0.25-1.15, P = .114) vs non-radial access (RR 0.60, 95% CI 0.36-0.99, P = .049), and second-generation P2Y12 inhibitor use with bivalirudin (RR 0.70, 95% CI 0.40-1.24, P = .226) vs clopidogrel use (RR 0.39, 95% CI 0.18-0.85, P = .018). CONCLUSIONS: In primary PCI, relative to heparin, bivalirudin reduces the risk for all-cause mortality, cardiac mortality, and major bleeding but yields similar rates of major adverse cardiac event and net adverse clinical event at 30 days. However, the benefit of a reduction in bleeding with bivalirudin appears to be modulated by the concurrent administration of second-generation P2Y12 inhibitors with bivalirudin, using radial access, and avoiding routine GPI use with heparin.

Clinical efficacy and safety of cilostazol: a critical review of the literature.

Cilostazol is a unique antiplatelet agent that has been commercially available for over two decades. As a phosphodiesterase III inhibitor, it reversibly inhibits platelet aggregation yet also possesses vasodilatory and antiproliferative properties. It has been widely studied in a variety of disease states, including peripheral arterial disease, cerebrovascular disease, and coronary artery disease with percutaneous coronary intervention. Overall, cilostazol appears to be a promising agent in the management of these disease states with a bleeding profile comparable to placebo; even when combined with other antiplatelet agents, cilostazol does not appear to increase the rate of bleeding. Despite the possible benefit of cilostazol, its use is limited by tolerability as some patients often report drug discontinuation due to headache, diarrhea, dizziness, or increased heart rate. To date, it has been predominantly studied in the Asian population, making it difficult to extrapolate these results to a more diverse patient population. This paper discusses the evolving role of cilostazol in the treatment of vascular diseases.

Annual influenza vaccination: offering protection beyond infection.

Cardiovascular disease (CVD), the leading cause of death in the world, is largely preventable. An increasing amount of evidence suggests that annual vaccination with inactivated influenza vaccine reduces morbidity and mortality associated with CVD; however, immunization rates in patients with CVD fall consistently below the goals established by Healthy People 2020. This review outlines the importance of vaccination and summarizes the available literature on the role of seasonal influenza vaccination and the incidence of coronary artery disease and stroke.

Use of cilostazol in percutaneous coronary interventions.

OBJECTIVE: To evaluate the addition of cilostazol to standard dual antiplatelet therapy (DAT) with aspirin and clopidogrel in patients receiving coronary stenting. DATA SOURCES: Relevant information was identified through a search of MEDLINE (1966-November 2011), International Pharmaceutical Abstracts (1960-2011), and Cochrane Databases (publications archived until November 2011) using the terms cilostazol, percutaneous coronary intervention, triple therapy, and antiplatelet agents. STUDY SELECTION AND DATA EXTRACTION: English-language prospective and retrospective studies, including registry data in adults, were eligible for inclusion if triple therapy with cilostazol was compared with DAT with aspirin and clopidogrel in patients undergoing percutaneous coronary intervention (PCI) with stenting. Article bibliographies were also reviewed. DATA SYNTHESIS: Cilostazol uniquely possesses antiproliferative properties in addition to its antiplatelet effects. Several prospective and retrospective clinical trials evaluated it as a third agent in standard antiplatelet regimens after PCI with both bare metal and drug-eluting stents. Both angiographic and clinical outcomes, including major adverse cardiac events (MACEs), have been improved with the addition of cilostazol to DAT in most trials, without increasing bleeding risk. Higher-risk patients, such as elderly individuals and patients with diabetes, long lesions, or small vessels, seem to benefit the most from triple therapy. Patients who are poor responders to clopidogrel also appear to benefit from the addition of cilostazol by improving platelet reactivity with standard DAT. CONCLUSIONS: Triple therapy with cilostazol has been shown to reduce MACEs by providing increased inhibition of platelet aggregation and reducing the rates of in-stent thrombosis compared to DAT without increasing the risk of bleeding complications. Further studies are needed to identify proper patient selection based on risk factors for the addition of cilostazol. Additionally, studies comparing cilostazol with newer antiplatelet therapies, such as prasugrel and ticagrelor, are needed.

Key articles of dietary interventions that influence cardiovascular mortality.

Lifestyle modifications, particularly diet, are a key component to the reduction of cardiovascular events. Diets high in carbohydrates and saturated fat have been shown to negatively affect blood cholesterol, thereby increasing the risk for cardiovascular disease (CVD). Dietary interventions that emphasize the consumption of whole grains, fruits, and vegetables have been shown to be successful in reducing cardiovascular risk. Clinical pharmacist practitioners need to be knowledgeable regarding lifestyle modifications, specifically dietary issues, to develop a comprehensive, effective, and evidence-based plan for patients who are either at risk for or who have established CVD. Numerous studies have been published over the past few years with regard to the rapidly growing field of dietary interventions that influence cardiovascular risk, and the amount of literature can be overwhelming. Thus we chose to focus our review on articles that assess changes in dietary patterns that affect overall mortality risk from CVD. As such, literature describing the impact of dietary factors that influence weight, lipid changes, or other risk factors alone were not included in this review. A group of practitioners with expertise and interest in CVD were involved in the compilation of this article.

Assessment of sotalol prescribing in a community hospital: opportunities for clinical pharmacist involvement.

OBJECTIVE: Due to risk of serious adverse drug events (ADEs) sotalol use is limited in renal insufficiency and heart failure. To reduce potential life-threatening ADEs, medication safety initiatives that ensure appropriate dosing of sotalol are necessary. Pharmacist-managed renal dosing assessment programmes ensure appropriate dosing of renally eliminated medications. A prospective medication safety evaluation was conducted to assess the need to include sotalol in an existing renal dosing assessment programme as well as the impact of clinical pharmacist assessment on sotalol prescribing. METHODS: Patients in a 736-bed community hospital, receiving sotalol during a 6-week period, were prospectively evaluated. Information was collected on indication, dosing, concomitant disease states and medications, renal function, QTc length, symptoms of toxicity and readmissions. Pharmacist recommendations were made when necessary and were followed to determine acceptance rate and patient outcomes. KEY FINDINGS: Thirty-six patients were prescribed sotalol for atrial tachyarrhythmias. Thirty-two (89%) were dosed inappropriately with respect to renal function. Twenty (56%) had left-ventricular dysfunction as defined by an ejection fraction of ≤ 40%. At time of initial assessment, 15 (42%) were exhibiting signs of potential sotalol toxicity. Pharmacists provided recommendations regarding discontinuation or dosage adjustment on 32 patients with a 38% full and a 12% partial acceptance rate. All-cause readmission rates for patients receiving appropriate therapy, including those after pharmacist recommendations were accepted (Group A; n=16), were compared to those remaining on inappropriate therapy (Group B; n=20). Readmission rates within 6 months differed between groups (31% for Group A, 55% for Group B; P=0.095, odds ratio 3.7). CONCLUSION: This medication safety evaluation suggests the need for pharmacist assessment in patients receiving sotalol. Dosage adjustment or avoidance in patients with renal insufficiency, heart failure and other relative contraindications is often necessary to avoid toxicity. Sotalol was inappropriately prescribed in the majority of patients secondary to renal insufficiency. Based on this evaluation, it was recommended to add sotalol to the institution's pharmacist-managed renal dosing adjustment programme. Ensuring clinical pharmacist assessment when sotalol is prescribed can help reduce potential life-threatening ADEs and hospital readmissions.

Basic life support and cardiopulmonary resuscitation training for pharmacy students and the community by a pharmacy student committee.

OBJECTIVE: To create a self-sufficient, innovative method for providing cardiopulmonary resuscitation (CPR) education within a college of pharmacy using a student-driven committee, and disseminating CPR education into the community through a service learning experience. DESIGN: A CPR committee comprised of doctor of pharmacy (PharmD) students at the University of Tennessee College of Pharmacy provided CPR certification to all pharmacy students. The committee developed a service learning project by providing CPR training courses in the community. Participants in the course were required to complete an evaluation form at the conclusion of each training course. ASSESSMENT: The CPR committee successfully certified more than 1,950 PharmD students and 240 community members from 1996 to 2009. Evaluations completed by participants were favorable, with 99% of all respondents (n = 351) rating the training course as either "excellent" or "good" in each of the categories evaluated. CONCLUSION: A PharmD student-directed committee successfully provided CPR training to other students and community members as a service learning experience.

Job sharing for women pharmacists in academia.

The pharmacist shortage, increasing numbers of female pharmacy graduates, more pharmacy schools requiring faculty members, and a lower percentage of female faculty in academia are reasons to develop unique arrangements for female academic pharmacists who wish to work part-time. Job sharing is an example of a flexible alternative work arrangement that can be successful for academic pharmacists who wish to continue in a part-time capacity. Such partnerships have worked for other professionals but have not been widely adopted in pharmacy academia. Job sharing can benefit the employer through retention of experienced employees who collectively offer a wider range of skills than a single employee. Benefits to the employee include balanced work and family lives with the ability to maintain their knowledge and skills by remaining in the workforce. We discuss the additional benefits of job-sharing as well as our experience in a non-tenure track job-sharing position at the University of Tennessee College of Pharmacy.