RESUMEN

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.

Asunto(s)

RESUMEN

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.

Asunto(s)

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

BACKGROUND: Vitamin D status may influence heart failure (HF) patient outcomes by affecting b-type natriuretic peptide (BNP), parathyroid hormone (PTH), and enhancing cardiac contractility. Vitamin D deficiency is associated with morbidity and mortality in HF patients. The objective of this study was to determine if vitamin D3 at a comparatively high dose would replete 25-hydroxyvitamin D (25(OH)D) stores, improve BNP, PTH, cardiopulmonary function, reduce inflammatory markers, and improve quality of life (QOL) in HF patients. METHODS: This was a 6 month, parallel group, double-blind, placebo-controlled, single clinic center, randomized trial of supplemental vitamin D3 using a dose of 10,000 IU daily or placebo in 40 vitamin D deficient or insufficient (25(OH)D level ≤ 32 ng/ml) patients with stable New York Heart Association Class II-III HF in a specialty cardiology clinic. All variables were measured at baseline and 6 months. Values between the two treatment groups were assessed using Student's t-test or Mann-Whitney Test. Univariate analysis of covariance was conducted to adjust for variance in baseline 25(OH)D. RESULTS: All results were adjusted for baseline 25(OH)D. The change in BNP from baseline was ∆ +30 ± 950 pg/ml for treatment vs. placebo ∆ +400 ± 1900 pg/ml, p = 0.003. 25(OH)D serum levels rose by 49 ± 32 ng/ml in the treatment group vs 4 ± 10 ng/ml in the placebo group, p < 0.001. PTH and exercise chronotropic response index improved in the treatment group vs placebo group, respectively, but both were attenuated by adjustment ((∆-20 ± 20 pg/ml vs ∆ + 7 ± 53 pg/ml respectively (p = 0.01, adjusted p = 0.07)) and (∆ + 0.13 ± 0.26 vs. ∆-0.03 ± 02.9 respectively, p < 0.01, adjusted p = 0.17)). Other measured cardiopulmonary parameters remained unchanged. High sensitivity C-reactive protein (hsCRP) remained unchanged for women, but improved for men (∆-2 ± 4 treatment versus ∆2 ± 5 mg/L placebo, p = 0.05). QOL scores, including composite overall and clinical summary scores significantly improved in treatment compared to placebo (∆ + 10 ± 15 versus -6 ± 15, p < 0.01 and ∆ + 8 ± 14 versus -8 ± 18, p = 0.01, respectively). CONCLUSIONS: Repletion of 25(OH)D may improve QOL in HF patients and may help to normalize BNP, PTH, and hsCRP. TRIAL REGISTRATION: Clinicaltrials.gov, Trial Registration Number: NCT01636570 , First registered 3 July 2012.

Asunto(s)

RESUMEN

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.

Asunto(s)

RESUMEN

OBJECTIVE: The objectives of this study were to develop a novel training model for using mass-casualty incident (MCI) scenarios that trained hospital and prehospital staff together using Microsoft Visio, images from Google Earth and icons representing first responders, equipment resources, local hospital emergency department bed capacity, and trauma victims. The authors also tested participants' knowledge in the areas of communications, incident command systems (ICS), and triage. METHODS: Participants attended Managing Multiple-Casualty Incidents (MCIs), a one-day training which offered pre- and post-tests, two one-hour functional exercises, and four distinct, one-hour didactic instructional periods. Two MCI functional exercises were conducted. The one-hour trainings focused on communications, National Incident Management Systems/Incident Command Systems (NIMS/ICS) and professional roles and responsibilities in NIMS and triage. The trainings were offered throughout communities in western Montana. First response resource inventories and general manpower statistics for fire, police, Emergency Medical Services (EMS), and emergency department hospital bed capacity were determined prior to MCI scenario construction. A test was given prior to and after the training activities. RESULTS: A total of 175 firefighters, EMS, law enforcement, hospital personnel or other first-responders completed the pre- and post-test. Firefighters produced higher baseline scores than all other disciplines during pre-test analysis. At the end of the training all disciplines demonstrated significantly higher scores on the post-test when compared with their respective baseline averages. Improvements in post-test scores were noted for participants from all disciplines and in all didactic areas: communications, NIMS/ICS, and triage. CONCLUSIONS: Mass-casualty incidents offer significant challenges for prehospital and emergency room workers. Fire, Police and EMS personnel must secure the scene, establish communications, define individuals' roles and responsibilities, allocate resources, triage patients, and assign transport priorities. After emergency department notification and in advance of arrival, emergency department personnel must assess available physical resources and availability and type of manpower, all while managing patients already under their care. Mass-casualty incident trainings should strengthen the key, individual elements essential to well-coordinated response such as communications, incident management system and triage. The practice scenarios should be matched to the specific resources of the community. The authors also believe that these trainings should be provided with all disciplines represented to eliminate training "silos," to allow for discussion of overlapping jurisdictional or organizational responsibilities, and to facilitate team building.

Asunto(s)

RESUMEN

PURPOSE The results of a survey assessing the practice settings, clinical activities, and reimbursement experiences of pharmacists with advanced-practice designations are reported. METHODS A questionnaire was sent to all certified Pharmacist Clinicians in New Mexico and all Clinical Pharmacist Practitioners in North Carolina (a total of 189 pharmacists at the time of the survey in late 2008) to elicit information on practice settings, billing and reimbursement methods, collaborative drug therapy management (CDTM) protocols, and other issues. RESULTS Of the 189 targeted pharmacists, 64 (34%) responded to the survey. On average, the reported interval from pharmacist licensure to certification as an advanced practitioner was 11 years. The majority of survey participants were practicing in community or institutional settings, most often hospital clinics or physician offices. About two thirds of the respondents indicated that their employer handled the billing of their services using standard evaluation and management codes, with estimated total monthly billings averaging $6500. At the time of the survey, about 80% of the respondents were engaged in a CDTM protocol. The survey results suggest that pharmacists with advanced-practice designations are perceived favorably by patients and physicians and their services are in high demand, but more than one third of respondents indicated a need to justify their advanced-practice positions to administrators. CONCLUSION Pharmacists with advanced-practice designations are providing clinical services in various settings under collaborative practice arrangements that include prescribing privileges. Despite growing patient and physician acceptance, reimbursement challenges continue to be a barrier to wider use of CDTM programs.

Asunto(s)

RESUMEN

Minimally invasive applications of thermal and mechanical energy to selective areas of the human anatomy have led to significant advances in treatment of and recovery from typical surgical interventions. Image-guided focused ultrasound allows energy to be deposited deep into the tissue, completely noninvasively. There has long been interest in using this focal energy delivery to block nerve conduction for pain control and local anesthesia. In this study, we have performed an in vitro study to further extend our knowledge of this potential clinical application. The sciatic nerves from the bullfrog (Rana catesbeiana) were subjected to focused ultrasound (at frequencies of 0.661 MHz and 1.986 MHz) and to heated Ringer's solution. The nerve action potential was shown to decrease in the experiments and correlated with temperature elevation measured in the nerve. The action potential recovered either completely, partially or not at all, depending on the parameters of the ultrasound exposure. The reduction of the baseline nerve temperature by circulating cooling fluid through the sonication chamber did not prevent the collapse of the nerve action potential; but higher power was required to induce the same endpoint as without cooling. These results indicate that a thermal mechanism of focused ultrasound can be used to block nerve conduction, either temporarily or permanently.

Asunto(s)

RESUMEN

OBJECTIVE: To report 2 cases of worsened heart failure (HF) after the introduction of venlafaxine or duloxetine therapy in patients with previously stable disease. CASE SUMMARIES: Two patients, a 39-year-old female and a 68-year-old male, both diagnosed with HF of left ventricular systolic dysfunction, had worsening symptoms in the presence of the serotonin and norepinephrine reuptake inhibitors (SNRIs) venlafaxine 75 mg twice daily and/or duloxetine 30-60 mg/day. Both patients developed tachycardia, which remitted after the discontinuation of these agents. The woman was rechallenged with duloxetine 60 mg daily after her HF worsened with venlafaxine, only to have the tachycardia and HF symptoms return. Other iatrogenic causes and metabolic disturbances (eg, anemia) were ruled out. DISCUSSION: Increased levels of norepinephrine secondary to reuptake inhibition may be potentially deleterious in patients with chronic HF of left ventricular dysfunction owing to the "progressive HF model" and neurohormonal compensatory responses. Use of the Naranjo probability scale showed a probable relationship between venlafaxine/duloxetine use and these adverse outcomes. Venlafaxine and duloxetine were discontinued. CONCLUSIONS: Use of drugs that increase serum norepinephrine levels, such as the SNRIs, may be potentially deleterious in individuals with unstable or advanced HF. These medications should be avoided or used with caution and monitored regularly in this patient population.

Asunto(s)

RESUMEN

OBJECTIVE: To review and discuss key aspects of the drug therapy recommendations in the American College of Cardiology (ACC)/American Heart Association (AHA) 2005 Guideline Update for the Diagnosis and Management of Chronic Heart Failure (HF) in the Adult. DATA SOURCES: Data were obtained from the ACC/AHA 2005 Guideline Update for Chronic HF. English-language clinical trials, observational studies, and pertinent review articles evaluating the pharmacotherapy of chronic HF were identified, based on MEDLINE searches through January 2006. STUDY SELECTION: Articles presenting information that impacts the evidence base for recommendations regarding the use of various drug therapies in patients with chronic HF were evaluated. DATA SYNTHESIS: The ACC/AHA 2005 Guideline Update for HF provides revised, evidence-based recommendations for the treatment of chronic HF. The new guidelines are based on a staging system that recognizes both the development and progression of HF. Recommendations are provided for 2 stages of patients (A and B) who do not yet have clinical HF but are clearly at risk and 2 stages (C and D) that include patients with symptomatic HF. The guidelines continue to emphasize the important role of neurohormonal blockade with angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-adrenergic blockers, and aldosterone antagonists. Based on recent trials, updated recommendations address the roles of combination therapy and the selective addition of hydralazine and isosorbide dinitrate. Along with specific drug recommendations, information on the practical use of various drugs is provided. Although the guidelines primarily focus on HF due to systolic dysfunction, general recommendations are also provided for patients with preserved systolic function. CONCLUSIONS: The ACC/AHA 2005 Guideline Update provides evidence-based recommendations for healthcare professionals involved in the care of adults with chronic HF. Recent clinical trial findings have further clarified the evolving role of neurohormonal-blocking drugs in the prevention and treatment of HF.

Asunto(s)

RESUMEN

A 49-year-old man electively chose to undergo a trial of intravenous chemotherapy with 5-fluorouracil (5-FU) for his inherited punctate palmoplantar keratoderma (PPK). His father also had this skin disorder, which coincidentally cleared after 2 courses of chemotherapy consisting of 5-FU and cisplatin to treat his lung cancer, prompting the patient to undergo this trial of therapy. After the patient's first course of a 5-day continuous infusion (CI) of 5-FU (1000 mg/m2 per day), the lesions on his hands and feet regressed by approximately 80%. However, after completion of each course, the lesions seemed to reappear to some degree. The patient desired to pursue further therapy; therefore, CI 5-FU at a dose of 250 mg/m2 per day (500 mg/d) was instituted, while pyridoxine was avoided in the hope of causing a hand-foot syndrome that may provide some long-term benefit. After receiving a 12-week course of therapy of CI 5-FU at 250 mg/m2 per day, his lesions were approximately 95% improved, with only a few minute punctate keratoses remaining. At follow-up nearly 4 years later, the lesions remain 90% cleared.

Asunto(s)