Treating Heart Failure with Preserved Ejection Fraction: A Challenge for Clinicians.

Despite a decline in many forms of cardiovascular disease, heart failure (HF) continues to increase. Heart failure with preserved ejection fraction (HFpEF) is common, especially among persons with multiple comorbidities. HFpEF presents many challenges for clinicians due to the incomplete understanding of the underlying mechanisms and lack of consensus on the most effective strategies for treatment. Angiotensin and beta receptor-blocking drugs, which form the cornerstone for the treatment of systolic HF, have failed to show similar benefits in patients with impaired diastolic function. This article provides an overview of drug therapy for HFpEF, including newer agents now under investigation.

Vorapaxar in atherosclerotic disease management.

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.

Association of Uninterrupted Oral Anticoagulation During Cardiac Device Implantation with Pocket Hematoma.

PURPOSE: Implantation of permanent pacemakers (PPMs) or implantable cardiac defibrillators (ICDs) may be complicated by the development of pocket hematomas. Current practice guidelines provide little guidance to clinicians about the preferred strategy for chronic oral anticoagulation (OAC). The purpose of this study was to examine the frequency and clinical significance of pocket hematoma among patients receiving uninterrupted OAC during cardiac device implantation. METHODS: This was a retrospective cohort study of adult patients undergoing cardiac device implantation between January 1, 2011, and December 31, 2012, at an academic teaching hospital. Medical records were reviewed for demographics, comorbidities, and medications. The primary outcome was development of pocket hematomas within 30 days of device implantation. Clinical significance was based on the need for additional intervention. Data were assessed using descriptive statistics, logistic regression, and chi-square tests. RESULTS: The final cohort included 380 patients. The median age was 68.4 years, and 56.6% were male. Cardiovascular comorbidities were common. Among 80 patients receiving uninterrupted OAC, 71.3% were taking warfarin, 11.2% rivaroxaban, and 17.5% dabigatran. The incidence of pocket hematomas for the entire cohort was 9.7%, of which 1.3% were clinically significant. Pocket hematoma occurred in 21.4% of patients continued on OAC versus 7.7% of those not anticoagulated (P = .001). Pocket hematoma was more common among those receiving ICDs than PPMs (18.5% vs 5.7%, respectively; P < .001). CONCLUSIONS: Continuing chronic OAC increased pocket hematoma formation but most were clinically insignificant. Pocket hematoma occurred irrespective of the oral anticoagulant drug used, but additional study is needed to determine comparative risks among the drugs.

Krill oil for cardiovascular risk prevention: is it for real?

Omega-3 fatty acids play an important role in cardiovascular health. Although it is suggested that individuals obtain these nutrients through diet, many prefer to rely on supplements. Fish oil supplements are widely used, yet large capsule sizes and tolerability make them less than ideal. Recently, krill oil has emerged as a potential alternative for omega-3 supplementation. This article will discuss what is known about krill oil and its potential use in cardiovascular risk prevention.

Diabetes and cardiovascular risk: are dipeptidyl peptidase-4 inhibitors beneficial?

Cardiovascular (CV) disease is a major cause of morbidity and mortality in patients with diabetes. Whereas the link between glycemic control and reducing microvascular disease is firmly established, the evidence for macrovascular risk reduction remains unclear. Despite a host of available drugs for lowering serum glucose, none to date have been shown to substantially reduce CV risk and some have been associated with adverse effects. Recent trials have examined the CV effects of the dipeptidyl peptidase 4 (DPP-4) inhibitors or "gliptins."

Aspirin for primary cardiovascular prevention: when is it worth the risks?

Low-dose aspirin is widely used by individuals to prevent first myocardial infarction and stroke. Although many health care professionals and patients believe that aspirin is safe and effective, the evidence is far from conclusive. As a result, current practice guidelines are inconsistent and leave practitioners with many unanswered questions. Because aspirin is available without prescription, pharmacists may often be the only health care professional positioned to advise and educate the patient.

Azithromycin-induced proarrhythmia and cardiovascular death.

OBJECTIVE: To review the possible association between azithromycin and increased cardiovascular risk. DATA SOURCES: A literature search of MEDLINE (1946-August 2013) was performed using the search terms macrolide, azithromycin, QT prolongation, cardiovascular, and torsade de pointes. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language observational studies assessing the association between azithromycin and QT prolongation or cardiovascular risk were evaluated. Case reports describing this potential association were also reviewed. DATA SYNTHESIS: A total of 6 case reports have shown a possible association between azithromycin and QT prolongation. In 3 of these cases, proarrhythmic events were reported. In a prospective observational study of 47 individuals with low cardiovascular risk, electrocardiograms were compared before and after 5 days of azithromycin treatment. Mild prolongation of the QTc was noted, but it was statistically insignificant compared with baseline. No arrhythmias were observed. A large observational cohort study found a small increase in cardiovascular deaths after azithromycin therapy, primarily among patients with high baseline cardiovascular risk. Conversely, a second cohort study involving a population of young to middle-aged adults failed to find an association. CONCLUSIONS: An emerging body of evidence suggests that azithromycin therapy may prolong the QT interval and, in rare cases, precipitate the potentially fatal arrhythmia torsade de pointes. Patients with additional risk factors for QT prolongation appear to be at highest risk, including women, elderly individuals; those with existing or prior history of cardiovascular disease, QT interval prolongation, hypokalemia, hypomagnesium, or bradycardia; and those using concomitant drugs associated with QT prolongation. For patients without these additional risk factors, azithromycin appears to be relatively safe.

Influenza vaccine for cardiovascular risk reduction.

Cardiovascular disease is a leading cause of morbidity and mortality. Individuals with underlying cardiovascular disease are at high risk for adverse outcomes from influenza infections. Although additional studies are needed, current evidence suggests the influenza vaccine may reduce the risk of cardiovascular death and coronary events. In addition to their overall efforts to encourage influenza vaccination for all eligible persons, pharmacists should pay special attention to these high-risk individuals.

New oral anticoagulants for stroke prevention in atrial fibrillation: more choices bring more challenges.

For patients with atrial fibrillation, anticoagulant therapy is essential to reduce the risk of ischemic stroke that is associated with this arrhythmia. Historically, warfarin has been the preferred treatment for patients at moderate to high risk despite many potential limitations. With the development of newer oral anticoagulants, clinicians now have 3 additional options: dabigatran, rivaroxaban, and apixaban. Although these agents clearly offer some advantages over warfarin, they may not be appropriate for all patients. This article will discuss factors that should be considered when selecting among these various anticoagulants.

Study of nonparticipation in an employee diabetes program.

OBJECTIVES: To determine factors that affect nonparticipation in an employee diabetes program and factors that may increase participation in future employee health programs. METHODS: Participants in this cross-sectional study were adults with type 1 or type 2 diabetes, 18 to 80 years of age, who were covered by employer insurance but chose not to participate in an employer-sponsored diabetes program. Potential factors affecting program participation were assessed through a face-to-face or mailed survey. RESULTS: Of 204 employees or their dependents eligible for the diabetes program, 75 (37%) chose not to participate. Among the nonparticipants, 46 (61%) were eligible for this study. A total of 22 surveys were collected for a 48% response rate. The majority of those individuals surveyed (91%) were aware of the diabetes program and had been notified by mail (42%) or phone (29%). Of those surveyed, 33% did not believe that program incentives had been sufficiently explained to them. Work schedule was not found to be a determinant of participation. More than one-half (52%) of responders identified satisfaction with their current diabetes management as the most notable reason for nonparticipation in the employee diabetes program. CONCLUSION: This study demonstrated that the primary reason for program nonparticipation was patient satisfaction with current physician management of their diabetes. In the future, companies offering health programs should emphasize that the program is being offered to supplement and complement current disease state management, not to replace it.

Community pharmacy-based medication therapy management services: financial impact for patients / Servicios de gestión de la medicación en farmacia comunitaria: impacto financiero para los pacientes

Objective: To determine the direct financial impact for patients resulting from Medication Therapy Management (MTM) interventions made by community pharmacists. Secondary objectives include evaluating the patient and physician acceptance rates of the community pharmacists’ recommended MTM interventions. Methods: This was a retrospective observational study conducted at 20 Price Chopper and Hen House grocery store chain pharmacies in the Kansas City metro area from January 1, 2010 to December 31, 2010. Study patients were Medicare Part D beneficiaries eligible for MTM services. The primary outcome was the change in patient out-ofpocket prescription medication expense as a result of MTM services. Results: Of 128 patients included in this study, 68% experienced no out-of-pocket financial impact on their medication expenses as a result of MTM services. A total of 27% of the patients realized a cost-savings (USD440.50 per year, (SD=289.69)) while another 5% of patients saw a cost increase in out-of-pocket expense (USD255.66 per year, (SD=324.48)). The net financial impact for all 128 patients who participated in MTM services was an average savings of USD102.83 per patient per year (SD=269.18, p<0.0001). Pharmacists attempted a total of 732 recommendations; 391 (53%) were accepted by both the patient and their prescriber. A total of 341 (47%) recommendations were not accepted because of patient refusal (290, 85%) or prescriber refusal (51, 15%). Conclusions: Patient participation in MTM services reduces patient out-of-pocket medication expense. However, this savings is driven by only 32% of subjects who are experiencing a financial impact on out-of-pocket medication expense. Additionally, the majority of the pharmacists’ recommended interventions (53%) were accepted by patients and prescribers (AU)

Objetivo: Determinar el impacto financiero directo para los pacientes resultando de las intervenciones de Gestión de la Medicación (MTM) hechas por farmacéuticos comunitarios. Los objetivos secundarios incluían evaluar las tasas de aceptación por pacientes y médicos de las recomendaciones de MTM de los farmacéuticos. Métodos: Fue un estudio observacional retrospectivo realizado en 20 tiendas de la cadena de farmacias Price Chopper and Hen House de la zona metropolitana de Kansas City desde 1 de enero 2010 a 31 de diciembre 2010. Los pacientes en estudio eran beneficiarios de Medicare Part D elegibles para servicios de MTM. El resultado primario fue los cambios en gastos sufragados por los pacientes de la medicación prescrita como resultado de los servicios de MTM. Resultados: De los 128 pacientes incluidos en el estudio, el 68% no experimentó impacto en sus gastos en medicación como resultado de los servicios de MTM. Un 27% de los pacientes consiguió un ahorro (USD440,50 por año, (SD=289,69)) mientras que otro 5% de pacientes vio incrementado su gasto en medicación (USD255,66 por año, (SD=324,48)). El impacto financiero neto para los 128 pacientes que participaron en el estudio fue un ahorro medio de USD102,83 por paciente y año (SD=269,18; p<0,0001). Los farmacéuticos intentaron un total de 732 recomendaciones; 391 (53%) fueron aceptadas tanto por pacientes como por prescriptor. Un total de 341 (47%) recomendaciones no fueron aceptadas, por negativa del paciente (290; 85%) o por negativa del prescriptor (51; 15%). Conclusiones: La participación de los pacientes en servicios de MTM reduce el gasto en medicamentos del paciente. Sin embargo, este ahorro se materializa sólo en un 32% de pacientes que sufren impacto financiero. Asimismo, la mayoría (53%) de las intervenciones recomendadas por el farmacéutico fueron aceptadas por pacientes y prescriptores (AU)

Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines.

BACKGROUND: The risk of stroke varies considerably across different groups of patients with atrial fibrillation (AF). Antithrombotic prophylaxis for stroke is associated with an increased risk of bleeding. We provide recommendations for antithrombotic treatment based on net clinical benefit for patients with AF at varying levels of stroke risk and in a number of common clinical scenarios. METHODS: We used the methods described in the Methodology for the Development of Antithrombotic Therapy and Prevention of Thrombosis Guidelines: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines article of this supplement. RESULTS: For patients with nonrheumatic AF, including those with paroxysmal AF, who are (1) at low risk of stroke (eg, CHADS(2) [congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, prior stroke or transient ischemic attack] score of 0), we suggest no therapy rather than antithrombotic therapy, and for patients choosing antithrombotic therapy, we suggest aspirin rather than oral anticoagulation or combination therapy with aspirin and clopidogrel; (2) at intermediate risk of stroke (eg, CHADS(2) score of 1), we recommend oral anticoagulation rather than no therapy, and we suggest oral anticoagulation rather than aspirin or combination therapy with aspirin and clopidogrel; and (3) at high risk of stroke (eg, CHADS(2) score of ≥ 2), we recommend oral anticoagulation rather than no therapy, aspirin, or combination therapy with aspirin and clopidogrel. Where we recommend or suggest in favor of oral anticoagulation, we suggest dabigatran 150 mg bid rather than adjusted-dose vitamin K antagonist therapy. CONCLUSIONS: Oral anticoagulation is the optimal choice of antithrombotic therapy for patients with AF at high risk of stroke (CHADS(2) score of ≥ 2). At lower levels of stroke risk, antithrombotic treatment decisions will require a more individualized approach.

Community pharmacy-based medication therapy management services: financial impact for patients.

OBJECTIVE: To determine the direct financial impact for patients resulting from Medication Therapy Management (MTM) interventions made by community pharmacists. Secondary objectives include evaluating the patient and physician acceptance rates of the community pharmacists' recommended MTM interventions. METHODS: This was a retrospective observational study conducted at 20 Price Chopper and Hen House grocery store chain pharmacies in the Kansas City metro area from January 1, 2010 to December 31, 2010. Study patients were Medicare Part D beneficiaries eligible for MTM services. The primary outcome was the change in patient out-of-pocket prescription medication expense as a result of MTM services. RESULTS: Of 128 patients included in this study, 68% experienced no out-of-pocket financial impact on their medication expenses as a result of MTM services. A total of 27% of the patients realized a cost-savings (USD440.50 per year, (SD=289.69)) while another 5% of patients saw a cost increase in out-of-pocket expense (USD255.66 per year, (SD=324.48)). The net financial impact for all 128 patients who participated in MTM services was an average savings of USD102.83 per patient per year (SD=269.18, p<0.0001). Pharmacists attempted a total of 732 recommendations; 391 (53%) were accepted by both the patient and their prescriber. A total of 341 (47%) recommendations were not accepted because of patient refusal (290, 85%) or prescriber refusal (51, 15%). CONCLUSIONS: Patient participation in MTM services reduces patient out-of-pocket medication expense. However, this savings is driven by only 32% of subjects who are experiencing a financial impact on out-of-pocket medication expense. Additionally, the majority of the pharmacists' recommended interventions (53%) were accepted by patients and prescribers.

Vitamin D deficiency and supplementation and relation to cardiovascular health.

Recent evidence supports an association between vitamin D deficiency and hypertension, peripheral vascular disease, diabetes mellitus, metabolic syndrome, coronary artery disease, and heart failure. The effect of vitamin D supplementation, however, has not been well studied. We examined the associations between vitamin D deficiency, vitamin D supplementation, and patient outcomes in a large cohort. Serum vitamin D measurements for 5 years and 8 months from a large academic institution were matched to patient demographic, physiologic, and disease variables. The vitamin D levels were analyzed as a continuous variable and as normal (≥30 ng/ml) or deficient (<30 ng/ml). Descriptive statistics, univariate analysis, multivariate analysis, survival analysis, and Cox proportional hazard modeling were performed. Of 10,899 patients, the mean age was 58 ± 15 years, 71% were women (n = 7,758), and the average body mass index was 30 ± 8 kg/m(2). The mean serum vitamin D level was 24.1 ± 13.6 ng/ml. Of the 10,899 patients, 3,294 (29.7%) were in the normal vitamin D range and 7,665 (70.3%) were deficient. Vitamin D deficiency was associated with several cardiovascular-related diseases, including hypertension, coronary artery disease, cardiomyopathy, and diabetes (all p <0.05). Vitamin D deficiency was a strong independent predictor of all-cause death (odds ratios 2.64, 95% confidence interval 1.901 to 3.662, p <0.0001) after adjusting for multiple clinical variables. Vitamin D supplementation conferred substantial survival benefit (odds ratio for death 0.39, 95% confidence interval 0.277 to 0.534, p <0.0001). In conclusion, vitamin D deficiency was associated with a significant risk of cardiovascular disease and reduced survival. Vitamin D supplementation was significantly associated with better survival, specifically in patients with documented deficiency.

P2Y12 receptor inhibitors: integrating ticagrelor into the management of acute coronary syndrome.

Acute coronary syndrome (ACS) is a continuum of disease that includes non-ST-segment elevation ACS and ST-segment elevation myocardial infarction. The purpose of this article is to define the developing role of ticagrelor in ACS and compare it to currently available P2Y12 receptor inhibitors. While clopidogrel remains the "workhorse" P2Y12 receptor inhibitor for many patients with ACS and prasugrel has an established role in select situations, clinicians must now assimilate the evolving role of ticagrelor. Although ticagrelor offers important advances in the management of ACS (eg, reversibility), there are also notable clinical considerations (eg, unique adverse effects such as dyspnea). Based on the current evidence, we propose an algorithm to aid clinicians in the selection of a P2Y12 receptor inhibitor for patients with ACS in various clinical situations.

Preoperative Statin use is not Associated with a Reduced Risk of Atrial Fibrillation After Cardiac Surgery.

Introduction: Postoperative atrial fibrillation (POAF) is prevalent after cardiac surgery and associated with significant morbidity and costs. Statins are commonly used in this population and may be a preventative strategy for PAOF. We wished to examine the effect of preoperative statin use on the risk of POAF after cardiac surgery. Methods: A retrospective, observational study was conducted using data from 489 adult patients who underwent cardiac surgery at a single institution. Univariate analyses and unconditional logistic regression were used to determine the impact of preoperative statin use on the probability of developing POAF, while controlling for the baseline risk of POAF and the use of amiodarone prophylaxis (AMP). A baseline risk index was calculated for each patient using a previously validated model. Patients with chronic atrial fibrillation or missing data were excluded. Results: Mean patient age was 63 (SD=13) years, 73% were male, 68% underwent isolated coronary artery bypass grafting, 16% underwent isolated valve surgery, with 13% underwent combined CABG and valve surgeries, and 3% underwent other forms of cardiac surgery. POAF occurred in 27% of patients receiving statins and 24% of those not receiving statins (p=0.3792). After controlling for baseline risk of POAF and the use of AMP, we found that preoperative statins were not associated with reductions in POAF (OR=1.19, 95%CI=0.782-1.822, p=0.4118). Conclusions: Multiple factors impact the development of POAF after cardiac surgery including patient demographics, comorbidities, surgical type, and concomitant medications. In this study, after adjustment for these factors the preoperative use of statins did not significantly influence the development of POAF.

Impact of bisphosphonates on the risk of atrial fibrillation.

Osteoporosis is a major public health problem resulting in significant morbidity, mortality, and utilization of healthcare resources. Bisphosphonates are the most widely prescribed drugs for increasing bone mass and preventing osteoporosis-related fractures. Although these drugs have proven efficacy and are generally considered safe, a clinical trial of once-yearly zoledronic acid reported an unexpected increase in the risk of cardiac arrhythmias, primarily due to serious atrial fibrillation (AF). Subsequently, a post hoc analysis of another clinical trial reported a nonsignificant trend toward an increased risk of serious AF. Based on these concerns, the US FDA issued a cautionary advisory and is conducting an ongoing safety review. A major limitation of the clinical trials was the fact that none were designed or powered to evaluate arrhythmia endpoints. In search of more definitive answers, several observational studies using both population-based cohort and case-control designs have attempted to verify this association. However, only two studies, one cohort and one case-control study, have found a positive association, while six additional studies have reported negative findings. While most of the observational studies attempted to control for confounders, the chosen variables have varied considerably, and other key potential confounders such as smoking were not controlled for in any of the studies. Because the occurrence of AF events in the studies was relatively low, four meta-analyses have been conducted to increase sample size by using pooled data from multiple studies. Again, results have been inconsistent, with two of the analyses reporting a significant increase in serious AF and two finding no association. Additionally, no direct evidence has identified any underlying mechanism to explain an increased arrhythmia risk with bisphosphonate therapy. However, several possible mechanisms have been proposed, including an activated inflammatory state, altered electrolytes impacting cardiac conduction, and long-term atrial structural changes. Due to the widespread use of bisphosphonates in a population for whom the baseline risk of AF also increases with advancing age, further prospective assessment of this possible association is clearly warranted. If an association does exist between bisphosphonates and an increased risk for AF, several additional questions will need to be answered including impact of baseline risk, the time course for increased risk, relationship to drug dose, and whether or not this represents a drug-class adverse effect. Until definitive evidence is available, clinicians will continue to have to make clinical judgments based on the available and often inconsistent evidence to date. To provide further perspective on this possible association, we performed a systematic search of the PubMed database from 1966 to 30 June 2010, drug regulatory websites, and drug manufacturer websites. In this review we summarize the findings from clinical trials, observational studies, and meta-analyses evaluating the risk of AF following bisphosphonate exposure, and discuss possible mechanisms that could explain an increased risk.

Role of vitamin D in cardiovascular health.

Observational studies strongly associate vitamin D deficiency with a variety of cardiovascular diseases beyond defects in bone and calcium metabolism. Vitamin D has multiple mechanisms that potentially may affect cardiovascular health. Because vitamin D deficiency is common, therapies directed at the replacement of vitamin D may be beneficial. To date however, studies evaluating vitamin D supplementation are few and have not consistently shown benefit. It is possible that the lack of benefit in these studies may have arisen from suboptimal levels of vitamin D supplementation or other unknown factors. Nevertheless, the growing body of observational data and consistent findings of relatively high rates of low vitamin D serum levels warrant further well-designed studies to investigate the relation between vitamin D and cardiovascular health. In conclusion, vitamin D is now recognized as important for cardiovascular health and its deficiency as a potential risk factor for several cardiovascular disease processes.