Heart Failure with Preserved Left Ventricular Ejection Fraction: A Complex Conundrum Simply Not Limited to Diastolic Dysfunction.

Over the last two decades, the changing paradigm of heart failure with preserved ejection fraction (HFpEF) has transformed our understanding not only of the pathophysiology of this clinical entity but also the diagnostic and therapeutic approaches aimed at treating this complex patient population. No longer HFpEF should be seen as simply left ventricular diastolic dysfunction but as a group of that in addition of having small and thick left ventricles with abnormal diastolic filling patterns as their main pathophysiologic abnormality; they also have whole host of different abnormalities. In fact, this heterogeneous clinical entity embodies numerous mechanisms and is linked to multiorgan dysfunction, with hypertension and obesity playing a major role.

Growth Differentiation Factor 15 (GDF-15), a New Biomarker in Heart Failure Management.

The emergence of biomarkers across medicine's subspecialties continues to evolve. In essence, a biomarker is a biological observation that clearly substitutes a clinical endpoint or intermediate outcome not only are more difficult to observe but also, biomarkers are easier, less expensive and could be measured over shorter periods. In general, biomarkers are versatile and not only used for disease screening and diagnosis but, most importantly, for disease characterization, monitoring, and determination of prognosis as well as individualized therapeutic responses.

Obesity and Altered Aspirin Pharmacology.

Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy. Central to the obesity-related risk of atherothrombosis is a pro-thrombotic state characterized by increased levels of coagulation factors, impaired fibrinolysis, and platelet hyper-reactivity, which results from the interaction among the features clustering in obesity: insulin resistance, inflammation, oxidative stress, and endothelial dysfunction. Aspirin is a cornerstone antiplatelet drug that has substantial interpatient variability in pharmacodynamic response and a number of reports have demonstrated that obesity is a risk factor for a reduced aspirin pharmacodynamic response.

Aspirin responsiveness changes in obese patients following bariatric surgery.

Aims: Bariatric surgery has emerged as a promising treatment option for weight loss and to counter the metabolic consequences of obesity. Obesity has been linked to a hyperaggregable state, as well as a blunted response to aspirin. This pilot study assessed the hypothesis that bariatric surgery would lead to an improvement in aspirin-induced platelet inhibition and a reduction in platelet aggregability.

Obesity and Inflammation and Altered Clopidogrel Pharmacokinetics and Pharmacodynamics.

Background: Clopidogrel is a key antiplatelet drug that has substantial interpatient variability in pharmacodynamic response. Patients with lesser degrees of platelet inhibition in response to clopidogrel appear to be at increased risk of cardiovascular events. Obesity is an independent risk factor for cardiovascular morbidity and mortality due to atherothrombotic events and represents a group of patients who are in need of optimized antithrombotic therapy.

Towards Precision in HF Pharmacotherapy.

Purpose Of Review: Heart failure (HF) is a disease state with great heterogeneity, which complicates the therapeutic process. Identifying more precise HF phenotypes will allow for the development of more targeted therapies and improvement in patient outcomes. This review explores the future for precision medicine in HF treatment.

The Importance of Research and Scholarly Activity in Pharmacy Training.

Regardless of practice setting, it is imperative that pharmacists be able to either participate in generating new knowledge or use the ever-expanding body of literature to guide patient care. However, competing priorities in Pharm.D.

Sequential Evolution of Vancomycin-Intermediate Resistance Alters Virulence in Staphylococcus aureus: Pharmacokinetic/Pharmacodynamic Targets for Vancomycin Exposure.

Staphylococcus aureus possesses exceptional virulence and a remarkable ability to adapt in the face of antibiotic therapy. We examined the in vitro evolution of S. aureus in response to escalating vancomycin exposure by evaluating bacterial killing and the progression of resistance.

Oral Administration of Sustained Release Niacin Inhibits Platelet Aggregation.

Background: Previous studies have suggested that niacin may have antiplatelet properties, however the effects of niacin on the platelet activity are not well defined.

Objective: The purpose of this trial was to investigate whether the oral administration of niacin inhibits platelet aggregation.

Method: This study was run in three segments measuring the inhibitory effect of niacin: 1) 3 mmol/L niacin in vitro, 2) one hour after 1-gram sustained-release (SR) niacin administration, 3) twelve hours after 2-gram SR niacin administration.

P2Y12 antagonists in non-ST-segment elevation acute coronary syndromes: latest evidence and optimal use.

Dual antiplatelet therapy (DAPT), which includes the combination of aspirin and a P2Y12 platelet receptor inhibitor, is a well-established antiplatelet regimen in the treatment of patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS). Three P2Y12 inhibitor options (clopidogrel, prasugrel and ticagrelor) are currently available, all having different efficacy and safety profiles along with contrasting contraindications, special warnings and precautions for use. This review compares and contrasts the unique P2Y12 antagonists in the NSTE-ACS setting, covering the latest evidence and their optimal use.

Optimal aspirin dose in acute coronary syndromes: an emerging consensus.

Numerous clinical trials testing the efficacy of aspirin for the secondary prevention of cardiovascular disease have been published. We reviewed the literature pertaining to aspirin dose in acute coronary syndrome patients. Clinical trials assessing the comparative efficacy of different doses of aspirin are scarce.

Clopidogrel, prasugrel, or ticagrelor? a practical guide to use of antiplatelet agents in patients with acute coronary syndromes.

Aspirin is a cornerstone of therapy in the treatment of patients with acute coronary syndromes (ACS). However, dual antiplatelet therapy reduces the risk of stent thrombosis and cardiovascular events compared with aspirin alone in the treatment of patients with ACS. Recently, there has been debate as to which antiplatelet agent should be added to aspirin in the ACS treatment regimen.

Novel anticoagulants in atrial fibrillation stroke prevention.

This review article evaluates novel oral anticoagulants in comparison with warfarin for thromboembolism prophylaxis in patients with atrial fibrillation (AF). AF is the most frequently diagnosed arrhythmia in the United States. The most serious side effect of AF is stroke.

Future of personalized pharmacotherapy in chronic heart failure patients.

There is a significant amount of diversity among heart failure (HF) patients. Contemporary HF regimens often do not take into consideration many of the factors that might influence an individual's response to treatment. Clinical recommendations based on trial data derived from mainly younger Caucasian male study populations have, in most cases, been applied equally to women and African-Americans.

Rhabdomyolysis in a patient receiving high-dose simvastatin after the induction of therapeutic hypothermia.

Objective: To report a case of rhabdomyolysis in a patient receiving high-dose simvastatin after the induction of therapeutic hypothermia.

Case Summary: A 45-year-old African American male was brought to the emergency department for a witnessed cardiac arrest. He was placed on a therapeutic hypothermia protocol and his simvastatin dose was increased from 40 to 80 mg at bedtime.

The in vitro effects of niacin on platelet biomarkers in human volunteers.

Niacin is a natural pyridine derivative, proven to favorably modulate the blood lipid profile by increasing levels of high-density lipoprotein (HDL) cholesterol, and by reducing total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, and Lp (a) lipoprotein concentrations. Considering that platelet activity is important in predicting vascular outcomes, and that HDL heavily constitutes platelet cellular membranes, we sought to evaluate the effect of niacin on human platelet activity indices. The blood obtained from 30 aspirin-naïve volunteers was preincubated with escalating concentrations of niacin in vitro.

Profound thrombocytopenia after primary exposure to eptifibatide.

Eptifibatide is a glycoprotein IIb/IIIa receptor antagonist used to reduce the incidence of ischemic events in patients with acute coronary syndromes and those undergoing percutaneous coronary intervention. A minority of patients given eptifibatide develop acute, profound thrombocytopenia (<20,000 cells/mm(3)) within a few hours of receiving the drug. This case report discusses a patient who developed profound thrombocytopenia within hours of receiving eptifibatide for the first time.

Comparison of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

Antiplatelet agents are the cornerstone of treatment for patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Clopidogrel, when added to aspirin, has demonstrated considerable success at reducing thrombotic complications of ACS and/or PCI compared to aspirin alone and is standard of care for the management of patients with ACS and in patients undergoing PCI. Prasugrel is a novel thienopyridine antiplatelet agent recently approved for the treatment of patients with ACS undergoing PCI.

Cangrelor: a novel P2Y12 receptor antagonist.

Antiplatelet therapy is critical in the prevention of thrombotic complications of acute coronary syndrome and percutaneous coronary interventions. Current antiplatelet agents (aspirin, clopidogrel and glycoprotein IIb/IIIa antagonists) have demonstrated the capacity to reduce major adverse cardiac events. However, these agents have limitations that compromise their clinical utility.

Drug-drug interaction between clopidogrel and the proton pump inhibitors.

Objective: To evaluate the interaction between clopidogrel and proton pump inhibitors (PPIs).

Data Sources: Literature retrieval was accessed through PubMed (1980-January 2009), abstracts from 2008 American Heart Association and 2009 Society of Cardiovascular Angiography and Interventions Scientific Sessions, and media press releases using the terms clopidogrel, proton pump inhibitors, cytochrome 2C19, genetic cytochrome P450 polymorphisms, and drug interaction. In addition, reference citations from publications identified in the search were reviewed.

Clopidogrel attenuates coated-platelet production in patients undergoing elective coronary catheterization.

Introduction: Coated-platelets are a subclass of highly thrombotic activated platelets with an enhanced ability to generate thrombin. Excessive numbers of coated-platelets are believed to increase thrombotic risk. A previous report demonstrated that P2Y12 inhibition in vitro attenuates coated-platelet formation.