Jennifer Campbell

New and emerging anticoagulant therapy for atrial fibrillation and acute coronary syndrome.

Thrombosis is an underlying cause of many cardiovascular disorders, and generation of thrombi in the arterial circulation can lead to unstable angina, myocardial infarction, or ischemic stroke. Antithrombotic therapy is widely used, with proven benefit to prevent ischemic stroke and thromboembolic events in patients with atrial fibrillation (AF) or to prevent further ischemic complications in patients with acute coronary syndrome (ACS). Traditional anticoagulants (including unfractionated heparin, low‐molecular‐weight heparin, and warfarin) and antiplatelet agents (including aspirin, clopidogrel, and prasugrel) are typically used for these indications. Limitations to their use include variable pharmacokinetic and pharmacodynamic profiles, inability to inhibit fibrin‐bound thrombin, risk of heparin‐induced thrombocytopenia, delayed onset of action, numerous drug interactions, need for substantial laboratory monitoring and dosage titrations, hyporesponsiveness or resistance, hypersensitivity, adverse events, and bleeding. To overcome some of the limitations of traditional agents, new antithrombotic agents under development are highly selective for specific coagulation factors blocking the synthesis of thrombin. Clinicians must have an understanding of the new anticoagulants to aid in the selection of appropriate therapies for patients. We describe the most relevant phases II and III clinical trials that evaluated several recent emerging anticoagulant drugs for use in patients with AF or ACS. The advantages of many new agents include predictable pharmacodynamic response and pharmacokinetic parameters, allowing for fixed oral dosing with no need for laboratory monitoring. For patients with AF, dabigatran is already approved for the prevention of stroke and systemic embolism, rivaroxaban appears to be an effective alternative to warfarin in high‐risk patients, and apixaban may also be an effective alternative to aspirin in patients unable to take warfarin. Otamixaban shows promise as an intravenous alternative for patients with ACS in the acute care setting. Likewise, rivaroxaban, dabigatran, and darexaban with or without dual antiplatelet therapy may be beneficial for secondary prevention of ischemic events in patients with ACS.

Efficacy, safety, and cost of thrombolytic agents for the management of dysfunctional hemodialysis catheters: a systematic review.

Approximately 100,000 patients begin hemodialysis each year in the United States. Although an arteriovenous fistula or graft is the preferred method for long‐term vascular access during hemodialysis, as these types of vascular access are the most reliable, approximately 30% of patients require the use of catheters to continue hemodialysis. Tunneled, cuffed hemodialysis catheters are discouraged for permanent vascular access because of their high rates of infection, morbidity and mortality, and thrombotic and technical complications. These catheters have a short functional life span and require medical intervention, often thrombolytic therapy, to treat the catheter malfunction. No thrombolytic agent is specifically indicated for the management of occluded hemodialysis catheters. Thus, we performed a systematic review to critically evaluate all available studies that examined the efficacy, safety, and cost of thrombolytic therapy for the management of dysfunctional hemodialysis catheters. Studies were included if they reported efficacy in a specific proportion of affected dysfunctional hemodialysis catheters; reported the proportion of patients experiencing an adverse outcome (especially bleeding); and described the type of catheter used, dose of thrombolytic agent, administration protocol, dwell time, definition of treatment success, time to follow‐up for study end points, and sample size. Eighteen studies met the inclusion criteria. The mean ± SD success rate in clearing dysfunctional hemodialysis catheters was greatest with reteplase at 88 ± 4%, followed by alteplase at 81 ± 37% and tenecteplase at 41 ± 5%. Adverse effects associated with the use of these thrombolytic agents administered at low doses were extremely rare. No serious adverse bleeding events attributed to thrombolytic therapy were reported in any of the trials. Aliquotted reteplase from vials for intravenous use was the least costly thrombolytic agent. Thus, at centers that use high volumes of thrombolytics for dysfunctional hemodialysis catheters, reteplase is the thrombolytic agent of choice.

Emerging Antiplatelet Therapy for Coronary Artery Disease and Acute Coronary Syndrome

Antiplatelet therapy is used widely with proven benefit for the prevention of further ischemic cardiac complications in patients with known coronary artery disease (CAD) and a history of acute coronary syndrome (ACS). The limitations of conventional antiplatelet therapy with aspirin, clopidogrel, or prasugrel, as well as the fact that rates of recurrent ischemic events still remain high with use of these agents, underscore the need to investigate alternate agents that may further reduce event rates while limiting bleeding risk. The selection of antiplatelet therapy is further influenced by the following: ticagrelor was approved in July 2011 by the United States Food and Drug Administration (FDA),and clopidogrel is slated to become available as a generic productin 2012. We provide an overview of emerging agents for the treatment of CAD and ACS, including the reversible P2Y12 antagonists ticagrelor, cangrelor, and elinogrel, and a new class of oral protease‐activated receptor‐1 (PAR‐1) inhibitors, vorapaxar and atopaxar.The recentlyapproved P2Y12 antagonists prasugrel and ticagrelor demonstrate enhanced ability to prevent adverse cardiac outcomes. However, this comes at a cost of a potential increased risk of bleeding. New adverse effects have also emerged, including dyspnea for all of the reversible P2Y12 antagonists (ticagrelor, cangrelor, and elinogrel) and ventricular pauses for ticagrelor. In addition, the newer P2Y12 antagonists have a faster onset and offset. Two of these agents, cangrelor and elinogrel, are available as intravenous formulations, which may provide additional benefits in patients whoundergo coronary artery bypass graft (CABG) surgery. Trials with the PAR‐1 inhibitors have also shown trends toward reductions in cardiac events, but not without the possibility of increased bleeding. More than ever, as the arsenal of antiplatelet therapy expands, health care providers need to understand the pharmacologic and pharmacodynamic differences between conventional and emerging antiplatelet therapies forpatients with ACS and CAD. Health care providers must also carefully assess patient‐specific factors such as risk of thrombosis, concomitant disease states, age, drug adherence, and aspirin dose, and plan for those patients who will be undergoing CABG when selecting antiplatelet therapy in order to optimally balance bleeding and thrombosis risk.

Recombinant peptides in thrombolysis.

Recombinant thrombolytic peptides are mainly represented by recombinant forms of tissue plasminogen activator (t-PA), a proteolytic enzyme that catalyzes the conversion of plasminogen into active plasmin, which then functions to dissolve clots. The three clinically relevant recombinant thrombolytic peptides are alteplase (t-PA), reteplase (r-PA), and tenecteplase (TNK). r-PA and TNK have been structurally modified from native t-PA to increase their half-life and fibrin specificity. Thrombolytics play an important role in several diseases, including ST-segment elevation myocardial infarction (STEMI), deep vein thrombosis (DVT) and pulmonary embolism (PE), ischemic stroke, and peripheral arterial disease. Thrombolytic therapy has evolved into an alternative treatment for STEMI, reserved predominantly for patients who do not have access to timely percutaneous coronary intervention. In patients with DVT/PE or arterial related critical limb ischemia, the use of thrombolytic therapy is limited to specific patient populations. Thrombolytic therapy is the treatment of choice for ischemic stroke in patients who present <or=3 hours following the onset of symptoms. Moreover, thrombolytic therapy is used to restore function to stenotized central venous access devices as well as occluded hemodialysis access grafts.

Medication Adherence in Heart Failure

Medication adherence in heart failure is especially complex due to the nature of the syndrome. Heart failure develops secondary to a wide variety of etiologies and covers a broad spectrum of symptom severity. Heart failure is commonly accompanied by coronary artery disease, hypertension, dyslipidemia, atrial fibrillation, and diabetes mellitus. As a result, patients with heart failure take medications not only for heart failure, but also for a number of other medical conditions. Hence, polypharmacy is common in heart failure patients. Reported medication adherence rates in patients with heart failure have ranged from 2% to 90% reflecting the broad range of types of patients who have heart failure and the differing methods used to assess adherence. A number of barriers to good adherence have been identified in patients with heart failure. Strategies to overcome these barriers have been described, but are often focused on single aspects of improving adherence, which tend to produce relatively small improvements in overall medication adherence. The most productive strategies to improve adherence typically involve multifactorial, multidisciplinary interventions. Disease management programs for heart failure, although not specifically designed to focus only on medication adherence, have been shown to improve adherence to a number of treatments including medications, diet, and exercise. Disease management programs have also been shown to favorably impact the frequency of heart failure hospitalizations and mortality in selected populations of heart failure patients. Efforts continue to define the most appropriate strategies to produce improvements in medication adherence in patients with heart failure.

Cost-Effectiveness of Glycemic Control

Diabetes mellitus affects approximately 24 million people in America. Analysis of the economic cost of diabetes in the USA are an estimated

Current trends in the treatment of asthma: focus on the simultaneous administration of salmeterol/fluticasone

174 billion. Type 2 diabetes results from numerous causes and most highly associated causative factors being lifestyle choices. Dietary and exercise practices can increase or decrease one’s chance of developing type 2 diabetes. The cornerstones of preventing and treating type 2 diabetes, lifestyle modification and medication therapy, are aimed at maintaining optimal blood glucose levels. There is clear evidence of benefit that tight glycemic control decreases diabetes related complications and costs. Lifestyle modification is considered first line therapy for treatment and prevention of type 2 diabetes. The progressive nature of diabetes often requires the use of drug therapy to achieve glycemic targets. Tight glycemic control provides a cost effective means of reducing unnecessary health care expenses. Identifying ways to contain health care costs and obtain high value for our health care investments continues to be a priority.

Implementing an Action Plan

Asthma is a chronic disease of the airways that affects over 20 million people in the United States. It is a complex disease that involves airway infiltration by different types of cells and cell mediators causing chronic inflammation of the airway as well as hyper-responsiveness and edema. Management of asthma symptoms often requires combination therapy with multiple medications. Long-acting beta-2 agonists and inhaled corticosteroids have become key medications in the prevention of asthma exacerbations. The bronchodilatory effects of the beta-2 agonists coupled with the anti-inflammatory action of the corticosteroids combat the multi-factorial causes of asthma. The combination inhaler containing salmeterol and fluticasone is one such product that has been proven safe and effective for asthma therapy.