Eva Rybak

A growing number of patients with an indication for stroke prevention in atrial fibrillation have kidney-, age-, or weight-related alterations in pharmacokinetics that affect dosing of direct oral anticoagulants. Because these patients were excluded from or comprised a small number of patients in clinical trials, there is a lack of evidence to guide clinicians. As a consequence, many patients do not receive oral anticoagulation despite a high risk for atrial fibrillation-related stroke. Here… Show more

A growing number of patients with an indication for stroke prevention in atrial fibrillation have kidney-, age-, or weight-related alterations in pharmacokinetics that affect dosing of direct oral anticoagulants. Because these patients were excluded from or comprised a small number of patients in clinical trials, there is a lack of evidence to guide clinicians. As a consequence, many patients do not receive oral anticoagulation despite a high risk for atrial fibrillation-related stroke. Here, we present a review of direct oral anticoagulant pharmacokinetics and a review of the available clinical evidence in patients with weight-, kidney-, and age-related disease. Show less

BACKGROUND:

The U.S. Food and Drug Administration recently approved a four-factor prothrombin complex concentrate (4-PCC) for warfarin reversal. The literature supporting its use over three-factor prothrombin complex concentrate (3-PCC) is limited.

OBJECTIVE:

Our objective was to retrospectively compare the efficacy of 3-PCC to 4-PCC in reversing warfarin in patients who were actively bleeding.

METHODS:

We conducted a single-center, retrospective cohort… Show more

BACKGROUND:

The U.S. Food and Drug Administration recently approved a four-factor prothrombin complex concentrate (4-PCC) for warfarin reversal. The literature supporting its use over three-factor prothrombin complex concentrate (3-PCC) is limited.

OBJECTIVE:

Our objective was to retrospectively compare the efficacy of 3-PCC to 4-PCC in reversing warfarin in patients who were actively bleeding.

METHODS:

We conducted a single-center, retrospective cohort analysis of adult patients who received 3-PCC or 4-PCC for international normalized ratio (INR) reversal. Our study excluded patients not actively bleeding and not on warfarin. The main outcome was the percentage of patients who achieved warfarin reversal defined as INR ≤ 1.3 at first INR check post factor administration. We recorded baseline data including PCC dose, location of bleed, pre- and posttreatment INR, and time to INR reversal.

RESULTS:

We included a total of 53 patients. Intracranial hemorrhage was the most common site of bleeding (26 [74.3%] in 3-PCC vs. 12 [66.7%] in 4-PCC). The mean dose of 3-PCC was 25.5 units/kg, compared to 27.9 units/kg of 4-PCC. The mean baseline INR was 2.3 in the 3-PCC group and 3 in the 4-PCC group (p = 0.03), and the first posttreatment INRs were 1.4 and 1.2, respectively (p < 0.01). Warfarin reversal was achieved in 15 (42.9%) patients who received 3-PCC and 15 (83.3%) patients who received 4-PCC (p < 0.01). Faster time to INR reversal was noted in the 4-PCC group vs. the 3-PCC group (3.7 vs. 5 h, p = 0.48).

CONCLUSION:

A higher percentage of patients achieved warfarin reversal with 4-PCC compared to 3-PCC treatment. A prospective randomized control trial is necessary to confirm our results.
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Submassive pulmonary embolism (PE) is characterized by hemodynamic stability with evidence of right ventricular dysfunction or myocardial necrosis, and represents a heterogeneous population at risk for adverse outcomes. Although patients with this subtype of PE are at higher risk of death, it is unclear whether escalation of care with fibrinolytic therapy mitigates this risk. The controversial role of fibrinolytic therapy for submassive PE is driven by a paucity of data, conflicting results… Show more

Submassive pulmonary embolism (PE) is characterized by hemodynamic stability with evidence of right ventricular dysfunction or myocardial necrosis, and represents a heterogeneous population at risk for adverse outcomes. Although patients with this subtype of PE are at higher risk of death, it is unclear whether escalation of care with fibrinolytic therapy mitigates this risk. The controversial role of fibrinolytic therapy for submassive PE is driven by a paucity of data, conflicting results from clinical trials, and lack of reliable positive predictive markers of mortality in this population. When compared with anticoagulation therapy alone, systemic fibrinolytic therapy leads to a more rapid improvement in pulmonary artery hemodynamics, restoration of right ventricular function, improved lung perfusion, and fewer episodes of clinical deterioration. The clinical significance of these findings remains uncertain because fibrinolytic therapy has not been demonstrated to improve mortality or reduce recurrent PE in patients with submassive PE. However, it is unclear whether this reflects methodological limitations such as small sample size and rescue fibrinolytic therapy in those assigned placebo, the absence of benefit in all patients with submassive PE, or the benefit is limited to an undefined, high-risk subset. The decision to administer adjunctive fibrinolytics in patients with submassive PE should be made on an individual basis, with serious consideration given to those with severe PE-related clinical manifestations and an acceptable risk of bleeding. Show less

Roux-en-Y gastric bypass is the most commonly performed bariatric procedure. It is associated with nutritional deficiencies due to gastric reduction, intestinal bypass, reduced caloric intake, avoidance of nutrient-rich foods, noncompliance with supplementation and poor food tolerability. Although there are multiple publications on this topic, there is a lack of consistent guidance for the healthcare practitioner caring for the bariatric patient. This article will encompass literature reviewing… Show more

Roux-en-Y gastric bypass is the most commonly performed bariatric procedure. It is associated with nutritional deficiencies due to gastric reduction, intestinal bypass, reduced caloric intake, avoidance of nutrient-rich foods, noncompliance with supplementation and poor food tolerability. Although there are multiple publications on this topic, there is a lack of consistent guidance for the healthcare practitioner caring for the bariatric patient. This article will encompass literature reviewing the pharmacotherapy approach to prevention and management of nutritional deficiencies since the American Society of Metabolic and Bariatric Surgery guidelines were published in 2008. Show less

Methylene blue has been used not only as a diagnostic agent, but also as an agent in the treatment of ifosfamide-induced encephalopathy (IIE) for several years. Recently, several cases of suspected serotonin syndrome have been reported in patients who received methylene blue in combination with serotonin active agents. Rodent models have revealed that methylene blue is a potent, reversible inhibitor of monoamine oxidase A. It is well known that serotonin active drugs, in combination with… Show more

Methylene blue has been used not only as a diagnostic agent, but also as an agent in the treatment of ifosfamide-induced encephalopathy (IIE) for several years. Recently, several cases of suspected serotonin syndrome have been reported in patients who received methylene blue in combination with serotonin active agents. Rodent models have revealed that methylene blue is a potent, reversible inhibitor of monoamine oxidase A. It is well known that serotonin active drugs, in combination with monoamine oxidase inhibitors can produce profound serotonin syndrome. To date, cases of serotonin syndrome, which resulted from concurrent methylene blue and serotonin active agents, have been published in the anesthesia literature. We report the first known case of serotonin syndrome in a patient receiving methylene blue for IIE. Show less

Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer major advantages over existing agents. The onset of the anticoagulant effect of these agents is rapid. Each agent has a predictable anticoagulant response that eliminates the need for monitoring. Clinical trials have been completed with all three agents in the prevention and treatment of the three leading causes of cardiovascular death: myocardial infarction, stroke, and venous thromboembolism (VTE). Novel agents… Show more

Dabigatran, rivaroxaban, and apixaban are novel oral anticoagulants that offer major advantages over existing agents. The onset of the anticoagulant effect of these agents is rapid. Each agent has a predictable anticoagulant response that eliminates the need for monitoring. Clinical trials have been completed with all three agents in the prevention and treatment of the three leading causes of cardiovascular death: myocardial infarction, stroke, and venous thromboembolism (VTE). Novel agents have shown reduced or similar rates of thrombosis, major bleeding, and adverse events when weighed against either low molecular weight heparin or warfarin. Additional trials are underway and more agents are in development. As a result, novel anticoagulants may impact physician prescribing practices and warrant consideration in patients requiring thrombosis management. Show less

Background: Digoxin has been reported to improve symptoms and reduce hospitalization in patients with heart failure as well as to control rapid ventricular rate in patients with atrial fibrillation. Both of these are high-prevalence diseases in the elderly, and yet studies have indicated that digoxin may not be used appropriately in this population. Clinical trials evaluating digoxin use specifically in the elderly are scarce.Objective: This article discusses the evidence on the therapeutic… Show more

Background: Digoxin has been reported to improve symptoms and reduce hospitalization in patients with heart failure as well as to control rapid ventricular rate in patients with atrial fibrillation. Both of these are high-prevalence diseases in the elderly, and yet studies have indicated that digoxin may not be used appropriately in this population. Clinical trials evaluating digoxin use specifically in the elderly are scarce.Objective: This article discusses the evidence on the therapeutic use of digoxin in the elderly and the changes in the pharmacokinetics of digoxin with aging to provide recommendations about the appropriate use of this drug in this population.Methods: Peer-reviewed clinical trials, review articles, and relevant treatment guidelines limited to those evaluating patients aged >65 years were identified from MEDLINE and the Current Contents database (both from 1966 to May 1, 2010) using the search terms digoxin, pharmacokinetics, heart failure, and atrial fibrillation. Citations from available articles were also reviewed for additional references.Conclusions: The elderly population appears to gain comparable benefits as does a younger population from the use of digoxin for heart failure management in terms of symptom improvement and reduction of hospitalization. In atrial fibrillation, digoxin does not control the ventricular rate as efficaciously during exercise and in high adrenergic states as do beta-blockers and calcium channel blockers. The elderly have reduced elimination of digoxin, so if digoxin is to be used, the dosing strategy must be conservative and therapeutic monitoring is needed. Further clinical studies are needed to confirm the pharmacokinetic parameters of digoxin in elderly patients with heart failure and/or atrial fibrillation.
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This article reviews the role of vernakalant in the management of atrial fibrillation (AF). Published data in English language were identified from MEDLINE and Current Content database (both 1966 to January 30, 2009). Vernakalant is an antiarrhythmic agent with sodium and ultra-rapid potassium channel blockage property and atrial selective effect. In clinical studies evaluating intravenous vernakalant in cardioversion of patients with recent onset AF, vernakalant improve the chance of acute… Show more

This article reviews the role of vernakalant in the management of atrial fibrillation (AF). Published data in English language were identified from MEDLINE and Current Content database (both 1966 to January 30, 2009). Vernakalant is an antiarrhythmic agent with sodium and ultra-rapid potassium channel blockage property and atrial selective effect. In clinical studies evaluating intravenous vernakalant in cardioversion of patients with recent onset AF, vernakalant improve the chance of acute restoration to normal sinus rhythm (NSR). In post-operative AF, the chance of conversion to NSR was also improved. Phase II studies demonstrated that oral vernakalant 300 mg or 600 mg twice daily successfully maintained normal sinus rhythm compared to placebo. Common side effects include dysgeusia, sneezing, and paresthesia. Future studies are needed to explore the efficacy and safety of using vernakalant with patient populations who are prone to AF, as well as its comparative efficacy and safety to other antiarrhythmic agents.
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