Evaluation of Time to Therapeutic Anticoagulation and Associated Outcomes in Critically Ill, Obese Patients With Pulmonary Embolism Receiving Unfractionated Heparin.

BACKGROUND: Delays in time to therapeutic activated partial thromboplastin time (aPTT) have been associated with poor outcomes in patients with acute pulmonary embolism (PE). OBJECTIVE: To investigate the relationship between time to therapeutic anticoagulation and in-hospital mortality in critically ill, obese patients with acute PE. METHODS: This study examined 204 critically ill patients with a body mass index (BMI) ≥30 kg/m2 receiving unfractionated heparin (UFH) for PE treatment. Patients achieving therapeutic anticoagulation within 24 hours of UFH initiation (early) were compared to those in >24 hours (delayed). Additional end points included 30-day mortality, median time to therapeutic aPTT, proportion of therapeutic and supratherapeutic aPTT values, hemodynamic deterioration, thrombolytic therapy after UFH initiation, length of stay, and bleeding. RESULTS: No difference in in-hospital or 30-day all-cause mortality was seen (odds ratio [OR]: 1.33, confidence interval [CI]: 0.647-2.72; OR: 1.003, CI: 0.514-1.96). Patients in the early group had a greater proportion of therapeutic aPTT values (66.7% vs 50%, P < .001) and higher percentage of supratherapeutic aPTT values (20.9% vs 11.3%, P < .001); however, no increase in clinically significant bleeding was evident (15.2% vs 10.9%, P = .366). CONCLUSION: In this population, a shorter time to therapeutic aPTT was not associated with improved survival.

Assessment of bleeding events associated with short-duration therapeutic enoxaparin use in the morbidly obese.

BACKGROUND: Enoxaparin dosing for patients with morbid obesity is uncertain, and therefore, an elevated incidence of bleeding may exist in this group. OBJECTIVE: To determine if increased bleeding events occur in patients with morbid obesity (body mass index ≥ 40 kg/m(2)) compared with lower-weight patients with treatment doses of enoxaparin. METHODS: Patients at a single, academic medical center receiving enoxaparin for at least 24 hours from July to December 2009 were retrospectively evaluated. Patients with morbid obesity were randomly selected among the total cohort and were matched with lower-weight controls (1:2 ratio) based on the presence of renal dysfunction (serum creatinine >1.4 mg/dL). Bleeding events, defined on the basis of laboratory changes, administration of blood products, or clinical data, occurring up to 24 hours after enoxaparin administration were evaluated. Independent risk factors for bleeding were assessed via multivariate analysis. RESULTS: The maximum single dose administered throughout the study was 150 mg, and the largest patient enrolled weighed 175 kg. Final enoxaparin doses in morbidly obese (0.98 mg/kg) patients were lower compared with that in controls (1.04 mg/kg, P < .01). The proportion of patients with bleeding events was 29% in the morbidly obese and 23.5% in the control group (P = .30). Enoxaparin doses <0.9 mg/kg (adjusted odds ratio [AOR] = 2.35; 95% CI = 1.01-5.47; P = .04), durations of therapy beyond 48 hours (AOR = 2.42; 95% CI = 1.35-4.33; P < .01), and female gender (AOR = 2.05; 95% CI = 1.12-3.73; P = .02) were associated with bleeding, whereas warfarin use (AOR = 0.46; 95% CI = 0.26-0.81; P < .01) was associated with fewer bleeding events. CONCLUSIONS: Results suggest that dosing enoxaparin in morbidly obese patients (up to 175 kg in weight) with doses capped at 150 mg was not associated with increased bleeding incidence.

Role of new drugs for management of atrial fibrillation.

OBJECTIVE: To evaluate the role of newer agents in the management of atrial fibrillation (AF). DATA SOURCES: EMBASE and MEDLINE were searched (up to June 2012) combining medication names with atrial fibrillation, humans, clinical trials, and pharmacoeconomic. References of the articles identified and www.clinicaltrials.gov were also reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies were limited to the English language with clinical or pharmacoeconomic end points followed by the consensus of 3 authors. DATA SYNTHESIS: Formulated to reduce some of the adverse effects associated with amiodarone by removing the iodine component, dronedarone has improved clinical outcomes over placebo when used in paroxysmal or persistent AF; however, it is less efficacious than amiodarone. Worse outcomes with dronedarone have been seen in patients with heart failure or permanent AF. It has not been compared to antiarrhythmic agents other than amiodarone, and pharmacoeconomic evaluations are lacking. Dabigatran 150 mg is superior to warfarin in preventing stroke or systemic embolism and has been associated with lower rates of vascular-associated mortality. Although the rates of major bleeding were not significantly different between the 2 agents, gastrointestinal bleeding and myocardial infarction occurred more frequently with dabigatran. Dabigatran appears to have the most pharmacoeconomic benefit over warfarin in patients with a higher risk of stroke. Rivaroxaban is noninferior to warfarin for the prevention of stroke and systemic embolism, with no difference in the rates of major bleeding. Cost-effectiveness studies have not been performed with this agent at this time. In patients with AF who were not suitable candidates for warfarin, apixaban is superior to aspirin in preventing stroke or systemic embolism without increasing the risk for major bleeding. Additionally, apixaban is superior to warfarin in preventing stroke or systemic embolism, results in fewer bleeding events, and is associated with lower mortality. Apixaban is not cost-effective against aspirin when used for a short duration but gains superiority with prolonged use or in patients with higher risks of stroke. Additionally, apixaban appears to offer a pharmacoeconomic advantage over warfarin at no to minimal cost. Each new anticoagulant lacks a reversal agent and an assay to detect the presence of the anticoagulant, as well as long-term data when used in the clinical setting. CONCLUSIONS: Use of dronedarone should be limited to patients with paroxysmal or persistent AF and should not be used in patients with heart failure or with permanent AF. Newer antithrombotic agents appear to be promising alternatives for the prevention of stroke in patients with AF; however, more data are needed to understand their role.

Evaluation of therapeutic anticoagulation with enoxaparin and associated anti-Xa monitoring in patients with morbid obesity: a case series.

Our purpose was to describe anti-Xa levels, dosage requirements, and complications associated with enoxaparin treatment doses in patients with morbid obesity. Inpatients with a BMI >40 kg/m(2) at an academic medical center prescribed therapeutic enoxaparin from 2004 to 2010 who also had an associated anti-Xa level were included in this retrospective evaluation. Twenty-six patients were identified having median weight of 162 kg (range 106-243), median BMI of 49.5 kg/m(2) (range 40.1-98.1), and median enoxaparin duration of 4 days (range 1-32). Venous thromboembolism was the most common reason for anticoagulation (n = 19, 73%). The median starting dose was 0.8 mg/kg actual body weight (range 0.51-1; absolute dose 80-150 mg) every 12 h. Twelve patients (46%) achieved a goal anti-Xa level, 10 (38%) were above goal and 4 (15%) were uninterpretable. Among the 10 patients with anti-Xa levels above goal, the median initial dose was 0.85 mg/kg (range 0.75-1) versus 0.74 mg/kg (range 0.51-1) for patients at goal with similar median peak serum creatinine (PSCr) values between these two groups (P > 0.05). No bleeding events occurred in patients achieving goal anticoagulation versus 4/10 (40%) with high anti-Xa levels (P = 0.033) with similar median PSCr between these groups. No thrombotic events occurred while on therapy. The majority in this cohort with morbid obesity achieved anti-Xa levels at or above goal at doses less than the recommended 1 mg/kg every 12 h. Bleeding events were more frequent among patients with anti-Xa levels above goal, despite similar PSCr values.

Identifying optimal initial infusion rates for unfractionated heparin in morbidly obese patients.

BACKGROUND: Most literature available for unfractionated heparin (UFH) supports the use of actual body weight for dosing all patients, yet a small proportion of the patients in these studies were morbidly obese. The most appropriate dosing strategy for therapeutic UFH in this patient population is not clearly defined. OBJECTIVE: To better define appropriate UFH dosing strategies in morbidly obese patients and to evaluate the safety of a weight-based heparin nomogram in this patient population. METHODS: Patients with class III (morbid) obesity receiving therapeutic doses of a UFH infusion for greater than 24 hours were evaluated. Two comparator groups of overweight/class I -II obesity and normal/underweight patients were created by matching patients to the class III obesity group. Doses and times to therapeutic activated partial thromboplastin time (aPTT), bleeding rates, and mortality were assessed. RESULTS: The mean infusion rate required to obtain a first therapeutic aPTT was 11.5 units/kg/h in the class III obesity group (n = 94) versus 12.5 units/kg/h and 13.5 units/kg/h for the overweight/class I-II obesity (n = 92) and normal/underweight (n = 87) groups, respectively (p = 0.001). The mean times to a first therapeutic aPTT were 21.3, 22.1, and 29.9 hours, respectively (p = 0.421). There was a statistically significant difference in the infusion rate required to obtain 2 consecutive therapeutic aPTTs between groups (p = 0.016), with higher weight groups requiring smaller (per kilogram actual body weight) infusion rates, but there was no significant difference in the time to reach 2 consecutive therapeutic aPTTs (p = 0.776). There was no significant difference in bleeding (p = 0.517) or mortality (p = 0.475) among groups. CONCLUSIONS: Morbidly obese patients require smaller UFH infusion rates per kilogram actual body weight compared to patients with lower body mass indices. UFH dosing recommendations should be modified to reflect body mass index classification.