Observed Apixaban Anti-Xa Levels in Obese Patients.

BACKGROUND: Recent guidelines suggest that, for venous thromboembolism (VTE), standard doses of apixaban are appropriate in patients with body mass index (BMI) >40 kg/m2 or >120 kg. Atrial fibrillation (AF) is excluded from this recommendation. OBJECTIVE: The goals of our study were to measure and describe anti-Xa levels of patients with a BMI ≥40 kg/m2 and/or a weight ≥120 kg with a clinical indication of AF or VTE who were treated with apixaban, and to determine whether BMI or weight are associated with anti-Xa levels in this population. METHODS: We conducted an observational cohort study at a single health care system in Oregon, USA. Patients meeting enrollment criteria were recruited and had peak and trough apixaban anti-Xa levels drawn. RESULTS: Of 55 patients enrolled, 5 (9%) had peak anti-Xa levels below the reference range and 3 (6%) had trough anti-Xa levels below the reference range. BMI did not significantly correlate with peak or trough anti-Xa levels (r = -0.10, p = 0.45 and r = -0.14, p = 0.31). Weight had a moderate, negative correlation with peak anti-Xa levels (r = -0.42, p = 0.002) and a weak, negative correlation with trough anti-Xa levels (r = -0.32, p = 0.02). CONCLUSIONS AND RELEVANCE: This study provides evidence that anti-Xa levels among obese patients are not substantially different from patients with nomral BMI and weight. This supports recent ISTH guidance for standard dosing of apixaban for VTE patients with BMI >40 kg/m2 or weight >120 kg and provides additional evidence that the standard dosing may also be appropriate in patients with AF.

Perioperative supplementation of polyunsaturated omega-3 fatty acid for the prevention of atrial fibrillation after cardiothoracic surgery.

PURPOSE: The effect of perioperative supplementation of polyunsaturated omega-3 fatty acid (PUFA) on the frequency of atrial fibrillation (AF) in patients without a history of AF was evaluated. METHODS: A total of 561 patients were randomized to receive either 1 g of PUFA or placebo twice daily. Treatment was started up to five days before surgery or within 24 hours after surgery, depending on when consent was received. Treatment was continued until the patient's follow-up visit with the cardiologist up to four weeks after surgery. The primary endpoint of the study was AF before hospital discharge. Secondary endpoints included AF within one week after surgery, AF within one month after surgery, length of hospital stay, postoperative bleeding complications, and readmission within one month after surgery. RESULTS: No significant reduction in the risk of AF was observed at hospital discharge (relative risk [RR], 0.98; p = 0.922) or at three weeks after surgery (RR, 0.98; p = 0.844). After restricting the analysis to treatment-adherent patients, the association remained nonsignificant at hospital discharge (RR, 0.90; p = 0.374) and at three weeks after surgery (RR, 0.90; p = 0.330). No significant differences were observed between treatments for rates of readmission, death, and bleeding complications or the length of hospital stay. CONCLUSION: Perioperative supplementation with PUFA did not decrease the risk of AF in the immediate postoperative period. PUFA also had no effect on the length of hospital stay, postoperative bleeding complications, and readmissions within one month after surgery.

Quantitation of mercapturic acid conjugates of 4-hydroxy-2-nonenal and 4-oxo-2-nonenal metabolites in a smoking cessation study.

The breakdown of polyunsaturated fatty acids (PUFAs) under conditions of oxidative stress results in the formation of lipid peroxidation (LPO) products. These LPO products such as 4-hydroxy-2-nonenal (HNE) and 4-oxo-2-nonenal (ONE) can contribute to the development of cardiovascular and neurodegenerative diseases and cancer. Conjugation with glutathione, followed by further metabolism to mercapturic acid (MA) conjugates, can mitigate the effects of these LPO products in disease development by facilitating their excretion from the body. We have developed a quantitative method to simultaneously assess levels of 4-oxo-2-nonen-1-ol (ONO)-MA, HNE-MA, and 1,4-dihydroxy-2-nonene (DHN)-MA in human urine samples utilizing isotope-dilution mass spectrometry. We are also able to detect 4-hydroxy-2-nonenoic acid (HNA)-MA, 4-hydroxy-2-nonenoic acid lactone (HNAL)-MA, and 4-oxo-2-nonenoic acid (ONA)-MA with this method. The detection of ONO-MA and ONA-MA in humans is significant because it demonstrates that HNE/ONE branching occurs in the breakdown of PUFAs and suggests that ONO may contribute to the harmful effects currently associated with HNE. We were able to show significant decreases in HNE-MA, DHN-MA, and total LPO-MA in a group of seven smokers upon smoking cessation. These data demonstrate the value of HNE and ONE metabolites as in vivo markers of oxidative stress.

Effects of vitamin E on cholesterol levels of hypercholesterolemic patients receiving statins.

PURPOSE: The effects of vitamin E supplementation on the cholesterol levels of hypercholesterolemic patients receiving statin therapy were studied. METHODS: In this prospective, single-blind, placebo-controlled, randomized trial, patients who were currently taking either lovastatin or simvastatin for a primary diagnosis of hypercholesterolemia were given placebo for two weeks and then randomized to receive a supplement of either 400 IU of vitamin E or matching placebo after dinner for eight weeks, followed by a two-week washout period. RESULTS: Vitamin E supplementation increased plasma alpha-tocopherol concentrations approximately 1.6-fold and increased excretion of its urinary metabolite 4-fold significantly from week 2 to week 6 (p < 0.001 for both comparisons). During the eight-week supplementation period, no statistically significant differences in any lipoprotein cholesterol fraction were detected between groups; however, a 6% decrease in high-density-lipoprotein (HDL) cholesterol was detected within the vitamin E group from week 2 to week 6 (p < 0.05), but the decrease was not sufficient to change the cardiac risk ratio. Neither cytochrome P-450 isoenzyme (CYP) 3A (as measured by hydroxylation of urinary cortisol) nor cholesteryl ester transfer protein (CETP) activity was significantly altered during the study. CONCLUSION: Vitamin E supplementation did not affect total or low-density-lipoprotein cholesterol levels in hypercholesterolemic patients receiving lovastatin or simvastatin. A small but significant decrease in HDL cholesterol levels was observed in the group that received vitamin E supplementation during the supplementation period, but this decrease was no longer significantly different from the placebo group's levels two weeks postsupplementation. The decrease in HDL cholesterol levels did not appear to be related to either CYP3A or CETP.

Memory loss in a patient treated with fluoxetine.

OBJECTIVE: To report a case of severe memory loss in an elderly patient after initiation of fluoxetine. CASE SUMMARY: An 87-year-old white woman was started on fluoxetine for depression, and the dose was titrated to 20 mg/d. She developed progressive memory loss over the next 6 weeks for which she ultimately was hospitalized. Other potential causes for her memory loss were ruled out. After fluoxetine was discontinued, the patient's memory improved significantly over the next 2 months. An objective causality assessment indicated a possible relationship between the memory loss and fluoxetine in this patient. DISCUSSION: Our report documents a case of severe reversible memory deterioration after initiating fluoxetine. Fluoxetine has a favorable adverse effect profile when compared with older classes of antidepressants. Postmarketing studies and isolated case reports, however, suggest that fluoxetine may harm memory in some patients. Some selective serotonin-reuptake inhibitors (SSRIs) appear to cause memory loss more frequently than others. CONCLUSIONS: Clinicians should be aware of the possible effects of fluoxetine (and possibly other SSRIs) on memory.

Blood pressure elevation in a patient treated with salsalate.

OBJECTIVE: To report a case of increased blood pressure associated with the use of salsalate in an elderly patient with no prior history of hypertension. CASE SUMMARY: A 78-year-old white man with no prior history of hypertension initiated salsalate therapy for low-back pain. Over the 15 months prior to the initiation of salsalate, his blood pressure averaged 127 +/- 7 mm Hg systolic and 84 +/- 6 mm Hg diastolic (mean +/- SD). After initiation of salsalate, he experienced significant elevations in blood pressure, which led to a preliminary diagnosis of hypertension. Blood pressure after initiation of salsalate averaged 150 +/- 13 mm Hg systolic and 95 +/- 5 mm Hg diastolic. No changes in medications or medication doses (with the exception of warfarin) occurred in the 18 months prior to or during salsalate therapy. His weight remained stable. A detailed review of his medical records and history revealed no other causes for these elevations in blood pressure. Salsalate therapy was discontinued and his blood pressure returned to normotensive levels (119 +/- 2 mm Hg systolic and 81 +/- 2 mm Hg diastolic). DISCUSSION: Nonsteroidal antiinflammatory drug (NSAID)-induced elevations in blood pressure have been well documented in patients receiving antihypertensive medications. Due to its relative weak inhibition of cyclooxygenase and lack of published literature in hypertensive patients, salsalate is considered to have little or no effect on blood pressure. Our report documents a possible case of salsalate-induced hypertension in a previously normotensive elderly man. Observational studies suggest that NSAID use may increase the risk of developing hypertension in older patients. CONCLUSIONS: Clinicians should be aware of the possible effects of NSAIDs on blood pressure. Blood pressure monitoring following the initiation of salsalate may be warranted, particularly in older patients.

Asthma and gastroesophageal reflux.

Gastroesophageal reflux and asthma are common diseases in the developed world, and they often coexist in patients. Animal experiments, epidemiologic data, and clinical studies suggest that gastroesophageal reflux may contribute to the pathogenesis of asthma. In addition to classic reflux symptoms, such patients may notice nightly exacerbations of asthma or postprandial worsening of their pulmonary symptoms. Empiric treatment with an acid-suppressive regimen is the most cost-effective approach for asthmatic patients with classic gastroesophageal reflux symptoms, especially if the asthma remains poorly controlled despite conventional treatment. If patients have persistent problems after an adequate duration of acid-suppressive therapy or if they report symptoms indicating complicated reflux disease, such as dysphagia, additional diagnostic studies should be initiated. In most cases, medical therapy should be chosen for the long-term treatment of patients with asthma and gastroesophageal reflux. With the availability of less-invasive laparoscopic surgery, fundoplication may be an alternative in selected, mostly young individuals who have documented reflux and symptoms responsive to appropriate acid-suppressive regimens.