Direct Oral Anticoagulants and Concomitant Anti-seizure Medications: A Retrospective, Case-Control Study in a Real-World Setting.

PURPOSE: Although prescription of direct oral anticoagulants (DOACs) for epileptic patients on anti-seizure medications (ASMs) is on the increase, international guidelines pose strict restrictions because this may lead to pharmacologic interactions. However, current evidence on their clinical relevance remains scanty. This retrospective, case-control study assessed the frequency of ischemic/hemorrhagic events and epileptic seizures involving DOAC-ASM cotherapy in the real world, compared with DOAC and ASM monotherapy, in age- and gender-matched controls. METHODS: Data on patients who had been prescribed a concomitant DOAC and ASM therapy for at least 6 months were extracted from the database of the Pharmaceutical Service of the Alessandria Province (Italy). After exclusions, the case group included 124 patients, 44 on valproic acid (VPA) and 80 on levetiracetam (LEV) concomitant with a DOAC, and it was compared with the DOAC-control and ASM-control groups. The clinical and laboratory data were extracted from the electronic archives of the hospitals in the same province. FINDINGS: Two (1.6%) ischemic and 2 (1.6%) major hemorrhagic events were observed in the case group. Four (3.2%) ischemic and no hemorrhagic events occurred in the DOAC-control group. There were no statistically significant differences in the ischemic and hemorrhagic events between the case group (patients on concomitant LEV or VPA who were prescribed a DOAC) and the DOAC-control group, and there was no difference in the recurrence rate of epileptic seizures between the case group and the ASM-control group. IMPLICATIONS: Although this study has some limits, mainly the small sample size, our findings indicate that neither LEV nor VPA concomitant treatment significantly affects the effects of DOACs in a real-world setting.

Successful intravenous thrombolysis for ischemic stroke after reversal of dabigatran anticoagulation with idarucizumab: a case report.

BACKGROUND: Non-vitamin K antagonist oral anticoagulants, including dabigatran, are currently widely used for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation. Recently, idarucizumab, a monoclonal antibody fragment for immediate reversal of dabigatran-induced anticoagulation, has been introduced into the market to be used in life-threatening bleeding or urgent surgery, allowing for rapid normalization of clotting parameters. The use of idarucizumab is not yet well established in patients presenting with acute ischemic stroke on dabigatran who are candidates for thrombolytic therapy. CASE PRESENTATION: We report the case of a 71-year-old hypertensive Caucasian woman with non-valvular atrial fibrillation treated with dabigatran 150 mg twice daily, who presented with acute ischemic stroke causing right-sided hemiparesis and aphasia. Two hours after presentation to the emergency department, a decision was made to administer idarucizumab for achieving complete reversal of any potential anticoagulant effect of dabigatran and, in the absence of any contraindications, our patient underwent successful thrombolysis. At discharge, our patient was able to walk unassisted and had only residual aphasia. Twenty days later, she had completely recovered motor function of her right side, with further progressive improvement of aphasia. Repeat cranial computed tomography confirmed the absence of hemorrhage, and anticoagulant therapy with dabigatran 150 mg twice daily was resumed. CONCLUSIONS: Our case report adds to the evidence that idarucizumab administration is safe in the setting of patients with atrial fibrillation treated with dabigatran who develop acute ischemic stroke requiring thrombolysis.

A case report of parenchymal hematoma after intravenous thrombolysis in a rivaroxaban-treated patient: Is it a true rivaroxaban hemorrhagic complication?

RATIONALE: To date, the only treatment approved for acute ischemic strokes is thrombolysis. Whether intravenous thrombolysis may be safe in patients taking direct oral anticoagulants (DOACs) is currently a matter of debate. PATIENT CONCERNS: A 74-year-old woman, who was on rivaroxaban 20 mg/d for nonvalvular atrial fibrillation, was admitted to our stroke unit with left-sided hemiparesis and aphasia. The onset of neurologic deficits had occurred 5 hours after the last rivaroxaban dose. DIAGNOSIS: An acute ischemic stroke was diagnosed. INTERVENTIONS: The patient was administered thrombolytic treatment with intravenous recombinant tissue plasminogen activator (r-TPA) 3 hours and 20 minutes after symptoms onset. Seven hours post-r-TPA treatment, the neurological deficit had worsened, and a type I intraparenchymal hematoma was detected on a computed tomography brain scan. OUTCOMES: The clinical/neuroradiological picture improved significantly in the following days. The patient was discharged to a rehabilitation facility after 3 weeks. LESSONS: In this case, factor ten activated (Xa) inhibitor, rivaroxaban might have increased the risk of hemorrhagic transformation of the ischemic stroke. However, this risk was overweighed by the benefit of thrombolysis, as the patient's clinical condition had improved significantly in the following weeks. The current guidelines discourage the use of thrombolytic treatment in patients with DOACs administered within the last 24(48) hours. However, the case reported herein and other world experiences, even though limited, suggest that an ongoing DOAC medication could no longer be considered a barrier to r-TPA treatment which may be a reasonable and valuable option, at least in selected acute stroke patients taking factor Xa inhibitors.

One-year GH replacement therapy reduces early cardiac target organ damage (TOD) in adult GHD patients.

Hypopituitarism reduces life expectancy and increases the risk of cardiovascular and cerebrovascular diseases, as well as death. Abnormalities in the cardiovascular system may be independently related to GH deficiency (GHD). The aim of this study was to prospectively investigate coronary flow reserve and diastolic function in GHD adult patients at diagnosis and after 1 year of GH replacement therapy. As control group, an age- and sex-matched population was chosen. All patients and controls were non-smokers, non-diabetic, and normotensive, with no history of vascular disease. 14 patients with adult-onset GHD and 17 controls represent the two study groups. Anthropometric data, blood pressure, lipid profile, glycosylated hemoglobin (HbA1c) and IGF-I plasma levels, coronary flow reserve (CFR), and LV diastolic function (evaluated by E/A) were collected in all subjects before and after 12 months of GH replacement therapy. Compared with controls, systolic and diastolic blood pressure and LDL cholesterol levels were significantly higher at baseline and return, comparable to controls after 1 year of GH replacement (GHRT). GHD patients showed a blunted CFR at baseline (P < 0.001) and a significant improvement after GHRT, returning to values comparable with those recorded in the control group. In addition, after therapy a significant (P < 0.001) improvement in E/A was recorded. One year of GH therapy improves CFR and E/A in the patient population analyzed, thereby encouraging the early start of GHRT.

Citalopram and levosulpiride: a dangerous drug combination for QT prolongation.

We report the case of an 89-year-old female patient who presented to the emergency department after out-of-hospital cardiac arrest due to polymorphic ventricular tachycardia treated by public access defibrillation. The admission electrocardiogram (ECG) showed extreme QT prolongation (650 milliseconds) with recurrent episodes of nonsustained polymorphic ventricular tachycardia. Intravenous magnesium sulfate therapy was instituted. After history taking, it was found that the patient was on citalopram and that, 2 days prior to admission, she had begun treatment with levosulpiride. This drug combination resulted in marked prolongation of the QT interval that triggered the electrical storm.

Biventricular Pacemaker Implantation via the Femoral Vein.

We report the case of biventricular pacemaker implantation via the femoral vein, in a patient with impossibility of using standard superior vein approach and a contraindication to epicardial lead placement.

A dangerous fruit juice.

We report the case of a female patient presenting to the emergency department with postprandial syncope and atrial fibrillation. After amiodarone administration, the electrocardiogram showed marked QT prolongation associated with ventricular arrhythmias, including an episode of torsade de pointes requiring immediate electrical cardioversion. During history taking, the patient reported that she had been drinking large amounts of grapefruit juice regularly. The inhibition of amiodarone metabolism induced by grapefruit juice was responsible for enhancing the proarrhythmic effects of the drug with development of electrical storm.

[Atrial myxoma presenting during pregnancy]. / Riscontro di mixoma atriale in corso di gravidanza.

We report a case of left atrial myxoma presenting as acute respiratory failure following surgical intervention for voluntary interruption of pregnancy. After cardiac surgery T-wave changes were observed on the ECG, most likely due to coronary embolism.

Coronary flow reserve is impaired in hypertensive patients with subclinical renal damage.

BACKGROUND: Renal dysfunction is relatively common in patients with primary hypertension (PH). A reduction in coronary vasodilator capacity has recently been reported in patients with renal damage undergoing coronary angiography. We investigated the relationship between coronary flow reserve (CFR) and early renal abnormalities in patients with PH and normal serum creatinine. METHODS: Seventy-six untreated patients were studied. Albuminuria was measured as the albumin-to-creatinine ratio and glomerular filtration rate (eGFR) was estimated by the Cockroft-Gault formula. Chronic kidney disease (CKD) was defined as an eGFR <60 ml/min/1.73 m(2) and/or in the presence of microalbuminuria. Coronary blood flow velocities (cm/s) were measured by Doppler ultrasound at rest and after adenosine administration. CFR was defined as the ratio of hyperemic-to-resting diastolic peak velocities. RESULTS: Prevalence of reduced eGFR, microalbuminuria, CKD, and left ventricular (LV) hypertrophy was 8, 10, 16, and 31%, respectively. Overall, 10% of patients showed impaired CFR (i.e., <2.0). Patients with CKD were more likely to be older (P < 0.05) and of female gender (P < 0.01) and showed higher LV mass index (LVMI) (P < 0.05), lower CFR (P < 0.05; analysis of covariance, P < 0.05), and CFR/LVMI (P < 0.05) than patients with normal renal function. Conversely, patients with impaired CFR showed a significantly higher prevalence of reduced eGFR (chi(2) 5.2, P < 0.05), microalbuminuria (chi(2) 10.2, P < 0.01), and CKD (chi(2) 9.2.1, P < 0.01). Even after adjustment for gender, the presence of CKD entailed a sevenfold higher risk of having impaired CFR (confidence interval 1.17-40.9, P < 0.05). CONCLUSION: Early renal abnormalities are associated with reduced CFR in PH.