Ropinirole-Associated Orthostatic Hypotension as Cause of a Prescribing Cascade in an Elderly Man.

Ropinirole is an overall well-tolerated antiparkinsonian medication that is also used to treat restless leg syndrome (RLS). The incidence of side effects is low, with orthostatic hypotension (OH) only anecdotally reported. Additionally, it is known that the elderly population is very susceptible to adverse drug effects and the prevalence of prescribing cascades that these can trigger is unknown. A 71-year-old male with history of atrial fibrillation, well-controlled diabetes on oral agents, hyperlipidemia, hypertension, ischemic heart failure status post (s/p) implantable cardioverter-defibrillator (ICD) placement with improved ejection fraction (EF), transient ischemic attack (TIA), rheumatoid arthritis, RLS, aortic stenosis s/p mechanical aortic valve replacement on anticoagulation, deep venous thrombosis (DVT), and right knee replacement, presented to the ED with generalized weakness, with difficulty standing from seated position, followed by a fall without head trauma. Over the eight months prior to this presentation, the patient had had similar symptoms that resulted in four falls, two hospital admissions, and new prescriptions of midodrine and compression stockings. On admission, vital signs were remarkable for positive orthostatics with blood pressure (BP) 110/74 mmHg, heart rate (HR) of 86 bpm in supine position and BP 87/51 mmHg, HR of 70 bpm while in standing position. Physical exam was unremarkable except for a known ejection murmur and dry oral mucous membranes. Labs included a creatinine 3.6 mg/dl, blood urea nitrogen (BUN) 66 mg/dl, international normalized ration (INR) of 4.1, B-natriuretic peptide (BNP) of 313 pg/mL, troponin <0.03 ng/mL. A kidney ultrasound was normal, and a transthoracic echocardiogram showed left ventricle ejection fraction (LVEF) of 55-65%, improved compared to a prior study. Furosemide, carvedilol and canagliflozin were discontinued and IV fluids were administered. In the subsequent days, his creatinine improved, and so did the patient's volume status, but he continued to be orthostatic despite midodrine and stockings. On further interview, the patient disclosed starting ropinirole 0.25 mg three times daily approximately 10 months prior to this admission, due to asymptomatic RLS that was reported in a sleep study. Decision was made to discontinue this medication, which resulted in improvement of symptoms. We were able to discontinue IV fluids, midodrine and stockings, and reintroduce carvedilol, furosemide and canagliflozin in a stepwise manner. In a follow-up visit one month after discharge, the patient was symptom-free. This case illustrates two major points. First, this prescribing cascade potentially induced by ropinirole, as well as the increase in health care costs associated to iatrogenic admissions, is major preventable problem faced mostly by the geriatric population. Second, although OH associated with ropinirole has only been reported in patients treated for Parkinson's disease, this side effect should be considered when prescribing ropinirole for other indications, with cautious assessment of risks and benefits. Further studies need to be conducted to establish the frequency of OH related to ropinirole.

Rendimiento de ecuaciones para predecir riesgo cardiovascular en una población de Argentina / Performance of equations to predict cardiovascular risk in an Argentine population

Resumen El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la saludregión América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Abstract The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health OrganizationAmerican B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

[Performance of equations to predict cardiovascular risk in an Argentine population]. / Rendimiento de ecuaciones para predecir riesgo cardiovascular en una población argentina.

The performance of available risk scores to predict cardiovascular risk (CVR) in the Argentinian population is unknown. Our aim was to compare the CVR predicted by several equations with the occurrence of cardiovascular events (CVE) in patients without known cardiovascular disease in an Argentinian hospital. Adults between 40 and 70 years were randomly selected, excluding those with prior history of major CVE, active cancer, lipid lowering treatment and absence of follow-up data. Framingham 2008, SCORE (low and high-risk populations), ATP III, World Health Organization- American B region (WHO-B) and Pooled Cohort equations (PC) risk scores were used to calculate 10-y CVR at time of enrollment. End of follow-up was 10 years ± 6 months, occurrence of fatal myocardial infarction or death from any cause. We used ROC curves to assess discrimination (AUC > 0.75 good discrimination), and Hosmer Lemeshow chi-square to evaluate calibration (Chi > 20 or p value < 0.05 poor calibration). We included 606 patients in our study, 336 women, average age 56.7 ± 8.4 year. Of those, 10 (1.7%) non-cardiovascular deaths, and 5 (0.8%) cardiovascular deaths were observed. 58 (9.8%) a non-fatal CVE were recorded. There was acceptable discrimination for Framingham, ATP-III, and both PC equations. The global calibration was only good with the ATP-III and PC equations. The observed frequency of CVE was low, and the CVR was overestimated by all equations. However, applying ATP-III or PC equations to assess CVR could be considered in our population.

El rendimiento de las ecuaciones existentes de predicción de riesgo cardiovascular (RCV) en población argentina es desconocido. Se comparó RCV estimado por dichas ecuaciones, con la ocurrencia de eventos cardiovasculares (ECV) en una población de pacientes sin enfermedad cardiovascular de un hospital argentino. Se incluyeron aleatoriamente adultos entre 40 y 70 años, excluyéndose quienes al momento del enrolamiento presentaban historia de ECV mayor, cáncer activo, o tratamiento hipolipemiante. Se calculó RCV a 10 años al momento de inclusión, utilizando ecuaciones de Framingham 2008, SCORE (para poblaciones de bajo y alto riesgo), ATP III, Organización mundial de la salud- región América B (OMS-B) y Ecuación de Cohorte Agrupada (ECA). El fin de seguimiento fue 10 años ± 6 meses, ocurrencia de infarto de miocardio fatal o muerte por cualquier causa. Se utilizaron curvas ROC para evaluar discriminación (ABC > 0.75 buena discriminación). La calibración se evaluó mediante chi-cuadrado de Hosmer Lemeshow (Chi > 20 o p < 0.05 pobre calibración). Incluimos 606 pacientes, 366 mujeres, edad promedio 56.7 ± 8.4 años. Se observaron 10 (1.7%) muertes de causa no cardiovascular, 5 (0.8%) causa cardiovascular. Se registraron 58 (9.8%) ECV no fatales. Hubo aceptable discriminación para ecuaciones de Framingham, ATP-III y ECA. La calibración global solo fue buena con las ecuaciones de ATP-III y ECA. La frecuencia observada de ECV fue baja, y hubo sobreestimación de RCV con todas las ecuaciones. Sin embargo, se podría sugerir la aplicación de las ecuaciones de ATP-III o ECA en esta población.

Decreased Rivaroxaban Levels in a Patient with Cerebral Vein Thrombosis Receiving Phenytoin.

Combined use of antiepileptic drugs and anticoagulants is common. We describe the first case documenting laboratory interaction between rivaroxaban and phenytoin. A 48-year-old woman was admitted to our hospital due to cerebral venous thrombosis, bilateral pulmonary embolism, and deep vein thrombosis. She came from a small town with difficult access to warfarin monitoring. She was receiving phenytoin 100 mg three times daily (t.i.d.) and started enoxaparin 60 mg twice daily (b.i.d.). An abdominal mass was diagnosed and removed by laparoscopy (gastrointestinal stromal tumor). On day 5, she was switched to rivaroxaban 15 mg b.i.d. First peak anti-Factor Xa was 70 ng/ml (reference value: 100-300 ng/ml). She was discharged on rivaroxaban 15 mg b.i.d. and phenytoin 100 mg t.i.d. A week later, anti-Xa levels were 90 ng/ml. Due to concerns about thrombosis progression, she was switched to dabigatran. During follow-up, she remained asymptomatic and thrombin time >180 s was measured several times along 3 months as surrogate for dabigatran activity. Phenytoin is a combined CYP3A4 and P-glycoprotein inducer, which might reduce rivaroxaban levels. Dabigatran is substrate of P-glycoprotein, meaning potential malabsorption. Despite unavailability of plasmatic dabigatran essays, our patient improved her symptoms without further symptomatic thromboembolism. Facing these interactions, either monitoring serum levels of anticoagulants or other therapeutic options should be considered.