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1.
Diagnosis and management of hyponatraemia in the older patient.
Woodward, M, Gonski, P, Grossmann, M, Obeid, J, Scholes, R, Topliss, DJ
Internal medicine journal. 2018;:5-12
Abstract
Hyponatraemia (serum sodium concentration below 135 mmol/L) is the most common electrolyte disturbance and occurs commonly in older people. The causes can be complex to diagnose and treat and many published guidelines do not focus on the issues in an older patient group. Here, we are principally concerned with diagnosis and management of euvolaemic and hypervolaemic hyponatraemia in hospitalised patients over 70 years old. We also aim to increase awareness of hyponatraemia in residential aged care facilities and the community. Hyponatraemia can have many causes; in older people, chronic hyponatraemia can often be the result of medications used to treat chronic disease, particularly thiazide or thiazide-like drugs (such as indapamide) or drugs acting on the central nervous system. Where a reversible trigger (such as drug-induced hyponatraemia) can be identified, hyponatraemia may be treated relatively simply. Chronic hyponatraemia due to an irreversible cause will require ongoing treatment. Fluid restriction can be an effective therapy in dilutional hyponatraemia, although poor compliance and the burdensome nature of the restrictions are important considerations. Tolvaptan is an oral vasopressin receptor antagonist that can increase serum sodium concentrations by increasing electrolyte-free water excretion. Tolvaptan use is supported by clinical trial evidence in patients with hypervolaemic or euvolaemic hyponatraemia below 125 mmol/L. Clinical trial evidence also supports its use after a trial of fluid restriction in patients with symptomatic hyponatraemia above 125 mmol/L. The use of tolvaptan is affected by regulatory restriction of chronic therapy due to safety concern and the non-subsidised cost of treatment.
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2.
Tolvaptan for Heart Failure in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis.
Sen, J, Chung, E, McGill, D
Heart, lung & circulation. 2018;(8):928-939
Abstract
BACKGROUND Heart failure (HF) is frequently associated with renal impairment. Tolvaptan is reported to be effective in treating congestion in HF without significant electrolyte loss compared to conventional diuretics. However, the safety and efficacy of its use in patients with chronic kidney disease (CKD) is uncertain. This systematic review and meta-analysis evaluated the efficacy and safety outcomes of tolvaptan for HF management in patients with CKD, with a focus at a physiologic basis related to safety. METHODS We searched for observational studies and randomised clinical trials (RCTs) that assessed the effects of tolvaptan against placebo or standard care in adult patients with HF and CKD. Our protocol was registered with PROSPERO (number CRD42017052775). RESULTS Seventeen studies were included in the qualitative review and six in the meta-analysis involving 1597 patients. Tolvaptan was associated with an increase in sodium concentration. No significant differences in change of eGFR and serum creatinine were found between tolvaptan and control groups. Urine flow rate appears to increase significantly with tolvaptan compared to baseline (p<0.0001). The meta-analysis demonstrated no heterogeneity between studies but the possibility of publication bias due to incomplete reporting in excluded studies and lack of RCTs. CONCLUSIONS The safety profile of tolvaptan appears acceptable for patients with HF and CKD. There is evidence for an improvement in serum sodium and reduction in body water without deterioration in renal function. Further research is needed to elucidate the long-term benefits of tolvaptan as an adjunct or alternative to diuretics in such patients.
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3.
Ivabradine.
Komajda, M
Handbook of experimental pharmacology. 2017;:167-175
Abstract
Ivabradine is a blocker of the funny current channels in the sinoatrial node cells. This results in pure heart rate reduction when elevated without direct effect on contractility or on the vessels. It was tested in a large outcome clinical trial in stable chronic heart failure (CHF) with low ejection fraction, in sinus rhythm, on a contemporary background therapy including betablockers (SHIFT Systolic Heart Failure Treatment with the If inhibitor Trial).The primary composite endpoint (cardiovascular mortality or heart failure hospitalization) was reduced by 18% whereas the first occurrence of heart failure hospitalizations was reduced by 26%. The effect was of greater magnitude in patients with baseline heart rate ≥75 beats per minute. Ivabradine improved also the quality of life and induced a reverse remodelling.The safety was overall good with an increase in (a)symptomatic bradycardia and visual side effects.The efficacy and tolerability were similar to those observed in the overall trial in subgroups with diabetes mellitus, low systolic blood pressure (SBP), renal dysfunction or chronic obstructive pulmonary disease (COPD).Ivabradine is indicated in CHF with systolic dysfunction, in patients in sinus rhythm with a heart rate ≥75 bpm in combination with standard therapy including betablocker therapy or when betablocker therapy is contraindicated or not tolerated (European Medicine Agency).
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4.
Network meta-analysis of lorcaserin and oral hypoglycaemics for patients with type 2 diabetes mellitus and obesity.
Neff, LM, Broder, MS, Beenhouwer, D, Chang, E, Papoyan, E, Wang, ZW
Clinical obesity. 2017;(6):337-346
Abstract
In addition to weight loss, randomized controlled trials have shown improvement in glycaemic control in patients taking lorcaserin. The aim of this study aim was to compare adding lorcaserin or other glucose lowering medications to metformin on weight and glycaemic control. A systematic review and network meta-analysis of randomized controlled trials were conducted. Included studies (published 1990-2014) were of lorcaserin or glucose lowering medications in type 2 diabetic patients compared to placebo or different active treatments. Studies had to report ≥1 key outcome (change in weight or HbA1c, % HbA1c <7, hypoglycaemia). Direct meta-analysis was performed using DerSimonian and Laird random effects models, and network meta-analysis with Bayesian Markov-chain Monte Carlo random effects models; 6552 articles were screened and 41 included. Lorcaserin reduced weight significantly more than thiazolidinediones, glinides, sulphonylureas and dipeptidyl peptidase-4 inhibitors, some of which may have led to weight gain. There were no significant differences in weight change between lorcaserin and alpha-glucoside inhibitors, glucagon-like peptide-1 agonists and sodium/glucose cotransporter 2 inhibitors. Network meta-analysis showed lorcaserin was non-inferior to all other agents on HbA1c reduction and % achieving HbA1c of <7%. The risk of hypoglycaemia was not significantly different among studied agents except that sulphonylureas were associated with higher risk of hypoglycaemia than lorcaserin. Although additional studies are needed, this analysis suggests in a population of patients with a body mas index of ≥27 who do not achieve glycaemic control on a single agent, lorcaserin may be added as an alternative to an add-on glucose lowering medication.
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5.
Integrating New Pharmacologic Agents into Heart Failure Care: Role of Heart Failure Practice Guidelines in Meeting This Challenge.
Adams, KF, Giblin, EM, Pearce, N, Patterson, JH
Pharmacotherapy. 2017;(6):645-656
Abstract
Heart failure is well recognized as a major public health concern not only due to severe and frequent adverse health outcomes but also related to the major financial burden this syndrome presents with advancing age in Western societies. Despite the dire need for more efficacious therapies and better application of existing advances, treatment gaps persist, and outcomes in heart failure remain poor, with continually high mortality and morbidity. Treatment guidelines provide one strategy for advancing quality of care in patients with heart failure. This approach, with well-known potential strengths and weaknesses, has both adherents and detractors. Heart failure treatment guidelines have been in sharp focus recently due to updates that address the United States Food and Drug Administration (FDA) approval in 2015 of two new pharmacologic therapies for heart failure with reduced ejection fraction: sacubitril-valsartan and ivabradine. Our commentary will revisit issues in guideline methodology and discuss these in the context of the updates addressing the FDA approval of new pharmacologic agents for heart failure with reduced ejection fraction.
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6.
Tolvaptan Treatment in Children with Chronic Hyponatremia due to Inappropriate Antidiuretic Hormone Secretion: A Report of Three Cases.
Tuli, G, Tessaris, D, Einaudi, S, De Sanctis, L, Matarazzo, P
Journal of clinical research in pediatric endocrinology. 2017;(3):288-292
Abstract
Hyponatremia is the most common electrolyte disorder among hospitalized patients and it is sometimes considered as a poor outcome predictor. Its correction is thus indicated, even in asymptomatic patients. The conventional treatment consists of fluid restriction in presence of euvolemia or hypervolemia; loop diuretics are used in some hypervolemic conditions such as cardiac heart failure, liver cirrhosis and nephrotic syndrome, while intravenous isotonic or hypertonic solutions are administered in hypovolemic conditions. The utilization of demeclocycline and urea is not indicated in pediatric ages due to lack of data on their toxicity and poor tolerance. Recently, a new therapeutic option has been developed, a class of non-peptide arginine vasopressin receptor antagonists called vaptans. Tolvaptan is the only such agent approved in Europe for the treatment of hyponatremia caused by syndrome of inappropriate antidiuretic hormone secretion (SIADH) in adults. In USA, tolvaptan and conivaptan have been approved for treatment of euvolemic and hypervolemic hyponatremia. Few data are so far available in paediatric patients, since only one trial has been registered in Europe which includes children and adolescents, but this trial is still ongoing. Here, we report three children with chronic hyponatremia due to SIADH in which tolvaptan has been used successfully.
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7.
Ivabradine: A Review of Labeled and Off-Label Uses.
Oliphant, CS, Owens, RE, Bolorunduro, OB, Jha, SK
American journal of cardiovascular drugs : drugs, devices, and other interventions. 2016;(5):337-47
Abstract
Ivabradine is a unique medication recently approved in the USA for the treatment of select heart failure patients. It was first approved for use in several countries around the world over a decade ago as an anti-anginal agent, with subsequent approval for use in heart failure patients. Since ivabradine has selective activity blocking the I f currents in the sinus node, it can reduce heart rate without appreciable effects on blood pressure. Given this heart-rate-specific effect, it has been investigated in many off-label indications as an alternative to traditional heart-rate-reducing medications such as beta blockers and calcium channel blockers. We conducted searches of PubMed and Google Scholar for ivabradine, heart failure, HFrEF, HFpEF, angina, coronary artery disease, inappropriate sinus tachycardia, postural orthostatic hypotension, coronary computed tomography angiography and atrial fibrillation. We reviewed and included studies, case reports, and case series published between 1980 and June 2016 if they provided information relevant to the practicing clinician. In many cases, larger clinical trials are needed to solidify the benefit of ivabradine, although studies indicate benefit in most therapeutic areas explored to date. The purpose of this paper is to review the current labeled and off-label uses of ivabradine, with a focus on clinical trial data.
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8.
Conventional management of inappropriate sinus tachycardia.
Olshansky, B, Sullivan, RM
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 2016;(1):43-5
Abstract
Inappropriate sinus tachycardia is a challenging problem to manage. There are limited data on the best method to evaluate and treat the problem. Here, we consider a conventional approach to inappropriate sinus tachycardia.
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9.
Treatment of inappropriate sinus tachycardia with ivabradine.
Annamaria, M, Lupo, PP, Foresti, S, De Ambroggi, G, de Ruvo, E, Sciarra, L, Cappato, R, Calo, L
Journal of interventional cardiac electrophysiology : an international journal of arrhythmias and pacing. 2016;(1):47-53
Abstract
BACKGROUND Inappropriate sinus tachycardia (IST) often causes palpitations, dyspnea, and exercise intolerance, that are generally treated with beta blockers and non-dihydropyridine calcium-channel antagonists. Ivabradine, a selective inhibitor of cardiac pacemaker If current, has recently emerged as an effective and safe alternative to conventional drugs for IST. METHODS We performed a systematic overview of clinical studies on the therapeutic yield of ivabradine in patients with inappropriate sinus tachycardia, published in MEDLINE database from January 2000 to March 2015. RESULTS Overall, five case reports were found, all showing efficacy of ivabradine in subjects affected by IST. Eight non-randomized clinical studies demonstrated short- and medium-term safety and efficacy of ivabradine administration in IST, also in adjunction to or in comparison with metoprolol. One double-blind randomized crossover study also showed that ivabradine is superior to placebo for heart rate (HR) reduction and symptoms control in patients affected by IST. CONCLUSIONS Ivabradine is effective and safe in short- and medium-term treatment of IST. However, long-term follow-up studies and randomized studies comparing ivabradine with beta blockers are still lacking.
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10.
Tolvaptan in Patients Hospitalized With Acute Heart Failure: Rationale and Design of the TACTICS and the SECRET of CHF Trials.
Felker, GM, Mentz, RJ, Adams, KF, Cole, RT, Egnaczyk, GF, Patel, CB, Fiuzat, M, Gregory, D, Wedge, P, O'Connor, CM, et al
Circulation. Heart failure. 2015;(5):997-1005
Abstract
Congestion is a primary reason for hospitalization in patients with acute heart failure (AHF). Despite inpatient diuretics and vasodilators targeting decongestion, persistent congestion is present in many AHF patients at discharge and more severe congestion is associated with increased morbidity and mortality. Moreover, hospitalized AHF patients may have renal insufficiency, hyponatremia, or an inadequate response to traditional diuretic therapy despite dose escalation. Current alternative treatment strategies to relieve congestion, such as ultrafiltration, may also result in renal dysfunction to a greater extent than medical therapy in certain AHF populations. Truly novel approaches to volume management would be advantageous to improve dyspnea and clinical outcomes while minimizing the risks of worsening renal function and electrolyte abnormalities. One effective new strategy may be utilization of aquaretic vasopressin antagonists. A member of this class, the oral vasopressin-2 receptor antagonist tolvaptan, provides benefits related to decongestion and symptom relief in AHF patients. Tolvaptan may allow for less intensification of loop diuretic therapy and a lower incidence of worsening renal function during decongestion. In this article, we summarize evidence for decongestion benefits with tolvaptan in AHF and describe the design of the Targeting Acute Congestion With Tolvaptan in Congestive Heart Failure Study (TACTICS) and Study to Evaluate Challenging Responses to Therapy in Congestive Heart Failure (SECRET of CHF) trials.