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1.
Heart failure drug treatment.
Rossignol, P, Hernandez, AF, Solomon, SD, Zannad, F
Lancet (London, England). 2019;(10175):1034-1044
Abstract
Heart failure is the most common cardiovascular reason for hospital admission for people older than 60 years of age. Few areas in medicine have progressed as remarkably as heart failure treatment over the past three decades. However, progress has been consistent only for chronic heart failure with reduced ejection fraction. In acutely decompensated heart failure and heart failure with preserved ejection fraction, none of the treatments tested to date have been definitively proven to improve survival. Delaying or preventing heart failure has become increasingly important in patients who are prone to heart failure. The prevention of worsening chronic heart failure and hospitalisations for acute decompensation is also of great importance. The objective of this Series paper is to provide a concise and practical summary of the available drug treatments for heart failure. We support the implementation of the international guidelines. We offer views on the basis of our personal experience in research areas that have insufficient evidence. The best possible evidence-based drug treatment (including inhibitors of the renin-angiotensin-aldosterone system and β blockers) is useful only when optimally implemented. However, implementation might be challenging. We believe that disease management programmes can be helpful in providing a multidisciplinary, holistic approach to the delivery of optimal medical care.
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2.
The use of diuretics in heart failure with congestion - a position statement from the Heart Failure Association of the European Society of Cardiology.
Mullens, W, Damman, K, Harjola, VP, Mebazaa, A, Brunner-La Rocca, HP, Martens, P, Testani, JM, Tang, WHW, Orso, F, Rossignol, P, et al
European journal of heart failure. 2019;(2):137-155
Abstract
The vast majority of acute heart failure episodes are characterized by increasing symptoms and signs of congestion with volume overload. The goal of therapy in those patients is the relief of congestion through achieving a state of euvolaemia, mainly through the use of diuretic therapy. The appropriate use of diuretics however remains challenging, especially when worsening renal function, diuretic resistance and electrolyte disturbances occur. This position paper focuses on the use of diuretics in heart failure with congestion. The manuscript addresses frequently encountered challenges, such as (i) evaluation of congestion and clinical euvolaemia, (ii) assessment of diuretic response/resistance in the treatment of acute heart failure, (iii) an approach towards stepped pharmacologic diuretic strategies, based upon diuretic response, and (iv) management of common electrolyte disturbances. Recommendations are made in line with available guidelines, evidence and expert opinion.
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3.
Pivotal clinical trials, meta-analyses and current guidelines in the treatment of hyperkalemia.
Bianchi, S, Regolisti, G
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2019;(Suppl 3):iii51-iii61
Abstract
Hyperkalemia (HK) is the most common electrolyte disturbance observed in patients with advanced stages of chronic kidney disease (CKD), is a potentially life-threatening clinical condition due to an increased risk of fatal arrhythmias, and strongly impacts the quality of life and prognosis of CKD patients. Moreover, while renin-angiotensin-aldosterone system inhibitors (RAASIs) represent the most cardio-nephro-protective drugs used in clinical practice, the treatment with these drugs per se increases serum potassium (sK) values, particularly when heart failure and diabetes mellitus coexist. In fact, the onset or recurrence of HK is frequently associated with not starting, down-titrating or withdrawing RAASIs, and is an indication to begin renal replacement treatment in end-stage renal disease. Current strategies aimed at preventing and treating chronic HK are still unsatisfactory, as evidenced by the relatively high prevalence of HK also in patients under stable nephrology care, and even in the ideal setting of randomized clinical trials. Indeed, dietary potassium restriction, the use of sodium bicarbonate or diuretics, the withdrawal or down-titration of RAASIs, or the administration of old potassium binders, namely sodium polystyrene sulphonate and calcium polystyrene sulphonate, have limited efficacy and are poorly tolerated; therefore, these strategies are not suitable for long-term control of sK. As such, there is an important unmet need for novel therapeutic options for the chronic management of patients at risk for HK. The development of new potassium binders may change the treatment landscape in the near future. This review summarizes the current evidence on the treatment of chronic HK in cardio-renal patients.
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4.
Hyponatremia-Inducing Drugs.
Liamis, G, Megapanou, E, Elisaf, M, Milionis, H
Frontiers of hormone research. 2019;:167-177
Abstract
In clinical practice, several medications such as diuretics, psychotropic drugs, and anticonvulsants have been reported to be a frequent cause of hyponatremia. Drugs may cause hyponatremia either by affecting the homeostasis of sodium and water (e.g., diuretics) or by altering the water homeostasis as a consequence of the syndrome of inappropriate secretion of antidiuretic hormone. On the contrary, drugs commonly prescribed in everyday clinical practice, including proton pump inhibitors, antibiotics, angiotensin-converting enzyme inhibitors, hypoglycemic agents and, amiodarone, have been infrequently 'incriminated' as causes of hyponatremia. Therefore, in the diagnostic approach of patients with low serum [Na+] levels, meticulous history taking and recording of pharmacotherapy is warranted to identify potentially culprit medications. Taking into account the adverse outcomes associated with even mild hyponatremia (i.e., impaired cognition, falls and fractures, mortality), recognition of drug-induced hyponatremia is of vital importance, while responsible agents should be discontinued and "re-challenge" should be avoided by informing the patient and involved caregivers.
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5.
Ascites and Hepatorenal Syndrome.
Adebayo, D, Neong, SF, Wong, F
Clinics in liver disease. 2019;(4):659-682
Abstract
Ascites occurs in up to 70% of patients during the natural history of cirrhosis. Management of uncomplicated ascites includes sodium restriction and diuretic therapy, whereas that for refractory ascites (RA) is regular large-volume paracentesis with transjugular intrahepatic portosystemic shunt being offered in appropriate patients. Renal impairment occurs in up to 50% of patients with RA with type 1 hepatorenal syndrome (HRS) being most severe. Liver transplant remains the definitive treatment of eligible candidates with HRS, whereas combined liver and kidney transplant should be considered in patients requiring dialysis for more than 4 to 6 weeks or those with underlying chronic kidney disease.
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6.
[Hyperkalemia treatment in chronic kidney disease patients: overview on new K binders and possible therapeutic approaches].
De Stefano, T, Borrelli, S, Garofalo, C, Provenzano, M, De Nicola, L, Minutolo, R, Conte, G
Giornale italiano di nefrologia : organo ufficiale della Societa italiana di nefrologia. 2018;(5)
Abstract
Hyperkalaemia is a common complication in patients with nondialysis Chronic Kidney Disease (CKD). It is associated with weakness, paralysis, arrhythmias and increased mortality. Higher serum potassium levels refractory to treatment is one of the most frequent reasons to initiate immediately renal replacement treatment in advanced stages of CKD. Hyperkalaemia is also indirectly associated with the progression of CKD; in fact higher serum potassium levels may lead to withdrawal of renin-angiotensin-system inhibiting drugs that currently represent the most effective tools to postpone ESRD. It is therefore essential to identify patients at higher risk of increase of serum K and to implement therapeutic interventions aimed at preventing and treating hyperkalaemia, such as diet modifications and greater use of diuretics and cation exchange resins. Sodium and calcium-polystyrenesulfonate (SPS) are the resins currently available in Italy. However, few studies showed that SPS is efficacious to reduce serum K and is associated with increased risk of severe adverse effects. Patiromer and ZS-9 represent a significant pharmacological progress in the treatment of hyperkalemia. Indeed, recent studies showed that these novel resins are efficient to reduce serum levels of K with minor occurrence of side effects than polystyrensulfonates. Furthermore, Patiromer, sodium free agent, might have a further advantage in CKD patients, reducing the salt intake in these patients. In addition, ZS-9, being fast-acting drug, might be used also in the treatment of acute hyperkalaemia.
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7.
[Which place for thiazide and thiazide-like diuretics in patients with type 2 diabetes ?].
Scheen, AJ, Krzesinski, JM
Revue medicale de Liege. 2018;(4):176-182
Abstract
The use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. However, these metabolic disturbances are less marked with low-dose of hydrochlorothiazide and with thiazide-like diuretics such as chlorthalidone and indapamide. In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazide(-like) diuretics resulted in a significant reduction in cardiovascular events, all-cause mortality and hospitalization for heart failure compared to placebo. Furthermore, they were shown to be non-inferior to other antihypertensive agents, including blockers of the renin-angiotensin system in diabetic patients without albuminuria. Benefits attributed to thiazide(-like) diuretics (especially at low dose) in terms of cardiovascular protection outweigh the risk of worsening glucose control and inducing other metabolic disorders in patients with type 2 diabetes. Thus low dose thiazide(-like) drugs still play a major role in the treatment of hypertension in patients with type 2 diabetes.
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8.
Type 2 Diabetes and Thiazide Diuretics.
Scheen, AJ
Current diabetes reports. 2018;(2):6
Abstract
PURPOSE OF REVIEW In patients with prediabetes or type 2 diabetes, the use of thiazides as antihypertensive agents has been challenged because associated metabolic adverse events, including new-onset diabetes. RECENT FINDINGS These metabolic disturbances are less marked with low-dose thiazides and, in most but not all studies, with thiazide-like diuretics (chlorthalidone, indapamide) than with thiazide-type diuretics (hydrochlorothiazide). In post hoc analyses of subgroups of patients with hypertension and type 2 diabetes, thiazides resulted in a significant reduction in cardiovascular events, all-cause mortality, and hospitalization for heart failure compared to placebo and generally were shown to be non-inferior to other antihypertensive agents. Benefits attributed to thiazide diuretics in terms of cardiovascular event reduction outweigh the risk of worsening glucose control in type 2 diabetes and of new-onset diabetes in non-diabetic patients. Thiazides still play a key role in the management of patients with type 2 diabetes and hypertension.
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9.
Interventions for preventing high altitude illness: Part 2. Less commonly-used drugs.
Gonzalez Garay, A, Molano Franco, D, Nieto Estrada, VH, Martí-Carvajal, AJ, Arevalo-Rodriguez, I
The Cochrane database of systematic reviews. 2018;(3):CD012983
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Abstract
BACKGROUND High altitude illness (HAI) is a term used to describe a group of mainly cerebral and pulmonary syndromes that can occur during travel to elevations above 2500 metres (˜ 8200 feet). Acute mountain sickness (AMS), high altitude cerebral oedema (HACE) and high altitude pulmonary oedema (HAPE) are reported as potential medical problems associated with high altitude ascent. In this second review, in a series of three about preventive strategies for HAI, we assessed the effectiveness of five of the less commonly used classes of pharmacological interventions. OBJECTIVES To assess the clinical effectiveness and adverse events of five of the less commonly used pharmacological interventions for preventing acute HAI in participants who are at risk of developing high altitude illness in any setting. SEARCH METHODS We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, LILACS and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) in May 2017. We adapted the MEDLINE strategy for searching the other databases. We used a combination of thesaurus-based and free-text search terms. We scanned the reference lists and citations of included trials and any relevant systematic reviews that we identified for further references to additional trials. SELECTION CRITERIA We included randomized controlled trials conducted in any setting where one of five classes of drugs was employed to prevent acute HAI: selective 5-hydroxytryptamine(1) receptor agonists; N-methyl-D-aspartate (NMDA) antagonist; endothelin-1 antagonist; anticonvulsant drugs; and spironolactone. We included trials involving participants who are at risk of developing high altitude illness (AMS or HACE, or HAPE, or both). We included participants with and without a history of high altitude illness. We applied no age or gender restrictions. We included trials where the relevant medication was administered before the beginning of ascent. We excluded trials using these drugs during ascent or after ascent. DATA COLLECTION AND ANALYSIS We used the standard methodological procedures employed by Cochrane. MAIN RESULTS We included eight studies (334 participants, 9 references) in this review. Twelve studies are ongoing and will be considered in future versions of this review as appropriate. We have been unable to obtain full-text versions of a further 12 studies and have designated them as 'awaiting classification'. Four studies were at a low risk of bias for randomization; two at a low risk of bias for allocation concealment. Four studies were at a low risk of bias for blinding of participants and personnel. We considered three studies at a low risk of bias for blinding of outcome assessors. We considered most studies at a high risk of selective reporting bias.We report results for the following four main comparisons.Sumatriptan versus placebo (1 parallel study; 102 participants)Data on sumatriptan showed a reduction of the risk of AMS when compared with a placebo (risk ratio (RR) = 0.43, CI 95% 0.21 to 0.84; 1 study, 102 participants; low quality of evidence). The one included study did not report events of HAPE, HACE or adverse events related to administrations of sumatriptan.Magnesium citrate versus placebo (1 parallel study; 70 participants)The estimated RR for AMS, comparing magnesium citrate tablets versus placebo, was 1.09 (95% CI 0.55 to 2.13; 1 study; 70 participants; low quality of evidence). In addition, the estimated RR for loose stools was 3.25 (95% CI 1.17 to 8.99; 1 study; 70 participants; low quality of evidence). The one included study did not report events of HAPE or HACE.Spironolactone versus placebo (2 parallel studies; 205 participants)Pooled estimation of RR for AMS was not performed due to considerable heterogeneity between the included studies (I² = 72%). RR from individual studies was 0.40 (95% CI 0.12 to 1.31) and 1.44 (95% CI 0.79 to 2.01; very low quality of evidence). No events of HAPE or HACE were reported. Adverse events were not evaluated.Acetazolamide versus spironolactone (1 parallel study; 232 participants)Data on acetazolamide compared with spironolactone showed a reduction of the risk of AMS with the administration of acetazolamide (RR = 0.36, 95% CI 0.18 to 0.70; 232 participants; low quality of evidence). No events of HAPE or HACE were reported. Adverse events were not evaluated. AUTHORS' CONCLUSIONS This Cochrane Review is the second in a series of three providing relevant information to clinicians and other interested parties on how to prevent high altitude illness. The assessment of five of the less commonly used classes of drugs suggests that there is a scarcity of evidence related to these interventions. Clinical benefits and harms related to potential interventions such as sumatriptan are still unclear. Overall, the evidence is limited due to the low number of studies identified (for most of the comparison only one study was identified); limitations in the quality of the evidence (moderate to low); and the number of studies pending classification (24 studies awaiting classification or ongoing). We lack the large and methodologically sound studies required to establish or refute the efficacy and safety of most of the pharmacological agents evaluated in this review.
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10.
Resistant Hypertension: Which Agent?
Prosser, HCG, Azzam, O, Schlaich, MP
Heart, lung & circulation. 2018;(8):911-916
Abstract
Resistant hypertension is commonly defined as office blood pressure above recommended target despite the use of optimal doses of at least three antihypertensive drugs including a diuretic. Australian guidelines recommend combination of blockers of the renin-angiotensin system, either ACE inhibitors or angiotensin receptor blockers, with calcium channel blockers and diuretics as the preferred triple therapy. A substantial proportion of hypertensive patients will require additional pharmacotherapy to achieve or get close to target blood pressure levels. Here we briefly review the evidence currently available to provide guidance on the most appropriate choice for additional antihypertensive pharmacotherapy and touch on interventional approaches that may be considered in some patients.