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Nitrates for the Management of Acute Heart Failure Syndromes

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Nitrates for the Management of Acute Heart Failure Syndromes edicine: O M p y e c n n A e c g c r e e s s m E Emergency Medicine: Open Access Shoaib et al., Emerg Med (Los Angel) 2016, 6:3 ISSN: 2165-7548 DOI: 10.4172/2165-7548.1000320 Review Article Open Access Nitrates for the Management of Acute Heart Failure Syndromes Ahmad Shoaib1*, Mohamed Farag2 and Diana A Gorog3 1Academic Cardiology, University of Hull, UK 2Postgraduate Medical School, University of Hertfordshire, UK 3National Heart & Lung Institute, Imperial College, London, UK *Corresponding author: Ahmad Shoaib, Academic Cardiology, University of Hull, UK, Tel: 00447414838011; E-mail: [email protected] Received date: September 07, 2015; Accepted date: April 21, 2016; Published date: April 28, 2016 Copyright: © 2016 Shoaib A, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Abstract Intravenous nitrates are widely used in the management of acute heart failure syndrome (AHFS), yet with lack of robust evidence to support their use. We therefore sought to analyse all randomised studies that evaluated the effects of nitrates on clinical outcomes in patients with AHFS. In total, fifteen relevant trials comparing nitrates and alternative interventions in 1824 patients were identified. All but three were conducted before 1998. No trials demonstrated a beneficial effect on mortality, apart from one trial reporting a reduction in mortality, which was related to the time of treatment. Retrospective review suggests that there is a lack of data to draw any firm conclusions concerning the use of nitrates in patients with AHFS, which is surprising given the widespread use of nitrates. More studies are needed to evaluate the safety and efficacy of these agents in the modern era of guideline-directed use of heart failure therapy. Keywords: Acute heart failure syndrome; Nitrates; Vasodilator Historical drug treatments for heart failure syndromes included therapy; Morbidity; Mortality only diuretics and digitalis, mainly for the relief of symptoms of congestion rather than for a mortality benefit [4]. This had prompted Abbreviations further search into evaluating other agents as potential treatments, especially in patients with advanced heart failure. In the early 1970s, ACEI: Angiotensin Onverting Enzyme Inhibitors; ADHF: Acute initial vasodilator studies in heart failure showed some added Decompensated Heart Failure; AHFS: Acute Heart Failure Syndrome; haemodynamic benefits with the use of nitrates, mainly by reducing ARB: Angiotensin Receptor Blockers; BB: Beta Adrenoceptor preload [5,6]. Interest in nitrate therapy has increased further as a Antagonists; IHD: Ischaemic Heart Disease;ISDN: Isosorbide result of the widespread use of intravenous nitrates in the emergency Dinitrate; ISMN: Isosorbide Mononitrate; MRA: Mineralocorticoid management of AHFS. Observational studies suggested that the Receptor Antagonists; N: Nitrates; NYHA: New York Heart addition of the nitric oxide donor isosorbide dinitrate (ISDN) in acute Association decompensated heart failure (ADHF) was associated with lower all- cause mortality and favourable long-term clinical outcomes, but Introduction without reduction in rehospitalisation rate [7,8]. Heart failure is a chronic, progressive clinical syndrome that results Standard guideline-directed therapy for heart failure has changed from any structural or functional impairment of ventricular filling or dramatically over the last 25 years [9]. The beneficial effects of nitrates ejection of blood causing symptoms and signs of pulmonary may or may not have been masked by newer heart failure treatments. congestion [1]. Acute heart failure syndrome (AHFS) is defined as the Moreover, it is unclear whether nitrates can significantly improve sudden change or the rapid deterioration of symptoms and signs of symptoms of heart failure, although it is widely believed that they do. It heart failure, often in response to certain precipitating factors (for is also uncertain whether the effect of these agents confers a different example, myocardial ischaemia, cardiac arrhythmia, septicaemia and effect on different heart failure phenotypes (for example, heart failure non-compliance with either drug, or diet therapy, or both), which with preserved systolic function, heart failure with reduced systolic require urgent medical attention [2]. Over the last 25 years, despite function, ischaemic heart disease, valve disease, etc). Previous reviews advances in heart failure diagnosis and management, it remains a that studied nitrates in acute heart failure have been small, and common yet complex syndrome associated with high rates of included only few studies [10,11]. Perhaps, this is due, in part, to the morbidity and mortality. Indeed, heart failure continues to represent a fact that most prior studies are considered old with inaccurate major and growing burden on public health worldwide, both in terms methods, which might have shaped final results. Recently, a study of of its magnitude and poor prognosis. This is, at least in part, because home monitoring using a pulmonary artery pressure monitoring the contemporary medications that are received by heart failure device demonstrated a substantial reduction in rehospitalisation rate patients have been proven insufficient to fully prevent hospitalisations with similar trends for death in patients with symptomatic heart failure [3]. Also, there has been a little research in the management of AHFS, [12]. Apart from diuretics, nitrates were the main agents used to with many treatment strategies based on clinical experience rather reduce pulmonary pressures, which appeared to be the main than on evidence from high quality studies. mechanism by which the benefit was achieved. We therefore sought to analyse all randomised studies that evaluated the effects of nitrates on clinical outcomes in patients with AHFS. Emerg Med (Los Angel) Volume 6 • Issue 3 • 1000320 ISSN:2165-7548 EGM, an open access journal Citation: Shoaib A, Farag M, Gorog DA (2016) Nitrates for the Management of Acute Heart Failure Syndromes. Emerg Med (Los Angel) 6: 320. doi:10.4172/2165-7548.1000320 Page 2 of 7 Mechanism of Action of Nitrates including 35 patients with a mean age of 51±8 years studied a combination therapy of nitrates and hydralazine. Of which, one study Many nitrates (e.g. nitroglycerine, isosorbide mononitrate and compared the combination to either drug used alone and the other one isosorbide dinitrate) exert their effects in the human body by being compared the combination to captopril and prazosin. For nitrates converted to nitric oxide (NO). NO is recognized as the most alone, 14 studies were identified, of which 13 studies included 1714 important cellular signalling molecule involved in many physiological patients with a mean age of 62 ± 8 years and 17% were women, and pathological cardiovascular processes [13]. There has been a compared nitrates to alternative interventions, and one study growing body of evidence to suggest that NO production, as a potent compared a high dose nitrate to a low dose nitrate (Table 1). The natural vasodilator and a major biological regulator of cardiovascular majority of studies assessed the effects in men with acute function, is impaired in patients with heart failure, thus indicating a decompensated heart failure (ADHF) due predominantly to left potential significant beneficial effect of NO enhancing therapy with ventricular systolic dysfunction (LVSD). The aetiology of heart failure nitrates [14,15]. was ischaemic heart disease (IHD) in about 76% of patients among all Fifteen randomised studies including 1824 AHFS patients and studies. reporting clinical outcomes were identified. Two small studies Study D Treatmen Control Patient Age Women Follow Backgroun SR LVSD IHD NY Sympto PAWP Cardiac Mortalit e t s (n) (mean (%) - Up d therapy (%) (%) (%) HA ms index y s ) III/I i V g (%) n Cohn, P Sodium Placebo 812 59 0% 13 D, L NR 100% 100 100 NR NR NR Related [15] a Nitropruss weeks % % to time r ide (94.4 of a mcg / min) treatme ll IV nt * e l Nelson P ISDN 30.5 Hydralazine 20 56 0% 3 L [used 100 100% 100 100 Favoured No Favoure None , [16] a mg IV 11.7 mg IV hours after % % % ISDN difference d r randomizati Hydrala a on] zine ll e l Nelson P ISDN 13.2 Furosemide 28 56 0% 90 None 100 100% 100 100 Favoured No Favoure None , [17] a mg IV 80 mg IV minute % % % ISDN difference d ISDN r s a ll e l Nelson P ISDN Hydralazine 20 58 0% 90 L [used 100 100% 100 100 Favoured No Favoure None , [18] a (50-200 (0.15mg/kg) minute before % % % ISDN difference d r mcg/kg/h) IV s randomizati Hydrala a IV on] zine ll e l Dubour P ISDN 40 Placebo 20 60 15% 8 None 100 100% 100 100 NR Favoured No None g, [19] a mg PO hours % % % ISDN differenc r e a ll e l Nelson P ISDN 14.3 Hydralazine 20 51 0% 4.30 Furosemide 100 100% 100 100 No No No No , [20] a mg IV 12.3 mg IV hours 82 mg IV & % % % difference difference differenc differenc r B1 agonist, e e a +ve ll inotropic e (Prenalterol) l 12 mg IV, [used at Emerg Med (Los Angel) Volume 6 • Issue 3 • 1000320 ISSN:2165-7548 EGM, an open access journal Citation: Shoaib A, Farag M, Gorog DA (2016) Nitrates for the Management of Acute Heart Failure Syndromes. Emerg Med (Los Angel) 6: 320. doi:10.4172/2165-7548.1000320 Page 3 of 7 randomizati on] Nelson P ISDN 24.1 Hydralazine 12 59 0% 90 None 100 100% 100 100 Favoured Favoured Favoure None , [21] a mg IV 11.9
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