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Recent advances in pharmacological treatment of heart failure.
Iacoviello, M, Palazzuoli, A, Gronda, E
European journal of clinical investigation. 2021;(11):e13624
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Abstract
BACKGROUND Over the last years, several trials offered new evidence on heart failure (HF) treatment. DESIGN AND RESULTS For HF with reduced left ventricular ejection fraction, type 2 sodium-glucose cotransporter inhibitors, aside from sacubitril-valsartan, demonstrated extraordinary efficacy in ameliorating patients' prognosis. Some new molecules (eg vericiguat, omecamtiv mecarbil and ferric carboxymaltose) correct iron deficiency and have shown to be capable of furthering reducing the burden of HF hospitalisation. Finally, there is new evidence on the possible therapeutic approaches of HF patients with mid-range or preserved left ventricular ejection fraction. CONCLUSIONS This review aimed to revise the main novelties in the field of HF therapy and focus on how the daily clinical approach to patient treatment is changing.
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Hypothesis: The potential therapeutic role of nicorandil in COVID-19.
Ashour, H, Elsayed, MH, Elmorsy, S, Harb, IA
Clinical and experimental pharmacology & physiology. 2020;(11):1791-1797
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At present, there is yet no specific antiviral treatment or immunization against the newly identified human severe acute respiratory syndrome virus (SARS-CoV2) that results in a rapidly progressive pandemic coronavirus disease 2019 (COVID-19). We believe in a crucial need for a clinical strategy to counteract this viral pandemic based on the known pathogenesis throughout the disease course. Evidence suggests that exaggerated patient's inflammatory response and oxidative stress are likely to aggravate the disease pathology. The resulting endothelial dysfunction further induces fibrosis and coagulopathy. These disturbances can generate severe acute respiratory distress syndrome (ARDS) that can progress into respiratory and circulatory failure. Nicorandil is an anti-anginal vasodilator drug acts by increasing nitric oxide bioavailability and opening of the KATP channel. Recently, nicorandil has been recognized to possess multiple protective effects against tissue injury. Here, we address a possible modulatory role of nicorandil against COVID-19 pathogenesis. We hypothesise nicorandil would be an effective form of adjuvant therapy against COVID-19.
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Effects of mitochondrial ATP-sensitive potassium channel activation (nicorandil) in patients with angina pectoris undergoing elective percutaneous coronary interventions: A meta-analysis of randomized controlled trials.
Zhu, H, Xu, X, Fang, X, Zheng, J, Chen, T, Huang, J
Medicine. 2019;(3):e14165
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Abstract
AIMS: Nicorandil, which is a mitochondrial ATP-sensitive potassium channel opener, is believed to improve perioperative myocardial injury (PMI) in patients undergoing percutaneous coronary intervention (PCI), but recent studies have shown that nicorandil treatment did not improve functional and clinical outcomes in patients with angina pectoris who underwent elective PCI. We performed a meta-analysis to investigate the protective effect of nicorandil on perioperative injury in patients with angina pectoris who underwent elective PCI. METHODS The Medline, EMBASE, and Cochrane databases were searched for randomized clinical trials examining the effects of nicorandil. Two investigators independently selected suitable trials, extracted data, and assessed trial quality. RESULTS Seven studies of patients undergoing elective PCI, comprising a total of 979 patients, were included in this review. The results showed that nicorandil did not reduce the levels of markers of myocardial injury (standardized mean difference [SMD] 0.31 [95%CI -0.6, 1.22] for creatine kinase-MB [CK-MB] and 1.29 [95%CI -2.18, 4.76] for troponin I [TNI]), perioperative complications (relative risk [RR] 0.91 [95%CI 0.46-1.81]), target vessel revascularization (RR 0.79 [95%CI 0.50-1.25]) or major adverse cardiac events (MACE) (RR 0.83 [95%CI 0.49-1.43]). Nicorandil did reduce the corrected TIMI frame count (SMD-0.30 [95%CI -0.52, -0.09]). CONCLUSION Although nicorandil did not reduce the overall incidence of perioperative complications and the incidence of major adverse cardiac events (MACE) in patients with angina pectoris who underwent elective PCI, it could still improve no reflow and slow coronary flow.
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An update on current and emerging treatments for pulmonary arterial hypertension in childhood and adolescence.
Wacker, J, Weintraub, R, Beghetti, M
Expert review of respiratory medicine. 2019;(2):205-215
Abstract
Pulmonary hypertension is a severe condition that can develop during childhood due to several different etiologies. During the last two decades, based on a better understanding of the underlying pathobiology leading to pulmonary arterial hypertension, targeted therapies have been developed and have improved the dreadful prognosis of the condition. However, curative therapy remains elusive. Areas covered: In this article, we will review the currently available drugs in pediatric pulmonary arterial hypertension and discuss the recommended management strategies. Expert commentary: Most of the drugtrials in pulmonary hypertension have been performed in adults, with extrapolation of the results to children. Most of the pediatric studies are non-controlled. The rarity of the disease and the lack of identifiable pediatric treatment goals and satisfactory trial end-points could explain the paucity of specific pediatric studies. An evolution has been made in the last few years regarding the treatment strategy of pulmonary arterial hypertension, with evidence that early combination therapy with at least two pulmonary vasodilators was beneficial on the survival. Children with pulmonary hypertension should be referred to experienced centers early, to benefit from a comprehensive initial assessment. Serial clinical and hemodynamic re-evaluation should assess treatment response and guide potential change in therapy.
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Pharmacologic Management of Portal Hypertension.
Bunchorntavakul, C, Reddy, KR
Clinics in liver disease. 2019;(4):713-736
Abstract
Terlipressin, somatostatin, or octreotide are recommended as pharmacologic treatment of acute variceal hemorrhage. Nonselective β-blockers decrease the risk of variceal hemorrhage and hepatic decompensation, particularly in those 30% to 40% of patients with good hemodynamic response. Carvedilol, statins, and anticoagulants are promising agents in the management of portal hypertension. Recent advances in the pharmacologic treatment of portal hypertension have mainly focused on modifying an increased intrahepatic resistance through nitric oxide and/or modulation of vasoactive substances. Several novel pharmacologic agents for portal hypertension are being evaluated in humans.
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Acute Decompensated Heart Failure.
Hammond, DA, Smith, MN, Lee, KC, Honein, D, Quidley, AM
Journal of intensive care medicine. 2018;(8):456-466
Abstract
Heart failure (HF) is a societal burden due to its high prevalence, frequent admissions for acute decompensated heart failure (ADHF), and the economic impact of direct and indirect costs associated with HF and ADHF. Common etiologies of ADHF include medication and diet noncompliance, arrhythmias, deterioration in renal function, poorly controlled hypertension, myocardial infarction, and infections. Appropriate medical management of ADHF in patients is guided by the identification of signs and symptoms of fluid overload or low cardiac output and utilization of evidence-based practices. In patients with fluid overload, various strategies for diuresis or ultrafiltration may be considered. Depending on hemodynamics and patient characteristics, vasodilator, inotropic, or vasopressor therapies may be of benefit. Upon ADHF resolution, patients should be medically optimized, have lifestyle modifications discussed and implemented, and medication concierge service considered. After discharge, a multidisciplinary HF team should follow up with the patient to ensure a safe transition of care. This review article evaluates the management options and considerations when treating a patient with ADHF.
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Comparison of sodium nitroprusside and adenosine for fractional flow reserve assessment: a systematic review and meta-analysis.
Solernó, R, Pedroni, P, Mariani, J, Sarmiento, R
Expert review of cardiovascular therapy. 2018;(10):765-770
Abstract
BACKGROUND Fractional flow reserve (FFR) has become a useful tool in the assessment of physiological significance of coronary artery stenosis (CAS), and Adenosine (ADE) is associated with a high incidence of transient side effects. Sodium nitroprusside (NPS) has been proposed as an alternative vasodilator agent. A meta-analysis of studies comparing ADE and NPS for FFR assessment in the same coronary lesions was performed. METHODS Authors searched for articles comparing NPS and ADE for FFR assessment in intermediate coronary lesions published through January 2018. The following keywords were used: 'fractional flow reserve' AND 'nitroprusside'. Data were summarized using weighted mean differences for paired data. RESULTS Seven studies were identified comprising 342 patients and 401 lesions. Four studies evaluated intravenous ADE and 3 studies intracoronary ADE administration. Weighted means FFR values obtained with ADE and NPS were 0.8411 and 0.8445, respectively (weighted mean difference: 0.00, 95% confidence interval (CI) -0.01 to 0.01, p = 0,548). Adverse events were significantly reduced with IC NPS (RR = 0.08, 95%CI 0.02-0.30, P < 0.0001). CONCLUSIONS NPS produces similar FFR measurements compared to ADE with a significant reduction in adverse effects. These results may support its use as a suitable alternative to ADE for FFR assessment.
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Pulmonary Vasodilators and Anesthesia Considerations.
Green, JB, Hart, B, Cornett, EM, Kaye, AD, Salehi, A, Fox, CJ
Anesthesiology clinics. 2017;(2):221-232
Abstract
Pulmonary hypertension (PH) is a complex disease process of the pulmonary vasculature system characterized by elevated pulmonary arterial pressures. Patients with PH are at increased risk for morbidity and mortality, including intraoperatively and postoperatively. Appreciation by the clinical anesthesiologist of the pathophysiology of PH is warranted. Careful and meticulous strategy using appropriate anesthetic medications, pulmonary vasodilator and inotropic agents, and careful fluid management all increase the likelihood of the best possible outcome in this challenging patient population.
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Pediatric pulmonary arterial hypertension: on the eve of growing up.
Douwes, JM, Berger, RMF
Current opinion in pulmonary medicine. 2017;(5):398-403
Abstract
PURPOSE OF REVIEW Current recommendations for diagnosis and treatment of pulmonary arterial hypertension (PAH) during childhood are expert opinion based, because of lacking pediatric data. In recent years, however, important pediatric data have emerged on PAH. RECENT FINDINGS PAH in children shows similarities as well as differences compared to adults. Neonates and children know specific clinical presentations and a hemodynamic profile that differs from adults with PAH. Children identified as acute vasodilator responders according to the criteria proposed for adults rather than the pediatric criteria have better outcome when treated with calcium channel blockers. For nonresponders, combination PAH-targeted therapy leads to improved outcome compared to monotherapy. In pediatric PAH, WHO functional class, N-terminal pro-brain natriuretic peptide and tricuspid annular plane systolic excursion were identified as surrogates for survival and therefore qualify to be treatment goals in a goal-oriented treatment strategy. SUMMARY In order to refine current pediatric treatment guidelines, data on efficacy of specific treatment regiments and strategies are needed. The recently validated composite endpoint of clinical worsening allows for trials that will provide these data. For the first time, evidence-based treatment goals have been identified that will allow for a goal-oriented treatment strategy. Furthermore, various prognostic predictors have been identified that may prove treatment goals in future.
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Heart Failure Guidelines on Pharmacotherapy.
Papadimitriou, L, Hamo, CE, Butler, J
Handbook of experimental pharmacology. 2017;:109-129
Abstract
Heart Failure (HF) is a serious emerging Public Health issue mainly in the high-income countries. In the USA, more than 6 million adults are affected. Despite the latest advances in device and pharmacological therapeutics, it still carries a huge burden, partially reflected in the annual healthcare cost of approximately $30 billion (2012) and the 5 year mortality rate of 50%. In this article, we review the medications, proven to significantly reduce mortality and morbidity in HF patients with structural myocardial disease and past or current symptoms, based on the latest North American HF guidelines. We, finally, perform a brief comparison between the former recommendations and the published 2016 HF guidelines by European Society of Cardiology.