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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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Clinical effect of trimetazidine on prevention of contrast-induced nephropathy in patients with renal insufficiency: An updated systematic review and meta-analysis.
Ye, Z, Lu, H, Su, Q, Guo, W, Dai, W, Li, H, Yang, H, Li, L
Medicine. 2017;(9):e6059
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Abstract
BACKGROUND With the continuous development of cardiac interventional medicine, the incidence of contrast-induced nephropathy (CIN) is increasing every year, which is a serious threat to people's physical and mental health. Trimetazidine (TMZ) is a type of anti-ischemic drug developed in recent years, which can significantly reduce the incidence of CIN. At present, a systematic review and meta-analysis was conducted to evaluate the clinical effect of TMZ on prevention of CIN in patients with renal insufficiency. However, the study did not include patients from other countries and speaking different languages. So we conducted this study to update the previous meta-analysis that investigated the effects of TMZ on prevention of CIN in patients with renal insufficiency, and provided some theoretical reference for clinical. METHODS By searching PubMed, Embase, the Cochrane Library, Web of Science, CBM, CNKI, VIP database, and Wang Fang database for randomized controlled trial, which is comparing TMZ versus conventional hydration for prevention of CIN. Two researchers independently screened literature, and then evaluated the quality of literature and extracted the relevant data. Stata 11.0 software was used for statistical analysis. RESULTS Finally, this updated review showed that 3 studies that were not included in the previous meta-analysis were included in our study (3 articles were published in the Chinese Journal, 1 study for CIN, 1 study for CIN, serum creatinine (Scr), and superoxide dismutase, 1 study for CIN and Scr), and 1 outcome (Scr) reflecting the change of renal function was additionally included in our study. Of the 932 studies, 6 randomized controlled trials met the criteria, including 377 patients in TMZ group and 387 patients in control group. This meta-analysis for all studies showed that TMZ can significantly reduce the incidence of CIN (relative risk 0.27, 95% confidence interval [CI] 0.16, 0.46, P = 0.000), and can decrease the level of Scr after operation, including Scr of postoperative 24 hours (standardized mean difference [SMD] -0.30, 95% CI -0.51, -0.09, P = 0.005), Scr of postoperative 48 hours (SMD -0.66, 95% CI -1.23, -0.10, P = 0.022), and Scr of postoperative 7 days (SMD -0.74, 95% CI -1.36, -0.11, P = 0.021). However, the Scr of postoperative 72 hours between TMZ group and control group has no statistical significance (P = 0.362). CONCLUSION Our study showed that when comparing with conventional hydration, TMZ can significantly reduce the incidence of CIN and the level of postoperative Scr. Therefore, we could suggest that TMZ was superior to conventional hydration for the treatment of CIN in patients with renal insufficiency. However, due to the restriction of quality and number of included articles, it still needs to carry out multicenter, randomized, double-blind clinical trials to confirm this conclusion in the future.
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Agents with vasodilator properties in acute heart failure.
Singh, A, Laribi, S, Teerlink, JR, Mebazaa, A
European heart journal. 2017;(5):317-325
Abstract
Millions of patients worldwide are admitted for acute heart failure (AHF) each year and physicians caring for these patients are confronted with the short-term challenges of reducing symptoms while preventing end organ dysfunction without causing additional harm, and the intermediate-term challenges of improving clinical outcomes such as hospital readmission and survival. There are limited data demonstrating the efficacy of any currently available therapies for AHF to meet these goals. After diuretics, vasodilators are the most common intravenous therapy for AHF, but neither nitrates, nitroprusside, nor nesiritide have robust evidence supporting their ability to provide meaningful effects on clinical outcomes, except perhaps early symptom improvement. Recently, a number of novel agents with vasodilating properties have been developed for the treatment of AHF. These agents include serelaxin, natriuretic peptides (ularitide, cenderitide), β-arrestin-biased angiotensin II type 1 receptor ligands (TRV120027), nitroxyl donors (CXL-1020, CXL-1427), soluble guanylate cyclase modulators (cinaciguat, vericiguat), short-acting calcium channel blockers (clevidipine), and potassium channel activators (nicorandil). These development programmes range from the stage of early dose-finding studies (e.g. TRV120027, CXL-1427) to large, multicentre mortality trials (e.g. serelaxin, ularitide). There is an urgent need for agents with vasodilating properties that will improve both in-hospital and post-discharge clinical outcomes, and these novel approaches may provide opportunities to address this need.
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Effect of cilostazol in treating diabetes-associated microvascular complications.
Asal, NJ, Wojciak, KA
Endocrine. 2017;(2):240-244
Abstract
PURPOSE Cilostazol (Pletal), a phosphodiesterase-3 inhibitor, was approved in the United States in 1999 to reduce symptoms of intermittent claudication. Cyclic adenosine monophosphate levels increase from inhibition of phosphodiesterase resulting in anti-platelet, anti-inflammatory, and vasodilatory effects. Diabetes mellitus is a chronic disease that causes endothelial and platelet dysfunction leading to both microvascular and macrovascular complications. This mini-review highlights the emerging evidence suggesting benefits of using cilostazol in treating microvascular complications associated with diabetes mellitus. METHODS A review of literature was conducted using PubMed and Embase databases focusing on cilostazol use in diabetes mellitus. RESULTS Cilostazol demonstrated renoprotective effects in patients with diabetic nephropathy by reducing serum soluble adhesion molecule-1 and monocyte chemoattractant protein-1. Cilostazol's anti-inflammatory actions predictably attenuate glomerular damage from increased leukocyte adherence. Additionally, cilostazol delayed renal dysfunction secondary to type 2 diabetes mellitus as albuminuria was reduced most likely resulting from inhibition of nuclear factor kappa-induced inflammatory and endothelial markers. Cilostazol's anti-inflammatory actions in addition to its vasodilatory actions relieved retinal hypoxia and decreased excessive production of retinal blood vessels suggesting benefit in diabetic retinopathy. Cilostazol did not improve neuropathy symptom scores signifying that it may not be as beneficial in patients with diabetic peripheral neuropathy without diabetic nephropathy or diabetic retinopathy. CONCLUSIONS Cilostazol's pleiotropic effects may be beneficial in patients with type 2 diabetes mellitus and diabetic nephropathy. Additional, larger studies need to be conducted to assess the benefits and risks of using cilostazol as an alternative agent in treating patients with diabetic microvascular complications.