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Angiotensin Type 1 Receptor Blockers in Heart Failure.
Singh, KD, Karnik, SS
Current drug targets. 2020;(2):125-131
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Abstract
Homeostasis in the cardiovascular system is maintained by physiological functions of the Renin Angiotensin Aldosterone System (RAAS). In pathophysiological conditions, over activation of RAAS leads to an increase in the concentration of Angiotensin II (AngII) and over activation of Angiotensin Type 1 Receptor (AT1R), resulting in vasoconstriction, sodium retention and change in myocyte growth. It causes cardiac remodeling in the heart which results in left ventricular hypertrophy, dilation and dysfunction, eventually leading to Heart Failure (HF). Inhibition of RAAS using angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) has shown to significantly reduce morbidity and mortality due to HF. ACEi have been shown to have higher drug withdrawal rates due to discomfort when compared to ARBs; therefore, ARBs are the preferred choice of physicians for the treatment of HF in combination with other anti-hypertensive agents. Currently, eight ARBs have been approved by FDA and are clinically used. Even though they bind to the same site of AT1R displacing AngII binding but clinical outcomes are significantly different. In this review, we described the clinical significance of each ARB in the treatment of HF and their clinical outcome.
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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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Sacubitril and valsartan fixed combination to reduce heart failure events in post-acute myocardial infarction patients.
Zaid Iskandar, M, Lang, CC
Drugs of today (Barcelona, Spain : 1998). 2017;(10):545-551
Abstract
Heart failure is a term used to define a constellation of symptoms and signs that are commonly attributed to the inability of the heart to produce a cardiac output that meets the demands of the body. It remains a deadly disease, affecting between 1-2% of the population, and is more common in the elderly, with around 6-10% of patients over 65 suffering from the condition. Sacubitril/valsartan (LCZ-696) is a combined neprilysin inhibitor and angiotensin AT1 receptor blocker approved in recent years for the treatment of chronic heart failure with reduced ejection fraction. In an area where there have been limited pharmacological advances in the last 10 years, this drug was a game changer and a much welcomed addition to contemporary heart failure therapy. It is currently being studied in patients with heart failure with preserved ejection fraction and for the reduction of heart failure events post-acute myocardial infarction. Results from the ongoing PARADISE-MI study are awaited by the global cardiology community with great interest.
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The impact of angiotensin receptor blockers on arterial stiffness: a meta-analysis.
Peng, F, Pan, H, Wang, B, Lin, J, Niu, W
Hypertension research : official journal of the Japanese Society of Hypertension. 2015;(9):613-20
Abstract
Some studies reported a protective role of angiotensin receptor blockers (ARBs) against arterial stiffness. Therefore, we performed a meta-analysis of published clinical trials to systematically assess the impact of ARBs on arterial stiffness as measured by using pulse wave velocity (PWV). Eligible articles were identified by searching PubMed, EMBASE, Cochrane, Wanfang and CNKI databanks before 31 July 2014. The data were extracted independently and in duplicate. Forty articles including 53 clinical trials qualified, including 1650 and 1659 subjects in ARB treatment and control groups, respectively. Overall reductions in carotid-femoral PWV (cfPWV) and brachial-ankle PWV (baPWV) were statistically significant, with an average of -42.52 cm s(-1) (95% CI: -81.82 to -3.21; P=0.034) and -107.08 cm s(-1) (95% CI: -133.98 to -80.18; P<0.0005), respectively, after receiving ARBs. Subgroup analysis by ARB type revealed that telmisartan (weighted mean difference or WMD=-100.82 cm s(-1); P<0.0005) and valsartan (WMD=-104.59 cm s(-1); P<0.0005) significantly reduced baPWV, but only valsartan reduced cfPWV (WMD=-65.58; P=0.030). cfPWV was significantly reduced in comparisons of ARBs with placebo (WMD=-79.65 cm s(-1); P=0.001), and baPWV was significantly reduced with calcium channel blockers (WMD=-130.74 cm s(-1); P<0.0005). There were low probabilities of publication bias. Taken together, our findings support the important role of ARB treatment in improving arterial stiffness.
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5.
Advances in the pathophysiology and treatment of heart failure with preserved ejection fraction.
Tannenbaum, S, Sayer, GT
Current opinion in cardiology. 2015;(3):250-8
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Abstract
PURPOSE OF REVIEW With the failure of multiple trials to identify a successful therapy for heart failure with preserved ejection fraction (HFpEF), attention has shifted to defining specific phenotypes within the HFpEF spectrum in an effort to develop a targeted approach to treatment. Here we summarize the most recent studies investigating the pathophysiology and clinical features of HFpEF, and discuss recent clinical trials in the context of developing treatments that look toward the underlying cause of this disorder. RECENT FINDINGS Advances in basic science and clinical research have further characterized HFpEF, identifying multiple pathophysiological mechanisms that ultimately lead to exercise intolerance and volume overload. The success of small studies focused on specific subsets of the HFpEF population has promoted the concept that there may not be one treatment strategy that can universally be applied to HFpEF. SUMMARY HFpEF is associated with significant morbidity and mortality and accounts for approximately half of patients with chronic heart failure. HFpEF is a complex disease, encompassing a diverse cohort of patients and marked by the presence of multiple etiological mechanisms. The failure to develop successful therapies for the management of HFpEF may be because of inadequate standardization of the HFpEF diagnosis, overly broad inclusion criteria and inadequate differentiation of disease subtypes. Given the heterogeneity among patients with HFpEF, much of the current research is focused on understanding of pathophysiology and identifying disease phenotypes that may respond to a targeted treatment approach. Several newer approaches, including neprilysin inhibition and device therapy, offer promise for a new era of HFpEF treatment.
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Treatment of FSGS in Children.
Sethna, CB, Gipson, DS
Advances in chronic kidney disease. 2014;(2):194-9
Abstract
Focal segmental glomerulosclerosis (FSGS) is a pathologic condition that represents many disease entities. The goals of therapy are to cure the disease. When this is not possible, the secondary goals are to reduce proteinuria to avoid the complications of nephrotic syndrome and to delay progression of kidney disease. Proteinuria remission is one of the most important independent predictors of kidney survival. Children with FSGS who do not achieve partial or complete remission have a 50% risk of progression to ESRD within 5 years whereas those who enter complete remission have a 5-year kidney survival rate of 90%. Treatment of idiopathic FSGS commonly involves immune-based and nonimmunologic therapy options. This manuscript will review the current state of FSGS therapy for children.
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Optimizing blood pressure control in patients with nondiabetic glomerular disease.
Umanath, K, Lewis, JB, Dwyer, JP
Advances in chronic kidney disease. 2014;(2):200-4
Abstract
Hypertension is a common problem among patients with glomerular disease and CKD. Optimal blood pressure targets for these patients have been the source of much debate. Careful review of the available data supports a blood pressure target of less than 140/90 mmHg. Consideration for a lower goal of less than 130/80 mmHg should be given for patients with heavy proteinuria. Renin-angiotensin system inhibitors should be used as the cornerstone of therapy for all patients with glomerular disease and CKD.
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8.
Sequential RAAS blockade: is it worth the risk?
Persson, F, Rossing, P
Advances in chronic kidney disease. 2014;(2):159-65
Abstract
Soon after the emergence of the renin-angiotensin-aldosterone system (RAAS) blocking treatment as the cornerstone of renoprotective treatment in the prevention and treatment of diabetic and nondiabetic CKD, it was investigated if a higher degree of achievable RAAS blockade by combining more than one compound is feasible and advantageous. Regardless of the benefits from using monotherapy for diabetic kidney disease, there is still much improvement to wish for in terms of kidney prognosis in these populations. A great deal of research has gone into evaluating combinations of the RAAS blocking treatments in different populations and with different drugs and doses. Studies have mostly been short-term and use surrogate endpoints such as albuminuria. Side effects have been well known and expected in terms of increasing potassium levels and hypotension, but to an acceptable extent. With recent disappointing results from major hard endpoint trials using dual RAAS blockade the concept is now under scrutiny. In this review we will discuss the pros and cons of dual RAAS blockade, with facts and findings from smaller studies, endpoint trials, and meta-analyses.
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9.
[Diastolic heart failure].
Wachter, R
Der Internist. 2014;(6):663-8
Abstract
BACKGROUND Heart failure with preserved ejection fraction (i.e. diastolic heart failure) accounts for about half of heart failure cases. The aim of this review is to reflect current knowledge regarding the epidemiology, pathophysiology and treatment. RESULTS Diastolic heart failure patients are principally elderly and predominantly female. Numerous pathophysiological alterations in this disease have been shown and recent therapeutic recommendations include control of cardiovascular risk factors and symptoms. New therapeutic options, such as inhibition of late sodium current, aldosterone receptor blockade, combined inhibition of AT1 receptor and the enzyme neprilysin, and phosphodiesterase 5 inhibition are discussed in this review and ongoing clinical trials are also briefly presented. CONCLUSION Diastolic heart failure remains a cardiac disease which is difficult to treat; however, new study results allow a better definition of a population of patients who could benefit from specific therapies.
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Azilsartan, aliskiren, and combination antihypertensives utilizing renin-angiotensin-aldosterone system antagonists.
Lanier, G, Sankholkar, K, Aronow, WS
American journal of therapeutics. 2014;(5):419-35
Abstract
Health care providers managing hypertension (HTN) have a large selection of pharmacologic agents to choose from, including several different classes of drugs and many similar drugs within each class. Antagonism of the renin-angiotensin-aldosterone system has been shown to be very effective for HTN, especially in patients with cardiovascular disease, diabetes, and heart failure. Within this group, there have been 2 new agents recently introduced to the US market and approved by the Food and Drug Administration. It is important for the HTN specialist to be familiar with the merits of these 2 drugs: the angiotensin receptor blocker Edarbi (azilsartan) and the renin inhibitor Tekturna (aliskiren). Additionally, there have been several new, fixed-dose combination antihypertensives introduced to the market since 2006 that use a renin-angiotensin-aldosterone antagonist. Seven of these combine 2 drugs together in a single pill: Edarbyclor (azilsartan/chlorthalidone), Exforge (amlodipine/valsartan), Azor (olmesartan/amlodipine), Twynsta (amlodipine/telmisartan), Tekturna HCT [aliskiren/hydrochlorothiazide (HCTZ)], Valturna (aliskiren/valsartan), Tekamlo (aliskiren/amlodipine). Three triple-drug combination medications have also been introduced recently: Exforge HCT (amlodipine/valsartan/HCTZ), Tribenzor (olmesartan/amlodipine/HCTZ), and Amturnide (aliskiren/amlodipine/hydrocholorothiazide). This review will summarize the trial data and important pharmacologic merits of these 2 new renin-angiotensin-aldosterone antagonists and the advantages of initiating treatment with one of the new fixed-dose, combination drugs approved over the last 5 years.