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Prevention and management of hyperkalemia in patients treated with renin-angiotensin-aldosterone system inhibitors.
Weinstein, J, Girard, LP, Lepage, S, McKelvie, RS, Tennankore, K
CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne. 2021;(48):E1836-E1841
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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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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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Overview of clinical use and side effect profile of valsartan in Chinese hypertensive patients.
Huang, QF, Li, Y, Wang, JG
Drug design, development and therapy. 2013;:79-86
Abstract
We reviewed the Chinese and English literature for the efficacy and safety data of valsartan monotherapy or combination therapy in Chinese hypertensive patients. According to the data of ten randomized controlled trials, valsartan monotherapy was as efficacious as another angiotensin receptor blocker or other classes of antihypertensive drugs, excepting the slightly inferior diastolic blood pressure-lowering effect in comparison with calcium channel blockers. According to the data of six randomized controlled trials, valsartan combination, with hydrochlorothiazide, amlodipine, or nifedipine gastrointestinal therapeutic system, was more efficacious than monotherapy of valsartan, amlodipine, or nifedipine gastrointestinal therapeutic system. According to these trials, valsartan had an acceptable tolerability, regardless of whether it was used as monotherapy or in combination therapy. Nonetheless, several rare side effects have been reported, indicating that it should still be used with caution. This is of particular importance given that there are millions of hypertensive patients, worldwide, currently exposed to the drug.
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Pharmacotherapy of heart failure with normal ejection fraction (HFNEF)--a systematic review.
Rajagopalan, S, Arora, A, Shafiq, N, Reddy S, S, Pandhi, P, Mittal, N, Malhotra, S
British journal of clinical pharmacology. 2011;(3):369-80
Abstract
AIM: The pharmacotherapy for heart failure with normal ejection fraction (HFNEF) is not as well defined as that for the treatment for heart failure with reduced ejection fraction (HFREF). Studies of the various drugs given for HFNEF have revealed conflicting results. The aim of this systematic review was to determine whether there is any benefit with pharmacotherapy in HFNEF in terms of cardiac outcomes. METHODS Electronic and printed sources were searched until August 2010 for randomized controlled clinical trials (RCTs) comparing drug therapy with placebo in HFNEF. Weighted mean difference and pooled odds ratio (OR) with 95% confidence intervals were calculated. RESULTS A total of six RCTs including 8410 patients with a mean follow-up period of 21 months were included in the analysis. Although there were no significant differences in all cause mortality between the two groups (pooled OR 0.95, 95% CI 0.79, 1.13, P= 0.55), the subgroup analysis revealed a slight but non significant advantage with the β-adrenoceptor blocker group. There was no significant difference between the two groups in terms of cardiovascular mortality, hospitalization, worsening heart failure, ejection fraction, E : A ratio, deceleration time and E : E' ratio. CONCLUSION There was no significant benefit of pharmacotherapy in HFNEF. This might have been because of a lack of stringent inclusion criteria for patients in the trials and lower power of the studies. Hence trials with well defined inclusion criteria, better power, longer follow-up periods and with echocardiographic parameters as endpoints are required to shed further light on this topic.
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Angiotensin blockade to reduce microvascular damage in diabetes mellitus.
Schmieder, RE, Martin, S, Lang, GE, Bramlage, P, Böhm, M
Deutsches Arzteblatt international. 2009;(34-35):556-62
Abstract
BACKGROUND Diabetic retinopathy and microalbuminuria are often thought of as distinct disease entities despite their common pathophysiology. Many studies have addressed the prognostic significance of these conditions and their treatment. METHODS Medline was selectively searched for articles published from 1948 to 2008 containing the terms "angiotensin," "microalbuminuria," and "retinopathy." The results were further amplified by screening the reference sections of the retrieved articles. RESULTS Diabetic retinopathy and microalbuminuria are expressions of microvascular damage. They are promoted by hypertension, hyperglycemia, dyslipidemia, and elevated levels of angiotensin II. They are treated by adjusting these risk factors to the near-normal range. In the IDNT study, angiotensin II blockade with irbesartan was found to lead to an absolute reduction of renal events by 7.4% as compared to standard treatment, and by 9.5% as compared to amlodipine. In the DIRECT study, candesartan reduced the progression of retinopathy by 13% and effected a regression by 34%. In the Steno-2 study, an intensive program of multifactorial risk reduction significantly lowered the rate of microvascular complications over a mean follow-up interval of 3.8 years (hazard ratios for different complications varying from 0.27 to 0.45). Over the longer term (13.3 years), this approach also led to a reduction of macrovascular events (HR 0.54 for mortality of all causes, 0.43 for cardiovascular mortality, and 0.41 for cardiovascular events). CONCLUSIONS Diabetic retinopathy and microalbuminuria are expressions of microvascular damage. They often appear together and point toward possible future macrovascular events. Multifactorial intervention can lessen the consequences of these pathological conditions.
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A combined role of calcium channel blockers and angiotensin receptor blockers in stroke prevention.
Wang, JG
Vascular health and risk management. 2009;:593-605
Abstract
Stroke is a leading cause of death and disability worldwide. The importance of lowering blood pressure for reducing the risk of stroke is well established. However, not all the benefits of antihypertensive treatments in stroke can be accounted for by reductions in BP and there may be differences between antihypertensive classes as to which provides optimal protection. Dihydropyridine calcium channel blockers, such as amlodipine, and angiotensin receptor blockers, such as valsartan, represent the two antihypertensive drug classes with the strongest supportive data for the prevention of stroke. Therefore, when combination therapy is required, a combination of these two antihypertensive classes represents a logical approach.
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Management of patients with nephrotic syndrome.
de Seigneux, S, Martin, PY
Swiss medical weekly. 2009;(29-30):416-22
Abstract
Nephrotic syndrome is characterised by proteinuria >3.5 g/24h, oedema, hypoalbuminaemia and hyperlipidaemia. Several glomerular diseases, either primary or secondary, may lead to nephrotic syndrome. Investigations for nephrotic syndrome include immunological and infectious evaluations. Renal biopsy is often mandatory, except in diabetes. Depending on aetiology specific treatment, often with immunosuppressive agents, may be implemented. In any cases nonspecific treatment should be started with ACE inhibitors or ARBs. Urinary protein loss leads to several complications: water and sodium retention, hyperlipidaemia, increased risk of thromboembolism and infection, anaemia and alteration of mineral metabolism. Each of these complications must be identified.
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Treating to protect: current cardiovascular treatment approaches and remaining needs.
Böhm, M, Werner, C, Jakobsen, A, Heroys, J, Ralph, A, Rees, T, Shaw, M
Medscape journal of medicine. 2008;(Supp):S3
Abstract
Current best practice to reduce cardiovascular disease involves evaluating patients' global cardiovascular risk profiles and devising treatment strategies accordingly. Despite the proven efficacy of this approach, very few physicians are adequately assessing risk, and consequently patients are failing to achieve desired treatment targets. Modifying lifestyle factors, such as diet, exercise, and cessation of smoking, remains one of the simplest and most potent means of reducing risk. Newly emerging evidence suggests that moderate physical activity (such as brisk walking for 30 minutes a day), eg, by raising levels of circulating endothelial progenitor cells, improves endothelial function and enhances vascular repair. However, patients remain remarkably reluctant to lifestyle changes, even in the face of overt, life-threatening disease. Statin treatment reduces cardiovascular morbidity and death in both primary and secondary prevention studies. However, over 90% of adults at high risk for coronary heart disease fail to achieve target low-density lipoprotein cholesterol levels in spite of statin therapy. Similarly, only about 37% of patients with hypertension meet blood pressure targets. Antihypertensive drugs achieve different levels of cardioprotection. Mounting evidence links regimens containing beta-blockers or diuretics with higher incidence of type 2 diabetes. In contrast, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers appear to confer extra protection on target organs on top of blood pressure reduction. The ONTARGET Trial Program is designed to clarify the importance of this effect. Educating patients, raising physicians' awareness, and implementing effective and safe treatment regimens are all necessary steps to bring about the much-needed improvements in cardiac health outcomes.
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The evolution of systolic blood pressure as a strong predictor of cardiovascular risk and the effectiveness of fixed-dose ARB/CCB combinations in lowering levels of this preferential target.
Mourad, JJ
Vascular health and risk management. 2008;(6):1315-25
Abstract
Elevated blood pressure is an important cardiovascular risk factor. Although targets for both diastolic blood pressure (DBP) and systolic blood pressure (SBP) are defined by current guidelines, DBP has historically taken precedence in hypertension management. However, there is strong evidence that SBP is superior to DBP as a predictor of cardiovascular events. Moreover, achieving control of SBP is assuming greater importance amongst an aging population. In spite of the growing recognition of the importance of SBP in reducing cardiovascular risk and the emphasis by current guidelines on SBP control, a substantial proportion of patients still fail to achieve SBP targets, and SBP control is achieved much less frequently than DBP control. Thus, new approaches to the management of hypertension are required in order to control SBP and minimize cardiovascular risk. Fixed-dose combination (FDC) therapy is an approach that offers the advantages of multiple drug administration and a reduction in regimen complexity that favors compliance. We have reviewed the latest evidence demonstrating the efficacy in targeting SBP of the most recent FDC products; combinations of the calcium channel blocker (CCB), amlodipine, with angiotensin receptor blockers (ARBs), valsartan or olmesartan. In addition, results from studies with new classes of agent are outlined.