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The Cochrane Database of Systematic... Feb 2017Eplerenone is an aldosterone receptor blocker that is chemically derived from spironolactone. In Canada, it is indicated for use as adjunctive therapy to reduce... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Eplerenone is an aldosterone receptor blocker that is chemically derived from spironolactone. In Canada, it is indicated for use as adjunctive therapy to reduce mortality for heart failure patients with New York Heart Association (NYHA) class II systolic chronic heart failure and left ventricular systolic dysfunction. It is also used as adjunctive therapy for patients with heart failure following myocardial infarction. Additionally, it is indicated for the treatment of mild and moderate essential hypertension for patients who cannot be treated adequately with other agents. It is important to determine the clinical impact of all antihypertensive medications, including aldosterone antagonists, to support their continued use in essential hypertension. No previous systematic reviews have evaluated the effect of eplerenone on cardiovascular morbidity, mortality, and magnitude of blood pressure lowering in patients with hypertension.
OBJECTIVES
To assess the effects of eplerenone monotherapy versus placebo for primary hypertension in adults. Outcomes of interest were all-cause mortality, cardiovascular events (fatal or non-fatal myocardial infarction), cerebrovascular events (fatal or non fatal strokes), adverse events or withdrawals due to adverse events, and systolic and diastolic blood pressure.
SEARCH METHODS
We searched the Cochrane Hypertension Specialised Register, CENTRAL, MEDLINE, Embase, and two trials registers up to 3 March 2016. We handsearched references from retrieved studies to identify any studies missed in the initial search. We also searched for unpublished data by contacting the corresponding authors of the included studies and pharmaceutical companies involved in conducting studies on eplerenone monotherapy in primary hypertension. The search had no language restrictions.
SELECTION CRITERIA
We selected randomized placebo-controlled trials studying adult patients with primary hypertension. We excluded studies in people with secondary or gestational hypertension and studies where participants were receiving multiple antihypertensives.
DATA COLLECTION AND ANALYSIS
Three review authors independently reviewed the search results for studies meeting our criteria. Three review authors independently extracted data and assessed trial quality using a standardized data extraction form. A fourth independent review author resolved discrepancies or disagreements. We performed data extraction and synthesis using a standardized format on Covidence. We conducted data analysis using Review Manager 5.
MAIN RESULTS
A total of 1437 adult patients participated in the five randomized parallel group studies, with treatment durations ranging from 8 to 16 weeks. The daily doses of eplerenone ranged from 25 mg to 400 mg daily. Meta-analysis of these studies showed a reduction in systolic blood pressure of 9.21 mmHg (95% CI -11.08 to -7.34; I = 58%) and a reduction of diastolic pressure of 4.18 mmHg (95% CI -5.03 to -3.33; I = 0%) (moderate quality evidence).There may be a dose response effect for eplerenone in the reduction in systolic blood pressure at doses of 400 mg/day. However, this finding is uncertain, as it is based on a single included study with low quality evidence. Overall there does not appear to be a clinically important dose response in lowering systolic or diastolic blood pressure at eplerenone doses of 50 mg to 400 mg daily. There did not appear to be any differences in the number of patients who withdrew due to adverse events or the number of patients with at least one adverse event in the eplerenone group compared to placebo. However, only three of the five included studies reported adverse events. Most of the included studies were of moderate quality, as we judged multiple domains as being at unclear risk in the 'Risk of bias' assessment.
AUTHORS' CONCLUSIONS
Eplerenone 50 to 200 mg/day lowers blood pressure in people with primary hypertension by 9.21 mmHg systolic and 4.18 mmHg diastolic compared to placebo, with no difference of effect between doses of 50 mg/day to 200 mg/day. A dose of 25 mg/day did not produce a statistically significant reduction in systolic or diastolic blood pressure and there is insufficient evidence for doses above 200 mg/day. There is currently no available evidence to determine the effect of eplerenone on clinically meaningful outcomes such as mortality or morbidity in hypertensive patients. The evidence available on side effects is insufficient and of low quality, which makes it impossible to draw conclusions about potential harm associated with eplerenone treatment in hypertensive patients.
Topics: Adult; Antihypertensive Agents; Blood Pressure; Eplerenone; Essential Hypertension; Female; Humans; Hypertension; Male; Middle Aged; Patient Dropouts; Randomized Controlled Trials as Topic; Spironolactone
PubMed: 28245343
DOI: 10.1002/14651858.CD008996.pub2 -
International Journal of Molecular... Jan 2024Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the... (Review)
Review
Primary aldosteronism (PA), a significant and curable cause of secondary hypertension, is seen in 5-10% of hypertensive patients, with its prevalence contingent upon the severity of the hypertension. The principal aetiologies of PA include bilateral idiopathic hypertrophy (BIH) and aldosterone-producing adenomas (APAs), while the less frequent causes include unilateral hyperplasia, familial hyperaldosteronism (FH) types I-IV, aldosterone-producing carcinoma, and ectopic aldosterone synthesis. This condition, characterised by excessive aldosterone secretion, leads to augmented sodium and water reabsorption alongside potassium loss, culminating in distinct clinical hallmarks: elevated aldosterone levels, suppressed renin levels, and hypertension. Notably, hypokalaemia is present in only 28% of patients with PA and is not a primary indicator. The association of PA with an escalated cardiovascular risk profile, independent of blood pressure levels, is notable. Patients with PA exhibit a heightened incidence of cardiovascular events compared to counterparts with essential hypertension, matched for age, sex, and blood pressure levels. Despite its prevalence, PA remains frequently undiagnosed, underscoring the imperative for enhanced screening protocols. The diagnostic process for PA entails a tripartite assessment: the aldosterone/renin ratio (ARR) as the initial screening tool, followed by confirmatory and subtyping tests. A positive ARR necessitates confirmatory testing to rule out false positives. Subtyping, achieved through computed tomography and adrenal vein sampling, aims to distinguish between unilateral and bilateral PA forms, guiding targeted therapeutic strategies. New radionuclide imaging may facilitate and accelerate such subtyping and localisation. For unilateral adrenal adenoma or hyperplasia, surgical intervention is optimal, whereas bilateral idiopathic hyperplasia warrants treatment with mineralocorticoid antagonists (MRAs). This review amalgamates established and emerging insights into the management of primary aldosteronism.
Topics: Humans; Aldosterone; Hyperplasia; Renin; Hypertension; Adrenocortical Adenoma; Hyperaldosteronism
PubMed: 38255973
DOI: 10.3390/ijms25020900 -
International Journal of Molecular... Mar 2023Aldosterone, a vital hormone of the human body, has various pathophysiological roles. The excess of aldosterone, also known as primary aldosteronism, is the most common... (Review)
Review
Aldosterone, a vital hormone of the human body, has various pathophysiological roles. The excess of aldosterone, also known as primary aldosteronism, is the most common secondary cause of hypertension. Primary aldosteronism is associated with an increased risk of cardiovascular disease and kidney dysfunction compared to essential hypertension. Excess aldosterone can lead to harmful metabolic and other pathophysiological alterations, as well as cause inflammatory, oxidative, and fibrotic effects in the heart, kidney, and blood vessels. These alterations can result in coronary artery disease, including ischemia and myocardial infarction, left ventricular hypertrophy, heart failure, arterial fibrillation, intracarotid intima thickening, cerebrovascular disease, and chronic kidney disease. Thus, aldosterone affects several tissues, especially in the cardiovascular system, and the metabolic and pathophysiological alterations are related to severe diseases. Therefore, understanding the effects of aldosterone on the body is important for health maintenance in hypertensive patients. In this review, we focus on currently available evidence regarding the role of aldosterone in alterations of the cardiovascular and renal systems. We also describe the risk of cardiovascular events and renal dysfunction in hyperaldosteronism.
Topics: Humans; Aldosterone; Cardiovascular Diseases; Hypertension; Hyperaldosteronism; Essential Hypertension
PubMed: 36982445
DOI: 10.3390/ijms24065370 -
Journal of Clinical Hypertension... Dec 2018Spectral Doppler ultrasonography provides the evaluation of renal resistive index (RRI), a noninvasive and reproducible measure to investigate arterial compliance and/or... (Review)
Review
Spectral Doppler ultrasonography provides the evaluation of renal resistive index (RRI), a noninvasive and reproducible measure to investigate arterial compliance and/or resistance. RRI seems to possess an important role in the evaluation of diverse cases of secondary hypertension. In essential hypertension, RRI is associated with subclinical markers of target organ damage and reflects renal disease progression beyond albuminuria and creatinine clearance. Also, RRI can estimate cardiovascular and renal risk. The evaluation of RRI may also help the therapeutic decisions. Given its simple assessment, RRI emerges as a simple method and a "multifunctional" tool that could help on the cardiovascular risk evaluation of the hypertensive patient.
Topics: Albuminuria; Blood Pressure; Cardiovascular Diseases; Clinical Decision-Making; Creatinine; Disease Progression; Female; Hemodynamics; Humans; Hypertension; Kidney; Kidney Diseases; Male; Risk Factors; Ultrasonography, Doppler; Vascular Resistance
PubMed: 30362245
DOI: 10.1111/jch.13410 -
Clinical Journal of the American... Mar 2017Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ... (Review)
Review
Despite improvements in hypertension awareness and treatment, 30%-60% of hypertensive patients do not achieve BP targets and subsequently remain at risk for target organ damage. This therapeutic gap is particularly important to nephrologists, who frequently encounter treatment-resistant hypertension in patients with CKD. Data are limited on how best to treat patients with CKD and resistant hypertension, because patients with CKD have historically been excluded from hypertension treatment trials. First, we propose a consistent definition of resistant hypertension as BP levels confirmed by both in-office and out-of-office measurements that exceed appropriate targets while the patient is receiving treatment with at least three antihypertensive medications, including a diuretic, at dosages optimized to provide maximum benefit in the absence of intolerable side effects. Second, we recommend that each patient undergo a standardized, stepwise evaluation to assess adherence to dietary and lifestyle modifications and antihypertensive medications to identify and reduce barriers and discontinue use of substances that may exacerbate hypertension. Patients in whom there is high clinical suspicion should be evaluated for potential secondary causes of hypertension. Evidence-based management of resistant hypertension is discussed with special considerations of the differences in approach to patients with and without CKD, including the specific roles of diuretics and mineralocorticoid receptor antagonists and the current place of emerging therapies, such as renal denervation and baroreceptor stimulation. We endorse use of such a systematic approach to improve recognition and care for this vulnerable patient group that is at high risk for future kidney and cardiovascular events.
Topics: Antihypertensive Agents; Coronary Vasospasm; Diet; Diuretics; Drug Therapy, Combination; Electric Stimulation Therapy; Humans; Hypertension; Life Style; Mineralocorticoid Receptor Antagonists; Patient Compliance; Renal Insufficiency, Chronic; Sympathectomy
PubMed: 27895136
DOI: 10.2215/CJN.06180616 -
Journal of the American College of... Oct 2022Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a... (Review)
Review
Several forms of secondary hypertension carry a high risk of cardiac morbidity and mortality. Evaluation of cardiac phenotypes in secondary hypertension provides a unique opportunity to study underlying hormonal and biochemical mechanisms affecting the heart. We review the characteristics of cardiac dysfunction in different forms of secondary hypertension and clarify the mechanisms behind the higher prevalence of heart damage in these patients than in those with primary hypertension. Attention to the specific clinical/biochemical phenotypes of these conditions may assist clinicians to screen for and confirm secondary forms of hypertension. Thereby, early signs of heart damage can be recognized and monitored, allowing individualized treatment to delay or prevent evolution toward more advanced disease.
Topics: Heart Failure; Heart Injuries; Humans; Hypertension; Phenotype
PubMed: 36202538
DOI: 10.1016/j.jacc.2022.08.714 -
International Journal of Molecular... Apr 2022Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most... (Review)
Review
Primary aldosteronism (PA) is a pathological condition characterized by an excessive aldosterone secretion; once thought to be rare, PA is now recognized as the most common cause of secondary hypertension. Its prevalence increases with the severity of hypertension, reaching up to 29.1% in patients with resistant hypertension (RH). Both PA and RH are "high-risk phenotypes", associated with increased cardiovascular morbidity and mortality compared to non-PA and non-RH patients. Aldosterone excess, as occurs in PA, can contribute to the development of a RH phenotype through several mechanisms. First, inappropriate aldosterone levels with respect to the hydro-electrolytic status of the individual can cause salt retention and volume expansion by inducing sodium and water reabsorption in the kidney. Moreover, a growing body of evidence has highlighted the detrimental consequences of "non-classical" effects of aldosterone in several target tissues. Aldosterone-induced vascular remodeling, sympathetic overactivity, insulin resistance, and adipose tissue dysfunction can further contribute to the worsening of arterial hypertension and to the development of drug-resistance. In addition, the pro-oxidative, pro-fibrotic, and pro-inflammatory effects of aldosterone may aggravate end-organ damage, thereby perpetuating a vicious cycle that eventually leads to a more severe hypertensive phenotype. Finally, neither the pathophysiological mechanisms mediating aldosterone-driven blood pressure rise, nor those mediating aldosterone-driven end-organ damage, are specifically blocked by standard first-line anti-hypertensive drugs, which might further account for the drug-resistant phenotype that frequently characterizes PA patients.
Topics: Aldosterone; Fibrosis; Humans; Hyperaldosteronism; Hypertension; Kidney
PubMed: 35563192
DOI: 10.3390/ijms23094803 -
American Journal of Hypertension Jun 2022Antihypertensive treatment is highly effective in both primary and secondary prevention of stroke. However, current guideline recommendations on the blood pressure goals...
Antihypertensive treatment is highly effective in both primary and secondary prevention of stroke. However, current guideline recommendations on the blood pressure goals in acute stroke are clinically empirical and generally conservative. Antihypertensive treatment is only recommended for severe hypertension. Several recent observational studies showed that the relationship between blood pressure and unfavorable clinical outcomes was probably positive in acute hemorrhagic stroke but J- or U-shaped in acute ischemic stroke with undetermined nadir blood pressure. The results of randomized controlled trials are promising for blood pressure management in hemorrhagic stroke but less so in ischemic stroke. A systolic blood pressure goal of 140 mm Hg is probably appropriate for acute hemorrhagic stroke. The blood pressure goal in acute ischemic stroke, however, is uncertain, and probably depends on the time window of treatment and the use of revascularization therapy. Further research is required to investigate the potential benefit of antihypertensive treatment in acute stroke, especially with regard to the possible reduction of blood pressure variability and more intensive blood pressure lowering in the acute and subacute phases of a stroke, respectively.
Topics: Antihypertensive Agents; Blood Pressure; Goals; Hemorrhagic Stroke; Humans; Hypertension; Ischemic Stroke; Stroke
PubMed: 35323883
DOI: 10.1093/ajh/hpac039 -
European Review For Medical and... Jul 2017Hypertension, one of the most common chronic and sporadic conditions, figures among the important worldwide public-health challenges, and it is a major risk for heart... (Review)
Review
Hypertension, one of the most common chronic and sporadic conditions, figures among the important worldwide public-health challenges, and it is a major risk for heart disease, stroke, kidney disease and other complications, including dementia. Hypertension is neglected by individuals, and the prevalence of this condition continues to rise across the world. A great number of patients receiving medical intervention is not successfully treated, while adequate curative health services are dependent on the exact update data of the countrywide prevalence of known and undetected cases. This renders elusive the possibility of a public strategy to eradicate hypertension. Accordingly, a global preventive approach in considering the known etiology of the disease established two types of cases hypertension including primary hypertension, which is idiopathic, and secondary hypertension, which is based on a demonstrable organic change in tissues. This is relevant since the secondary hypertension remains the most prevalent and it is associated with physical inactivity and bad nutrition. The environmental condition may be counteracting with an active life style. Physical exercise, which promotes hemodynamic and humoral changes in healthy subjects, may positively impact on hypertensive subjects. Indeed, patients with hypertension might improve their blood pressure, plasma lipoprotein-lipid profile, insulin sensitivity, likely to normotensive people, as well as the regression of the pathology of left ventricular hypertrophy. Exercise training is an important initial or adjunctive step that may be highly efficacious in the prevention and treatment of individuals with hypertension. Herein, we study the role of exercise training in the treatment of hypertension.
Topics: Exercise; Humans; Hypertension; Life Style
PubMed: 28770948
DOI: No ID Found -
Journal of Clinical Hypertension... Sep 2022Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive... (Review)
Review
Arterial hypertension is a major risk factor for cardiovascular disease. The prevalence of primary aldosteronism (PA) ranges from 5% to 10% in the general hypertensive population and is regarded as one of the most common causes of secondary hypertension. There are two major causes of PA: bilateral adrenal hyperplasia and aldosterone-producing adenoma. The diagnosis of PA comprises screening, confirmatory testing, and subtype differentiation. The Endocrine Society Practice Guidelines for the diagnosis and treatment of PA recommends screening of patients at an increased risk of PA. These categories include patients with stage 2 and 3 hypertension, drug-resistant hypertension, hypertensive with spontaneous or diuretic-induced hypokalemia, hypertension with adrenal incidentaloma, hypertensive with a family history of early onset hypertension or cerebrovascular accident at a young age, and all hypertensive first-degree relatives of patients with PA. Recently, several studies have linked PA with obstructive sleep apnea and atrial fibrillation unexplained by structural heart defects and/or other conditions known to cause the arrhythmia, which may be partly responsible for the higher rates of cardiovascular and cerebrovascular accidents in patients with PA. The aim of this review is to discuss which patients should be screened for PA, focusing not only on well-established guidelines but also on additional groups of patients with a potentially higher prevalence of PA, as has been reported in recent research.
Topics: Adrenal Gland Neoplasms; Aldosterone; Diuretics; Humans; Hyperaldosteronism; Hypertension; Renin
PubMed: 36196469
DOI: 10.1111/jch.14558