Aldosterone Antagonists In Patients Research Articles

Medical Therapy for Systemic Right Ventricles: A Systematic Review (Part 1) for the 2018 AHA/ACC Guideline for the Management of Adults With Congenital Heart Disease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines.

Patients with systemic morphological right ventricles (RVs), including congenitally corrected transposition of the great arteries and dextro-transposition of the great arteries with a Mustard or Senning atrial baffle repair, have a high likelihood of developing systemic ventricular dysfunction. Unfortunately, there are a limited number of clinical studies on the efficacy of medical therapy for systemic RV dysfunction. We performed a systematic review and meta-analysis to assess the effect of angiotensin-converting enzyme (ACE) inhibitors, angiotensin-receptor blockers (ARBs), beta blockers, and aldosterone antagonists in adults with systemic RVs. The inclusion criteria included age ≥18 years, systemic RVs, and at least 3 months of treatment with ACE inhibitor, ARB, beta blocker, or aldosterone antagonist. The outcomes included RV end-diastolic and end-systolic dimensions, RV ejection fraction, functional class, and exercise capacity. EMBASE, PubMed, and Cochrane databases were searched. The selected data were pooled and analyzed with the DerSimonian-Laird random-effects meta-analysis model. Between-study heterogeneity was assessed with Cochran's Q test. A Bayesian meta-analysis model was also used in the event that heterogeneity was low. Bias assessment was performed with the Newcastle-Ottawa Scale and Cochrane Risk of Bias Tool, and statistical risk of bias was assessed with Begg and Mazumdar's test and Egger's test. Six studies met the inclusion criteria, contributing a total of 187 patients; treatment with beta blocker was the intervention that could not be analyzed because of the small number of patients and diversity of outcomes reported. After at least 3 months of treatment with ACE inhibitors, ARBs, or aldosterone antagonists, there was no statistically significant change in mean ejection fraction, ventricular dimensions, or peak ventilatory equivalent of oxygen. The methodological quality of the majority of included studies was low, mainly because of a lack of a randomized and controlled design, small sample size, and incomplete follow-up. In conclusion, pooled results across the limited available studies did not provide conclusive evidence with regard to a beneficial effect of medical therapy in adults with systemic RV dysfunction. Randomized controlled trials or comparative-effectiveness studies that are sufficiently powered to demonstrate effect are needed to elucidate the efficacy of ACE inhibitors, ARBs, beta blockers, and aldosterone antagonists in patients with systemic RVs.

Aldosterone Antagonist Therapy and Mortality in Patients With ST-Segment Elevation Myocardial Infarction Without Heart Failure

Treatment with aldosterone antagonists is recommended and has been shown to have beneficial effects in patients with ST-segment elevation myocardial infarction (STEMI) and left ventricular ejection fraction (LVEF) less than 40%. However, the role of aldosterone antagonists in patients with ejection fraction greater than 40% or without congestive heart failure is not well known. To perform a systematic review and meta-analysis using standard techniques to determine the role of therapy with aldosterone antagonists in this patient population. PubMed, Embase, CINAHL, and Cochrane Central databases were searched and a manual search for relevant references from the selected articles and published reviews was performed from database inception through June 2017. Randomized clinical trials that evaluated treatment with aldosterone antagonists in patients with STEMI without clinical heart failure or LVEF greater than 40% were included. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were used to conduct and report the meta-analysis, which used a random-effects model. Two investigators independently performed the database search and agreed on the final study selection. A manual search was performed for relevant references from the selected articles and published reviews. The outcomes analyzed were mortality, new congestive heart failure, recurrent myocardial infarction, ventricular arrhythmia, and changes in LVEF, serum potassium level, and creatinine level at follow-up. In all, 10 randomized clinical trials with a total of 4147 unique patients were included in the meta-analysis. In patients who presented with STEMI without heart failure, treatment with aldosterone antagonists compared with control was associated with lower risk of mortality (2.4% vs 3.9%; odds ratio [OR], 0.62; 95% CI, 0.42-0.91; P = .01) and similar risks of myocardial infarction (1.6% vs 1.5%; OR, 1.03; 95% CI, 0.57-1.86; P = .91), new congestive heart failure (4.3% vs 5.4%; OR, 0.82; 95% CI, 0.56-1.20; P = .31), and ventricular arrhythmia (4.1% vs 5.1%; OR, 0.76; 95% CI, 0.45-1.31; P = .33). Similarly, treatment with aldosterone antagonists compared with control was associated with a small yet significant increase in LVEF (mean difference, 1.58%; 95% CI, 0.18%-2.97%; P = .03), a small increase in serum potassium level (mean difference, 0.07 mEq/L; 95% CI, 0.01-0.13 mEq/L; P = .02), and no change in serum creatinine level (standardized mean difference, 1.4; 95% CI, -0.43 to 3.24; P = .13). Treatment with aldosterone antagonists is associated with a mortality benefit in patients with STEMI with LVEF greater than 40% or without heart failure.

CLINICAL EFFECTIVENESS OF SPIRONOLACTONE IN HOSPITALIZED OLDER ELIGIBLE (EF LESS THAN OR EQUAL TO 35% AND EGFR GREATER THAN OR EQUAL TO 30 ML/MIN/1.73 M2) PATIENTS WITH HEART FAILURE

Background: Randomized controlled trials have established the efficacy of aldosterone antagonists in patients with heart failure and reduced ejection fraction (HFrEF). However, there is limited evidence of their clinical effectiveness in real-world eligible patients with HFrEF (PMID: 23188026). We

Use of Aldosterone Antagonists for Treatment of Uncontrolled Resistant Hypertension

Multiple studies indicate that primary aldosteronism (PA) is common in patients with resistant hypertension, with an estimated prevalence of approximately 20%. Additional studies suggest that beyond this 20% of patients with classical PA, there is a larger proportion of patients with lesser degrees of hyperaldosteronism which contributes even more broadly to antihypertensive treatment resistance. Given these observations, it is intuitive that use of aldosterone antagonists will provide antihypertensive benefit in patients with resistant hypertension and evidence of aldosterone excess. Intriguingly, however, are clinical findings demonstrating substantive benefit of aldosterone antagonists in patients with resistant hypertension, but without demonstrative evidence of hyperaldosteronism, that is, with seemingly normal or even low aldosterone levels. Spironolactone is clearly established as the most effective fourth agent for treatment of uncontrolled resistant hypertension. Emerging observations suggest a further role of spironolactone for counteracting the effects of diet high in sodium, particularly in obese, hypertensive patients.

Spironolactone for resistant hypertension—hard to resist?

Spironolactone for resistant hypertension—hard to resist?

The Effects of Aldosterone Antagonists in Patients With Resistant Hypertension: A Meta-Analysis of Randomized and Nonrandomized Studies.

A few studies have shown aldosterone antagonists (AA) to be effective therapy in patients with resistant hypertension (RH). We performed a meta-analysis of randomized and nonrandomized studies of AA in patients with RH. We searched PUBMED, EMBASE, and CENTRAL for studies on the use of AA in patients with RH. Meta-analysis was performed using random-effects model. The change in office and ambulatory blood pressures (BP), effects on biochemical profile, change in the number of antihypertensive agents, and adverse events were main outcomes. We included 15 studies (3 randomized controlled trials, 1 nonrandomized comparative study, and 11 single-arm studies) with 1,204 total patients in the meta-analysis. In comparative studies, AA reduced systolic BP (SBP) by 24.26 mm Hg (95% CI: 8.65-39.87, P = 0.002) and diastolic BP (DBP) by 7.79 mm Hg (3.79-11.79, P = 0.0001). Similarly, AA reduced SBP by 22.74 mm Hg (18.21-27.27, P < 0.00001) and DBP by 10.49 mm Hg (8.85-12.13, P < 0.00001) in single-arm studies. AA resulted in significant change in serum electrolytes in single-arm studies but not in comparative studies. Significantly more adverse events were noted in single-arm studies but not in comparative studies. On the basis of the current meta-analysis, we conclude that AA is safe and effective therapy in patients with RH.

Factors associated with resistant hypertension in a large cohort of hypertensive patients: the Pol-Fokus study.

Patients with resistant hypertension (RHT) are at high risk for coronary artery disease (CAD) and cerebrovascular disease (CVD), compared with the general hypertensive population. The aim of the study was to evaluate factors associated with RHT in a large sample of hypertensive patients under the care of general practitioners and specialists in Poland. We included 12 375 patients (mean age, 64.0 ±12.3 years; age range, 18-98 years; women, 59%) with hypertension treated for at least 1 year. Patients were divided into 3 groups: with controlled hypertension, uncontrolled hypertension (not fulfilling the criteria for RHT), and RHT. Controlled hypertension, uncontrolled hypertension, and RHT were found in 47.3%, 27.9%, and 24.7% of the patients, respectively. The RHT rate was higher in patients visiting specialist offices (29.8%) and in patients with diabetes (32.5%), CAD (31.5%), CVD (33.3%), and impaired renal function (31.9%). Patients with RHT were characterized by the highest rate of high (23.5%) and very high (60.5%) added cardiovascular risk. An underuse of preferred antihypertensive drug combinations and aldosterone antagonists in patients with uncontrolled hypertension and RHT was observed. In a multivariate analysis, RHT was independently associated with male sex, higher pulse pressure, metabolic syndrome, diabetes, CAD, CVD, diseases requiring treatment with nonsteroidal anti-inflammatory drugs and an estimated glomerular filtration rate of less than 60 ml/min/1.73 m2. The vast majority of patients with RHT carry a high or very high cardiovascular risk. In addition, the underuse of preferred antihypertensive drug combinations and aldosterone antagonists has been observed.

The use of an aldosterone antagonist in a patient with chronic kidney disease

Mr CR has heart failure and chronic kidney disease (CKD). He visits the GP with shortness of breath and fatigue and, suspecting his heart failure has worsened, the GP prescribes spironolactone. Adrian Coleman and Mee Onn Chai discuss the use of this aldosterone antagonist in patients with CKD.

Prognostic Impacts of Aldosterone Antagonists in Patients with Heart Failure with Preserved Ejection Fraction-A Report from the CHART-2 Study

Prognostic Impacts of Aldosterone Antagonists in Patients with Heart Failure with Preserved Ejection Fraction-A Report from the CHART-2 Study

Gap between clinical guidelines and practice: The case of aldosterone-antagonists in patients with myocardial infarction

Gap between clinical guidelines and practice: The case of aldosterone-antagonists in patients with myocardial infarction

New Heart Failure Guidelines Improve Prognosis, Quality of Life

New Heart Failure Guidelines Improve Prognosis, Quality of Life

Additional use of an aldosterone antagonist in patients with mild to moderate chronic heart failure: a systematic review and meta‐analysis

Aldosterone antagonists (AldoAs) have been used to treat severe chronic heart failure (CHF). There is uncertainty regarding the efficacy of using AldoAs in mild to moderate CHF with New York Heart Association (NYHA) classifications of I to II. This study summarizes the evidence for the efficacy of spironolactone (SP), eplerenone (EP) and canrenone in mild to moderate CHF patients. PubMed, MEDLINE, EMBASE and OVID databases were searched before June 2012 for randomized and quasi-randomized controlled trials assessing AldoA treatment in CHF patients with NYHA classes I to II. Data concerning the study's design, patients' characteristics and outcomes were extracted. Risk ratio (RR) and weighted mean differences (WMD) or standardized mean difference were calculated using either fixed or random effects models. Eight trials involving 3929 CHF patients were included. AldoAs were superior to the control in all cause mortality (RR 0.79, 95% CI 0.66, 0.95) and in re-hospitalization for cardiac causes (RR 0.62, 95% CI 0.52, 0.74), the left ventricular ejection fraction was improved by AldoA treatment (WMD 2.94%, P = 0.52). Moreover, AldoA therapy decreased the left ventricular end-diastolic volume (WMD -14.04 ml, P < 0.00001), the left ventricular end-systolic volume (WMD -14.09 ml, P < 0.00001). A stratified analysis showed a statistical superiority in the benefits of SP over EP in reducing LVEDV and LVESV. AldoAs reduced B-type natriuretic peptide concentrations (WMD -37.76 pg ml(-1), P < 0.00001), increased serum creatinine (WMD 8.69 μmol l(-1), P = 0.0003) and occurrence of hyperkalaemia (RR 1.78, 95% CI 1.43, 2.23). Additional use of AldoAs in CHF patients may decrease mortality and re-hospitalization for cardiac reasons, improve cardiac function and simultaneously ameliorate LV reverse remodelling.

What Are the Benefits of Aldosterone Antagonists in Real-World HF Treatment?

Despite trial evidence of the efficacy of aldosterone antagonists in patients with heart failure (HF), such agents are used in a minority of HF

When Conventional Heart Failure Therapy is Not Enough: Angiotensin Receptor Blocker, Direct Renin Inhibitor, or Aldosterone Antagonist?

In patients on conventional heart failure therapy including angiotensin-converting enzyme (ACE) inhibitors, the addition of angiotensin receptor blockers (ARBs), direct renin inhibitors (DRIs), or aldosterone antagonists are therapeutic options to further reduce the risk of cardiovascular events. However, whether one is preferable over the other is not known. PubMed, EMBASE, and Cochrane Central Register of Controlled Trials databases were searched for randomized clinical trials (RCTs), until March 2011, of trials testing either an ARB, DRI, or an aldosterone antagonist in patients with heart failure who were on conventional heart failure therapy with follow-up of at least 3 months. Efficacy (death, cardiovascular death, nonfatal myocardial infarction, heart failure hospitalization and composite of cardiovascular death or heart failure hospitalization) and safety (hyperkalemia, hypotension, renal failure) outcomes were compared. The authors identified 16 RCTs involving 31,429 participants that satisfied the inclusion criteria. When compared with placebo (reference rate ratio [RR] of 1), aldosterone antagonists reduced the rate of death (RR, 0.79; 95% credibility interval [CrI], 0.66-0.98), cardiovascular death (RR, 0.78; 95% CrI, 0.65-0.93), heart failure hospitalization (RR, 0.74; 95% CrI, 0.55-0.94), and the composite of cardiovascular death or heart failure hospitalization (RR, 0.73; 95% CrI, 0.55-0.90) with no difference for other efficacy outcomes. However, ARBs and DRIs did not result in any significant reduction in the rate of any of the efficacy outcomes when compared with placebo. When compared with placebo (RR=1), ARBs increased the rate of hyperkalemia (138% increase), renal failure (126% increase), and hypotension (63% increase). Similarly, aldosterone antagonists resulted in a 110% increase in hyperkalemia and DRIs with a 98% increase in hypotension. In patients with heart failure and reduced systolic function on conventional heart failure medications, the risk benefit ratio favors the addition of aldosterone antagonists over ARBs or DRIs.

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Section 5: Management of Asymptomatic Patients with Reduced Left Ventricular Ejection Fraction

Aldosterone Antagonists in Patients With Heart Failure—Reply

Aldosterone Antagonists in Patients With Heart Failure—Reply

Sodium Retention in Heart Failure and Cirrhosis

Patients with cirrhosis and heart failure (HF) share the pathophysiology of decreased effective arterial blood volume because of splanchnic vasodilatation in cirrhosis and decreased cardiac output in HF, with resultant stimulation of the renin-angiotensin-aldosterone system. Hyperaldosteronism plays a major role in the pathogenesis of ascites and contributes to resistance to loop diuretics. Therefore, the use of high doses of aldosterone antagonist (spironolactone up to 400 mg/day) is the main therapy to produce a negative sodium balance in cirrhotic patients with ascites. Hyperaldosteronism also has increasingly been recognized as a risk factor for myocardial and vascular fibrosis. Therefore, low-dose aldosterone antagonists are being used in patients with HF for cardioprotective action. However, the doses (25 to 50 mg/day) at which they are being used in cardiac patients as reported in the Randomized Aldactone Evaluation Study are not natriuretic. It is likely, therefore, that the mortality benefit relates primarily from their effect on cardiac and vascular fibrosis. Resistance to commonly used loop diuretics is frequently present in patients with advanced HF. In patients with decompensated HF with volume overload who are loop diuretic resistant, ultrafiltration may be the only available option. This is, however, an invasive procedure. For these patients, natriuretic doses of aldosterone antagonists (spironolactone >50 mg/day) may be a potential option. The competitive natriuretic response of aldosterone antagonists is related to activity of the renin-angiotensin-aldosterone system: the higher the renin-angiotensin-aldosterone system activity, the higher the dose of aldosterone antagonist required to produce natriuresis. This article will discuss the potential use of natriuretic doses of aldosterone antagonists in patients with HF, including the potential side effect of hyperkalemia.

Comorbidities in heart failure: a key issue

Comorbidities in heart failure: a key issue

Uncertainty on the Use of Aldosterone Antagonists for Primary Therapy for Sudden Cardiac Death in the Setting of Implanted Devices

In the early development of therapy for acute myocardial infarction, it was thought that once the necrotic process had been completed (usually within 24 hours of coronary artery occlusion), additional therapies could not affect outcome. However, after completion of the necrotic process, the myocardial infarction may thin and stretch (involving lengthwise slippage of myocytes), a phenomenon referred to as myocardial infarct expansion. This process causes local left ventricular cavity dilatation followed by gradual global left ventricular dilatation and lengthwise (eccentric) hypertrophy of the noninfarcted tissue. Apoptosis (programmed cell death) and some attempt of the myocardium to regenerate, especially at the infarct border zone, may also contribute to this remodeling process of the ventricle. If the left ventricle remodels in such a way that it becomes very dilated, then the prognosis is poor, and heart failure is more likely to occur.1 These later processes of myocardial infarct expansion and left ventricular remodeling became the target of therapies such as angiotensin-converting enzyme (ACE) inhibition that could be initiated after 24 hours of coronary occlusion. ACE inhibition, angiotensin receptor blockade, and long-term β-blockade have become standard pharmacological approaches for postinfarction left ventricular dysfunction and heart failure. Response by Pitt and Pitt p 2989 Ventricular arrhythmias can occur in both the acute and chronic phases of acute myocardial infarction and can lead to sudden cardiac death (SCD). Reentrant arrhythmias may arise at the border zone of infarcts, causing monomorphic ventricular tachycardia that may occur years after the index infarction. Recurrent myocardial ischemia resulting in an unstable substrate may contribute to polymorphic ventricular tachycardia or ventricular fibrillation. Agents such as β-blockers that are anti-ischemic may reduce sudden death by quieting this unstable substrate. In the Multicenter Automatic Defibrillator Implantation Trial (MADIT) II, implantable defibrillators were shown to reduce mortality in post–myocardial infarction patients with …

Aldosterone and Resistant Hypertension

Refractory or resistant hypertension, defined as the failure to control systolic ( < 140 mmHg) and/or diastolic blood pressure ( < 90 mmHg) despite the use of three or more different classes of antihypertensive agents, is a common problem in clinical practice. Several factors induce treatment resistance, especially secondary hypertension, such as primary aldosteronism. Some authors have argued for a direct role of aldosterone autonomy as a mechanism for drug resistance and have recommended the search for primary aldosteronism in cases of severe or resistant hypertension. This proposal is further supported by the demonstration of antihypertensive efficacy of aldosterone antagonists in patients with refractory hypertension. Recently, we have demonstrated a direct role of aldosterone excess as a mechanism for drug resistance, since patients with elevated aldosterone plasma levels develop resistant hypertension, even in the absence of clinically diagnosed primary aldosteronism. The mechanism of resistance may be ascribed to increased plasma volume, regardless of renal function, and cardiovascular remodeling. The present review highlights the role of aldosterone excess as a cause of treatment resistance beyond true primary aldosteronism and provides a conceptual framework for the use of aldosterone antagonists in patients with resistant hypertension.