scholarly journals Angiotensin Receptor Antagonists to Prevent Sudden Death in Heart Failure: Does the Dose Matter?

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Pietro Francia ◽  
Francesca Palano ◽  
Giuliano Tocci ◽  
Carmen Adduci ◽  
Agnese Ricotta ◽  
...  
Keyword(s):  
Randomized Clinical Trials ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Pharmacological Therapy ◽  
Angiotensin Receptor ◽  
Icd Implantation ◽  
Severe Left Ventricular Dysfunction ◽  
The Impact

International guidelines recommend ICD implantation in patients with severe left ventricular dysfunction of any origin only after careful optimization of medical therapy. Indeed, major randomized clinical trials suggest that suboptimal use of fundamental drugs, such as ACE inhibitors (ACE-i) and beta-blockers, may affect ICD shock-free survival, sudden cardiac death (SCD), and overall mortality. While solid evidence in favour of pharmacological therapy based on ACE-i with or without beta-blockers is available, data on SCD in HF patients treated with angiotensin receptor blockers (ARBs) are limited. The present paper systematically analyses the impact of ARBs on SCD in HF and reviews the contributory role of the renin-angiotensin system (RAS) to the establishment of arrhythmic substrates. The following hypothesis is supported: (1) the RAS is a critical component of the electrical remodelling of the failing myocardium, (2) RAS blockade reduces the risk of SCD, and (3) ARBs represent a powerful tool to improve overall survival and possibly reduce the risk of SCD provided that high doses are employed to achieve optimal AT1-receptor blockade.

scholarly journals Comparative analysis of telmisartan and olmesartan on cardiac function in the transgenic (mRen2)27 rat

2011 ◽  
Vol 300 (1) ◽  
pp. H181-H190 ◽  
Author(s):  
Vincent G. DeMarco ◽  
Megan S. Johnson ◽  
Javad Habibi ◽  
Lakshmi Pulakat ◽  
Rukhsana Gul ◽  
...  
Keyword(s):  
Angiotensin Receptor Blockers ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Stroke Work ◽  
Angiotensin Receptor ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ppar Γ ◽  
System Activation

Telmisartan, an angiotensin receptor blocker, may have unique benefits as it possesses partial peroxisome proliferator-activated receptor (PPAR)-γ agonist activity in addition to antihypertensive effects. In this study, we test whether treatment with telmisartan ameliorates cardiovascular abnormalities to a greater extent than olmesartan, which has little PPAR-γ activity. The hypertensive rodent model of tissue renin-angiotensin system activation, transgenic (mRen2)27 (Ren2) rats and their littermate Sprague-Dawley controls were used. Rats were treated with telmisartan (2 mg·kg−1·day−1), olmesartan (2.5 mg·kg−1·day−1), or vehicle via drinking water for 3 wk; these doses achieved similar blood pressure control, as measured by telemetry. Ren2 rats displayed impaired diastolic and systolic function using left ventricular (LV) pressure-volume (P-V) analysis. Load-independent diastolic indexes, including the time constant of isovolumic relaxation and the slope of the end-diastolic P-V relationship, as well as systolic indexes, including preload recruitable stroke work, the dP/d tmax-end-diastolic volume (EDV) relationship, and the P-V area-EDV relationship, were elevated in Ren2 rats compared with Sprague-Dawley controls ( P < 0.05). The Ren2 myocardium exhibited parallel increases in the oxidant markers NADPH oxidase and 3-nitrotyrosine. The increase in the prohypertrophic protein Jak2 in Ren2 rats was associated with cardiac structural abnormalities using light microscopic and ultrastructural analysis, which included interstitial fibrosis, cardiomyocyte and LV hypertrophy, and mitochondrial derangements. Both angiotensin receptor blockers attenuate these abnormalities to a similar extent. Our data suggest that the beneficial effect of telmisartan and olmesartan on cardiac structure and function may be predominantly pressor-related or angiotensin type 1 receptor dependent in this model of renin-angiotensin system activation.

scholarly journals Cardiorenal Systems Modeling: Left Ventricular Hypertrophy and Differential Effects of Antihypertensive Therapies on Hypertrophy Regression

2021 ◽  
Vol 12 ◽  
Author(s):  
K. Melissa Hallow ◽  
Charles H. Van Brackle ◽  
Sommer Anjum ◽  
Sergey Ermakov
Keyword(s):  
Renal Function ◽  
Cardiac Remodeling ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Pressure Overload ◽  
Volume Overload ◽  
Left Ventricular ◽  
Angiotensin Receptor ◽  
Organ Systems ◽  
Receptor Blockers

Cardiac and renal function are inextricably connected through both hemodynamic and neurohormonal mechanisms, and the interaction between these organ systems plays an important role in adaptive and pathophysiologic remodeling of the heart, as well as in the response to renally acting therapies. Insufficient understanding of the integrative function or dysfunction of these physiological systems has led to many examples of unexpected or incompletely understood clinical trial results. Mathematical models of heart and kidney physiology have long been used to better understand the function of these organs, but an integrated model of renal function and cardiac function and cardiac remodeling has not yet been published. Here we describe an integrated cardiorenal model that couples existing cardiac and renal models, and expands them to simulate cardiac remodeling in response to pressure and volume overload, as well as hypertrophy regression in response to angiotensin receptor blockers and beta-blockers. The model is able to reproduce different patterns of hypertrophy in response to pressure and volume overload. We show that increases in myocyte diameter are adaptive in pressure overload not only because it normalizes wall shear stress, as others have shown before, but also because it limits excess volume accumulation and further elevation of cardiac stresses by maintaining cardiac output and renal sodium and water balance. The model also reproduces the clinically observed larger LV mass reduction with angiotensin receptor blockers than with beta blockers. We further provide a mechanistic explanation for this difference by showing that heart rate lowering with beta blockers limits the reduction in peak systolic wall stress (a key signal for myocyte hypertrophy) relative to ARBs.

scholarly journals Impact of angiotensin receptor blocker product recalls on antihypertensive prescribing in Germany

2020 ◽  
Author(s):  
Ulrike Maria Rudolph ◽  
Salka Enners ◽  
Marita Kieble ◽  
Felix Mahfoud ◽  
Michael Böhm ◽  
...  
Keyword(s):  
Antihypertensive Drugs ◽  
Beta Blockers ◽  
Angiotensin Receptor Blockers ◽  
Fourth Quarter ◽  
Fixed Dose ◽  
Channel Blockers ◽  
Product Recalls ◽  
Angiotensin Receptor ◽  
Defined Daily Doses ◽  
The Impact

Abstract In Germany, ~8 million patients take angiotensin receptor blockers (ARBs) and 2.25 million of them valsartan. In 2018, contamination of generic ARBs with probable carcinogenic nitrosamines resulted in more than 30 recalls. The impact of such a huge recall has never been explored in Europe. We analyzed the utilization of valsartan, all ARBs, and other alternative antihypertensive drugs in Germany. We used our database of anonymized dispensing data from >80% of community pharmacies at the expense of the statutory health insurance (SHI) funds from January 2017 to December 2019. We analyzed 290.8 million prescriptions, including all oral mono- and fixed-dose combinations of ARBs and plausible alternatives, i.e. ACE inhibitors (ACEi), beta-blockers (BB), and calcium channel blockers (CCB). Utilization was calculated by defined daily doses per 1000 SHI-insured persons per day (DID). Valsartan use decreased substantially after the recalls in July 2018 from 39.0 to 14.2 DID (−64%) in the second quarter of 2019 and to 16.9 DID (−57%) in the fourth quarter of 2019. Simultaneously, the use of alternative ARBs increased from 77.7 DID in the second quarter of 2018 to 121.9 DID (+57%) in the fourth quarter of 2019, mainly due to an increase of candesartan dispensing to 99.8 DID (+73%). There were no changes in the utilization of ACEi, BB, or CCB. The majority of recalled generic valsartan products were replaced by other ARBs, predominantly candesartan, despite documented drug shortages. In contrast to previous safety warnings/recalls, our data do not suggest an under-prescription of antihypertensives during this period.

Abstract 2391: Impact of Therapies for Anemia on Outcomes in Patients with Heart Failure in Randomized Clinical Trials

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Howard M Julien ◽  
Preetika Muthukrishnan ◽  
Eldrin F Lewis
Keyword(s):  
Heart Failure ◽  
Clinical Trials ◽  
Ejection Fraction ◽  
Serum Creatinine ◽  
Exercise Capacity ◽  
Randomized Clinical Trials ◽  
Meta Analysis ◽  
Left Ventricular ◽  
Left Ventricular Ejection ◽  
The Impact

Anemia is common in heart failure (HF) patients and has been well-established as a risk factor for increased risk of HF hospitalization and mortality. Treatment with erythropoietin stimulating agents (ESA) has increased hemoglobin, but outcomes trials are limited and use of ESA has been controversial given disparate results in other populations. This meta-analysis aimed to evaluate the impact of ESA and iron on outcomes in HF patients. A systematic review of four databases was conducted in April 2008 (n = 95 unique trials). Analysis inclusion criteria included randomized controlled trial to ESA/iron with clinically defined HF, yielding 10 eligible trials published between 6/01–3/08. Data was independently extracted and cross-checked for accuracy and reliability (2 investigators). A total of 768 subjects (421 treated and 338 controls) are included (Characteristics in Table 1 ). Randomization to ESA produced a significant improvement in exercise capacity 0.39 standard units [95% CI 0.1– 0.6, p = 0.001], a 5.72% [95% CI 1.2–10.3, p = 0.014] increase in left ventricle ejection fraction and a 0.23 mg/dL [95% CI 0.4 – 0.1 p = 0.001] reduction in serum creatinine. There was no difference in all-cause mortality - RR 0.79 [95% CI 0.49, 1.26, p = 0.320]. Trends were noted in reduced hospitalization rates, decreased brain natriuretic peptide, and improved quality of life. Meta-analysis of randomized studies of treatment of anemia in HF patients suggests significant benefit in exercise capacity, left ventricular ejection fraction, and serum creatinine. There does not appear to be excess mortality with ESA/iron treatment. Despite favorable findings, definitive randomized clinical trials are needed to assess the role of this treatment modality in HF management. Table 1. Baseline Patient and Study Characteristics

scholarly journals Control of blood pressure and cardiovascular outcomes in type 2 diabetes

Open Medicine ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. 304-323 ◽  
Author(s):  
Hernando Vargas-Uricoechea ◽  
Manuel Felipe Cáceres-Acosta
Keyword(s):  
Blood Pressure ◽  
Cardiovascular Events ◽  
Angiotensin Receptor Blockers ◽  
Pharmacological Therapy ◽  
Current Evidence ◽  
Diabetic Patients ◽  
Channel Blockers ◽  
Converting Enzyme Inhibitors ◽  
Patients With Diabetes ◽  
The Impact

AbstractHigh blood pressure in patients with diabetes mellitus results in a significant increase in the risk of cardiovascular events and mortality. The current evidence regarding the impact of intervention on blood pressure levels (in accordance with a specific threshold) is not particularly robust. Blood pressure control is more difficult to achieve in patients with diabetes than in non-diabetic patients, and requires using combination therapy in most patients. Different management guidelines recommend initiating pharmacological therapy with values >140/90 mm/Hg; however, an optimal cut point for this population has not been established. Based on the available evidence, it appears that blood pressure targets will probably have to be lower than <140/90mmHg, and that values approaching 130/80mmHg should be recommended. Initial treatment of hypertension in diabetes should include drug classes demonstrated to reduce cardiovascular events; i.e., angiotensin converting-enzyme inhibitors, angiotensin receptor blockers, diuretics, or dihydropyridine calcium channel blockers. The start of therapy must be individualized in accordance with the patient's baseline characteristics, and factors such as associated comorbidities, race, and age, inter alia.

Left Ventricular Mechanical Reverse Remodelling Not Followed by Electrical Reverse Remodelling: A Case Report

Cardiology ◽  
2017 ◽  
Vol 138 (2) ◽  
pp. 80-86
Author(s):  
Sandra Amorim ◽  
Raquel Garcia ◽  
Teresa Pinho ◽  
João Rodrigues ◽  
Filipe Macedo ◽  
...  
Keyword(s):  
Left Ventricular ◽  
Pharmacological Therapy ◽  
Idiopathic Dilated Cardiomyopathy ◽  
Left Ventricular Ejection ◽  
Implantable Cardioverter Defibrillators ◽  
Icd Implantation ◽  
Cardiac Device ◽  
Myocardial Substrate ◽  
Reverse Remodelling ◽  
Life Threatening

Patients with severely depressed left ventricular ejection fractions (LVEFs) receive implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden death. However, in some patients, LVEFs may improve or even normalize over time, and these patients would no longer be qualified for ICD implantation based on the original criteria for which they have initially received an ICD. We report a patient with idiopathic dilated cardiomyopathy whose LVEF recovered to normal values after pharmacological therapy. Meanwhile, the patient had life-threatening ventricular fibrillation, aborted by the ICD. We reflect on the pathological features of left ventricular reverse remodelling and ventricular arrhythmogenesis, where the myocardial substrate appears to play an important role. Also, after LVEF improvement in a patient with a cardiac device, there is still a debate on whether we should perform a battery replacement.

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