cardiovascular-agents and candesartan

Our aim was to describe the incidence and predictors of stroke in patients who have heart failure without atrial fibrillation (AF).. We pooled 2 contemporary heart failure trials, the Controlled Rosuvastatin in Multinational Trial Heart Failure (CORONA) and the Gruppo Italiano per lo Studio della Sopravvivenza nell'Insufficienza cardiaca-Heart Failure trial (GISSI-HF). Of the 9585 total patients, 6054 did not have AF. Stroke occurred in 165 patients (4.7%) with AF and in 206 patients (3.4%) without AF (rates 16.8/1000 patient-years and 11.1/1000 patient-years, respectively). Using Cox proportional-hazards models, we identified the following independent predictors of stroke in patients without AF (ranked by χ(2) value): age (hazard ratio, 1.34; 95% confidence interval, 1.18-1.63 per 10 years), New York Heart Association class (1.60, 1.21-2.12 class III/IV versus II), diabetes mellitus treated with insulin (1.87, 1.22-2.88), body mass index (0.74, 0.60-0.91 per 5 kg/m(2) up to 30), and previous stroke (1.81, 1.19-2.74). N-terminal pro B-type natriuretic peptide (available in 2632 patients) was also an independent predictor of stroke (hazard ratio, 1.31; 1.11-1.57 per log unit) when added to this model. With the use of a risk score formulated from these predictors, we found that patients in the upper third of risk had a rate of stroke that approximated the risk in patients with AF.. A small number of demographic and clinical variables identified a subset of patients who have heart failure without AF at a high risk of stroke.

Topics: Adult; Aged; Aged, 80 and over; Atrial Fibrillation; Benzimidazoles; Biomarkers; Biphenyl Compounds; Cardiovascular Agents; Diabetes Mellitus, Type 1; Fatty Acids, Omega-3; Female; Fluorobenzenes; Follow-Up Studies; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Kaplan-Meier Estimate; Male; Middle Aged; Natriuretic Peptide, Brain; Peptide Fragments; Proportional Hazards Models; Pyrimidines; Randomized Controlled Trials as Topic; Risk Factors; Rosuvastatin Calcium; Stroke; Stroke Volume; Sulfonamides; Tetrazoles

Heart failure with preserved ejection fraction (HF-PEF) is the clinical syndrome of heart failure associated with normal or near-normal systolic function. Because inhibition of the adrenergic and renin-angiotensin-aldosterone systems has been so effective in the treatment of systolic heart failure, these same therapies have been the subject of recent clinical trials of HF-PEF. In this review, we examine the current evidence about treatment of HF-PEF, with particular emphasis on reviewing the literature for large-scale randomized clinical studies. The lack of significant benefit with neurohormonal antagonism in HF-PEF suggests that this condition might not involve neurohormonal activation as a critical pathophysiologic mechanism. Perhaps heart failure as we traditionally think of it is the wrong paradigm to pursue as we try to understand this condition of volume overload known as HF-PEF.

Topics: Adrenergic beta-Antagonists; Angiotensin II Type 1 Receptor Blockers; Angiotensin-Converting Enzyme Inhibitors; Benzimidazoles; Biphenyl Compounds; Calcium Channel Blockers; Cardiovascular Agents; Digitalis Glycosides; Exercise; Exercise Tolerance; Heart Failure; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertrophy, Left Ventricular; Irbesartan; Mineralocorticoid Receptor Antagonists; Randomized Controlled Trials as Topic; Renin-Angiotensin System; Stroke Volume; Tetrazoles; Ventricular Dysfunction, Left; Verapamil

The publication of trials of angiotensin receptor blockers (ARBs) in recent years has led to the need to update the European Society of Cardiology guidelines for the management of chronic heart failure. Of primary importance among these studies were the three trials of the CHARM program comparing candesartan and placebo in patients with chronic heart failure. In CHARM-Alternative, candesartan significantly reduced the risk of cardiovascular death or hospitalization for heart failure in patients who could not tolerate angiotensin-converting enzyme (ACE) inhibitors. This risk was also significantly lowered by candesartan in CHARM-Added, which included patients who were already on ACE inhibitor therapy. At borderline significance, the risk of cardiovascular death or hospitalization for heart failure was reduced by candesartan in CHARM-Preserved, which included patients who presented with preserved systolic function and left ventricular ejection fraction. Candesartan also significantly reduced the risk of new-onset diabetes and of atrial fibrillation in the CHARM-Overall study.

Topics: Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Cardiovascular Agents; Chronic Disease; Drug Therapy, Combination; Heart Failure; Hospitalization; Humans; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Tetrazoles; Treatment Outcome; Ventricular Function, Left

Excessive vascular smooth muscle cell (VSMC) proliferation contributes to vascular remodeling and stroke during hypertension. Blockade of Angiotensin (AngII) type 1 receptor (AT

Topics: Benzimidazoles; Biphenyl Compounds; Cardiovascular Agents; Cell Proliferation; Cells, Cultured; Down-Regulation; Gene Expression Regulation, Developmental; Humans; MicroRNAs; Muscle, Smooth, Vascular; STAT3 Transcription Factor; Tetrazoles

We determined effects of the vasopeptidase inhibitor (VPI) omapatrilat and angiotensin II type 1 receptor (AT(1)R) blocker (ARB) candesartan in rats during healing between day-2 and day-21 after reperfused myocardial infarction (RMI) on left ventricular (LV) remodeling and function, and regional matrix metalloproteinase (MMP)-9, tissue inhibitor of MMP (TIMP)-3, inducible-nitric-oxide-synthase (iNOS), oxidant-generating myeloperoxidase (MPO), and cytokines tumor-necrosis-factor (TNF)-alpha, interleukin (IL)-6 and IL-10, and transforming-growth-factor (TGF)-beta(1), and collagens. Compared to RMI-placebo, both agents reversed adverse LV remodeling and systolic and diastolic dysfunction, improved collagen remodeling, and normalized MMP-9 (activity, protein, and mRNA), TIMP-3 (protein and mRNA), and iNOS, MPO, TNF-alpha, IL-6, and TGF-beta(1) proteins, and improved MMP-9/TIMP-3 balance and IL-10 levels in previously ischemic zones. The results suggest that modulation of matrix proteases, oxidants, cytokines, and NOSs with omapatrilat and candesartan contribute to reversal of adverse collagen and LV remodeling and attenuation of LV dysfunction during healing after RMI.

Topics: Angiotensin II Type 1 Receptor Blockers; Animals; Benzimidazoles; Biphenyl Compounds; Cardiovascular Agents; Cytokines; Extracellular Matrix; Humans; Isoenzymes; Matrix Metalloproteinase 2; Matrix Metalloproteinase 9; Myocardial Reperfusion; Myocardium; Nitric Oxide Synthase; Peroxidase; Protease Inhibitors; Pyridines; Random Allocation; Rats; Tetrazoles; Thiazepines; Tissue Inhibitor of Metalloproteinase-1; Tissue Inhibitor of Metalloproteinase-3; Ventricular Remodeling

Topics: Angiotensin Receptor Antagonists; Benzimidazoles; Biphenyl Compounds; Cardiovascular Agents; Heart Failure; Hospitalization; Humans; Tetrazoles