The angiotensin receptor–neprilysin inhibitor LCZ696 was compared with the ACE inhibitor enalapril in patients with advanced heart failure. LCZ696 was superior to enalapril in all outcomes. ...Neprilysin inhibition may replace ACE inhibition for the treatment of heart failure.
Angiotensin-converting–enzyme (ACE) inhibitors have been the cornerstone of the treatment for heart failure and a reduced ejection fraction for nearly 25 years, since enalapril was shown to reduce the risk of death in two trials.
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Long-term treatment with enalapril decreased the relative risk of death by 16% among patients with mild-to-moderate symptoms.
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The effect of angiotensin-receptor blockers (ARBs) on mortality has been inconsistent,
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and thus, these drugs are recommended primarily for patients who have unacceptable side effects (primarily cough) while receiving ACE inhibitors. Subsequent studies showed that the use of beta-blockers and mineralocorticoid-receptor antagonists, when added to ACE . . .
Sodium–glucose cotransporter (SGLT)2 inhibitors have been demonstrated to reduce cardiovascular events, particularly heart failure, in cardiovascular outcome trials. Here, we review the proposed ...mechanistic underpinnings of this benefit. Specifically, we focus on the role of SGLT2 inhibitors in optimising ventricular loading conditions through their effect on diuresis and natriuresis, in addition to reducing afterload and improving vascular structure and function. Further insights into the role of SGLT2 inhibition in myocardial metabolism and substrate utilisation are outlined. Finally, we discuss two emerging themes: how SGLT2 inhibitors may regulate Na
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exchange at the level of the heart and kidney and how they may modulate adipokine production. The mechanistic discussion is placed in the context of completed and ongoing trials of SGLT2 inhibitors in the prevention and treatment of heart failure in individuals with and without diabetes.
In this trial, 2737 patients with heart failure and LV systolic dysfunction were given eplerenone or placebo in addition to recommended therapy. Eplerenone significantly reduced the risk of the ...primary outcome, a composite of death or hospitalization.
The activation of mineralocorticoid receptors by aldosterone and cortisol has deleterious effects in patients with cardiovascular disease.
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In the placebo-controlled Randomized Aldactone Evaluation Study (RALES),
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adding the mineralocorticoid-receptor antagonist spironolactone to recommended therapy in patients with systolic heart failure and moderate-to-severe symptoms (i.e., New York Heart Association NYHA functional class III or IV symptoms) decreased the rate of death from any cause and the risk of hospitalization for cardiovascular reasons. In the Eplerenone Post–Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS),
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the selective mineralocorticoid-receptor antagonist eplerenone, added to recommended medical therapy, reduced the rates of death from any . . .
Data were analyzed from 40,195 patients with heart failure with reduced ejection fraction enrolled in 12 clinical trials in the 1995–2014 period. Sudden-death rates declined substantially over time, ...a finding consistent with a cumulative effect of evidence-based medical therapy.
The angiotensin-receptor-neprilysin inhibitor (ARNI) LCZ696 reduced cardiovascular deaths and all-cause mortality compared with enalapril in patients with chronic heart failure in the prospective ...comparison of ARNI with an Angiotensin-Converting Enzyme Inhibitor to Determine Impact on Global Mortality and Morbidity in Heart Failure (PARADIGM-HF) trial. To more completely understand the components of this mortality benefit, we examined the effect of LCZ696 on mode of death.
PARADIGM-HF was a prospective, double-blind, randomized trial in 8399 patients with chronic heart failure, New York Heart Association Class II-IV symptoms, and left ventricular ejection fraction ≤40% receiving guideline-recommended medical therapy and followed for a median of 27 months. Mode of death was adjudicated by a blinded clinical endpoints committee. The majority of deaths were cardiovascular (80.9%), and the risk of cardiovascular death was significantly reduced by treatment with LCZ (hazard ratio, HR 0.80, 95% CI 0.72-0.89, P < 0.001). Among cardiovascular deaths, both sudden cardiac death (HR 0.80, 95% CI 0.68-0.94, P = 0.008) and death due to worsening heart failure (HR 0.79, 95% CI 0.64-0.98, P = 0.034) were reduced by treatment with LCZ696 compared with enalapril. Deaths attributed to other cardiovascular causes, including myocardial infarction and stroke, were infrequent and distributed evenly between treatment groups, as were non-cardiovascular deaths.
LCZ696 was superior to enalapril in reducing both sudden cardiac deaths and deaths from worsening heart failure, which accounted for the majority of cardiovascular deaths.
https://clinicaltrials.gov/, NCT01035255.
The effects of renin–angiotensin–aldosterone system blockers on angiotensin-converting enzyme 2 levels and activity in humans are uncertain. The authors hypothesize that ACE2 may be beneficial rather ...than harmful during lung injury and suggest that RAAS-inhibitor withdrawal may be harmful in some high-risk patients with known or suspected Covid-19.
Dalcetrapib, an inhibitor of cholesteryl ester transfer protein, raises HDL cholesterol levels. In this clinical trial involving patients with an acute coronary syndrome, dalcetrapib had no ...beneficial effect on clinical outcomes, despite raising HDL cholesterol levels.
High-density lipoproteins (HDLs) participate in the process of cellular cholesterol efflux and may have additional protective effects against atherothrombosis.
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An inverse association between levels of HDL cholesterol and incident events of coronary heart disease has been shown in observational studies
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and persists in most post hoc analyses and meta-analyses of trials of statin therapy for patients with cardiovascular risk factors, chronic cardiovascular disease, or recent acute coronary syndrome.
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However, it remains uncertain whether pharmacologic intervention that raises HDL cholesterol levels results in decreased cardiovascular risk.
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Moreover, changes in HDL cholesterol levels may not reflect changes in the . . .
Dapagliflozin in Patients with Chronic Kidney Disease Heerspink, Hiddo J.L; Stefánsson, Bergur V; Correa-Rotter, Ricardo ...
The New England journal of medicine,
10/2020, Letnik:
383, Številka:
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Journal Article
Recenzirano
Odprti dostop
In this trial, patients with CKD (with or without type 2 diabetes) were randomly assigned to receive dapagliflozin or placebo. The primary composite outcome — a sustained decline in the estimated GFR ...of at least 50%, end-stage kidney disease, or death from renal or cardiovascular causes — was less frequent with dapagliflozin.
In this randomized study, the addition of lixisenatide, a glucagon-like peptide 1–receptor agonist, to usual care in patients with type 2 diabetes and a recent cardiovascular event did not alter the ...rate of subsequent major cardiovascular or other serious adverse events.
Randomized trials involving patients with new or established type 2 diabetes have shown that improved glucose control reduces the risk of microvascular complications,
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with modest cardiovascular benefits suggested by meta-analyses and extended follow-up of clinical trials.
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However, various studies indicate that, despite being effective in lowering the glucose and glycated hemoglobin levels, some hypoglycemic medications may increase, rather than reduce, the risk of cardiovascular events.
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These unexpected findings prompted the reexamination of the regulatory approval processes for new antidiabetic therapies, which had been based primarily on the surrogate measure of glucose lowering with limited clinical-outcomes data. Since . . .
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