Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease

Barr, Craig; Lang, Chim C.; Hanson, Jacqueline; Arnott, Michael; Kennedy, Norman; Struthers, Allan D.

doi:10.1016/s0002-9149(99)80353-1

Cited by 286 publications

(149 citation statements)

References 12 publications

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“…spironolactone may not reduce vascular events by the magnitude that its blood pressure-lowering alone would suggest. On the other hand, spironolactone might exert favourable anti-arrhythmic effects by way of its apparently beneficial effects on myocardial collagen and on QT interval length, as has also been seen in other populations [46,47]. Further work is required to explore the full clinical consequences of the issues raised by this study.…”

Section: Discussionmentioning

confidence: 75%

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

et al. 2008

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Aims/hypothesis Aldosterone antagonism improves endothelial function (and reduces deaths) in chronic heart failure. It is not known whether similar effects occur in other high-risk groups such as patients with diabetes and hypertension. We therefore assessed the full effects of aldosterone blockade in poorly controlled hypertensive patients with type 2 diabetes, focussing on blood pressure, endothelial function, glycaemic control and key hormones. Methods We performed a randomised, placebo-controlled, double-blind, crossover study on 50 patients with type 2 diabetes and treated but poorly controlled hypertension, comparing spironolactone versus placebo. Patients had their endothelial function assessed by standard forearm venous occlusion plethysmography. Results There was no significant improvement in endotheliumdependent vasodilatation in response to acetylcholine, despite highly significant reductions in systolic and diastolic blood pressure. However, spironolactone significantly worsened glycaemic control, plasma angiotensin II and cortisol. Conclusions/interpretation Spironolactone is highly effective in lowering blood pressure in patients with type 2 diabetes and poorly controlled hypertension on standard treatment, but does not improve vascular endothelial function in this group. We speculate that any tendency for the spironolactoneinduced lowering of blood pressure to improve endothelial function is offset by its tendency to worsen glycaemic control and increase the levels of angiotensin II and even possibly cortisol.Trials Registry no.: ISRCTN 76558770

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Section: Discussionmentioning

confidence: 75%

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

et al. 2008

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“…Aldosterone also causes direct vascular damage and baroreceptor dysfunction and prevents uptake of norepinephrine by the myocardium. 4,29,30 Recently, Pitt and coworkers 31 showed that blocking aldosterone with a low dose of spironolactone substantially reduced the risks of morbidity and mortality among patients with severe heart failure (RALES trial). Efficacy of an aldosterone blockade in their trial does not appear to be due entirely to prevention of sodium retention or potassium loss.…”

Section: Discussionmentioning

confidence: 99%

Aldosterone Production Is Activated in Failing Ventricle in Humans

et al. 2001

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Background-Recent reports have indicated that aldosterone is produced in extra-adrenal tissues in animals. The present study was designed to examine whether aldosterone is produced in human heart. Methods and Results-Plasma levels of aldosterone, BNP, and angiotensin-converting enzyme were measured in anterior interventricular vein (AIV), coronary sinus (CS), and aortic root (Ao), respectively, in 20 patients with left ventricular systolic dysfunction (LVSD), 25 patients with LV diastolic dysfunction (LVDD), and 23 control subjects. Aldosterone levels were significantly higher in AIV and CS than Ao in LVSD (98Ϯ10 versus 72Ϯ9 pg/mL, PϽ0.001, and 97Ϯ11 versus 72Ϯ9 pg/mL, PϽ0.001, respectively) and LVDD (87Ϯ10 versus 71Ϯ9 pg/mL, PϽ0.01, and 84Ϯ10 versus 71Ϯ9 pg/mL, PϽ0.01, respectively) groups, but no differences were observed in levels for these sites in the control group. Levels of ACE activity and BNP also were higher in AIV than Ao in both LV dysfunction groups. The difference in aldosterone levels between AIV and Ao and those in BNP and angiotensin-converting enzyme had a significant positive correlation with LVEDP and a significant negative correlation with LV ejection fraction in the LVSD group. Conclusions-Production

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“…Experimental data suggest that aldosterone influences the autonomic nervous system in animal models 34 and in man. 35 In particular, aldosterone antagonists increased myocardial norepinephrine uptake 36 and improved heart rate variability in patients with congestive heart failure. 37 Whether the cardiovascular effects of canrenone observed in this study possibly are due to an improved autonomic regulation remains to be established.…”

Section: Discussionmentioning

confidence: 99%

Cardiovascular effects of canrenone in patients with preascitic cirrhosis

et al. 2002

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In patients with cirrhosis and portal hypertension, standing induces a reduction in cardiac index (CI) and an increase in systemic vascular resistance index. Our previous studies indicate that this abnormal hemodynamic response to standing is due to an altered myocardial function, because cirrhotic patients are unable to compensate for the reduced preload with an increase in left ventricular (LV) ejection fraction (EF) and stroke volume. To evaluate whether the cardiac dysfunction in cirrhosis is influenced by canrenone, an aldosterone antagonist, 8 patients with preascitic, nonalcoholic cirrhosis, and portal hypertension underwent echocardiographic assessment of LV function and systemic hemodynamics and determinations of plasma volume, urinary sodium excretion, and plasma renin activity T he hemodynamic pattern of cirrhosis with portal hypertension, with high blood volume and cardiac output and low systemic vascular resistance (SVR), is thought to play a major role in the development of sodium retention and ascites. 1 Bernardi et al. [2][3][4] showed that this hemodynamic pattern occurs only in the supine position; standing is associated with a reduction in cardiac output and an increase in SVR, that is, a "normalization" of systemic hemodynamics. This response to standing is quite different from that of healthy subjects, who do not show any appreciable changes in either cardiac output or SVR. 2-4 However, "normalization" of systemic hemodynamics during standing is associated with activation of vasoconstricting and sodium retaining systems. 3,4 In patients with preascitic cirrhosis, sodium retention occurs only during standing, 3 whereas, in those with ascites, it occurs in either position but worsens during standing. 4 We recently evaluated cardiovascular function in healthy subjects and cirrhotic patients with ascites and hyperdynamic circulation. 5 When supine, patients had increased left ventricular ejection fraction (LVEF) and cardiac index (CI) and reduced LV end-systolic volume index (LVESVI) and SVR. On standing, LV end-diastolic volume index (LVEDVI) decreased in all subjects. Healthy subjects maintained CI and stroke volume index (SVI) by decreasing LVESVI. In contrast, cirrhotic patients experienced a fall in SVI and CI and a disproportionate increase in arterial elastance (Ea), despite marked

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Effects of adding spironolactone to an angiotensin-converting enzyme inhibitor in chronic congestive heart failure secondary to coronary artery disease

Cited by 286 publications

References 12 publications

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

Spironolactone for poorly controlled hypertension in type 2 diabetes: conflicting effects on blood pressure, endothelial function, glycaemic control and hormonal profiles

Aldosterone Production Is Activated in Failing Ventricle in Humans

Cardiovascular effects of canrenone in patients with preascitic cirrhosis

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