Heart failure spironolactone

Spironolactone. Plasma aldosterone is elevated in heart failure. Spironolactone acts as a diuretic by competitively blocking the aldosterone-receptor, but in addition it has a powerful effect on outcome in cardiac failure (see below). 

The addition of aldosterone antagonists can rednce morbidity and mortality in systolic heart failure. Spironolactone has been studied in severe heart failure and has shown benefit in addition to diuretic and ACE inhibitor therapy. Eplerenone, the newest aldosterone antagonist, has been smdied in patients with symptomatic systolic heart failure within 3 to 14 days after an acute myocardial infarction in addition to a standard three-drug regimen. Collectively, both these agents should be considered in the specific heart failure population smdied but only in addition to diuretics, ACE/ARBs, and /8-blockers. 

Answer E. In approaching the answer to this question, try to sort out the incorrect statements. Spironolactone does not cause hypokalemia, but hyperkalemia. Although loop diuretics may cause hyperuricemia, there is no connection between elevations of uric add and fainting episodes. When used with ACEIs in the treatment of heart failure, spironolactone is reported to increase survival, but there is no evidence of similar efficacy in patients with HTN. Obviously, statement B is erroneous (never choose never ). Although postural hypotension from the combination of antihypertensive drugs is most likely responsible for the fainting episode in this patient, there could also be alternative explanations ... 

ACE inhibitors do not completely block aldosterone synthesis. Since this steroid hormone is a potent inducer of fibrosis in the heart, specific antagonists, such as spironolactone and eplerenone, have recently been very successfully used in clinical trials in addition to ACE inhibitors to treat congestive heart failure [5]. Formerly, these drugs have only been applied as potassium-saving diuretics in oedematous diseases, hypertension, and hypokalemia as well as in primary hyperaldosteronism. Possible side effects of aldosterone antagonists include hyperkalemia and, in case of spironolactone, which is less specific for the mineralocorticoid receptor than eplerenone, also antiandrogenic and progestational actions. 

If the patient has marked limitation of physical activity or is unable to carry out physical activity without discomfort and symptoms of heart failure or angina are present, consider administering spironolactone... 

To reduce mortality, administration of an aldosterone antagonist, either eplerenone or spironolactone, should be considered within the first 2 weeks following MI in all patients who are already receiving an ACE inhibitor (or ARB) and have an EF of equal to or less than 40% and either heart failure symptoms or diagnosis of diabetes mellitus.3 Aldosterone plays an important role in heart failure and in MI because it promotes vascular and myocardial fibrosis, endothelial dysfunction, hypertension, left ventricular hypertrophy, sodium retention, potassium and magnesium loss, and arrhythmias. Aldosterone antagonists have been shown in experimental and human studies to attenuate these adverse effects.70 Spironolactone decreases all-cause mortality in patients with stable, severe heart failure.71... 

Either eplerenone or spironolactone should be considered within the first 2 weeks after MI to reduce mortality in all patients already receiving an ACE inhibitor who have LVEF <40% and either heart failure symptoms or a diagnosis of diabetes mellitus. The drugs are continued indefinitely. Example oral doses include the following ... 

FIGURE 8-2. General treatment algorithm for acute decompensated heart failure (ADHF) based on clinical presentation. IV vasodilators that may be used include nitroglycerin, nesiritide, or nitroprusside. Metolazone or spironolactone may be added if the patient fails to respond to loop diuretics and a second diuretic is required. IV inotropes that may be used include dobutamine or milrinone. (D/C, discontinue HF, heart failure SBP, systolic blood pressure.) (Reprinted and adapted from J Cardiac Fail, Vol 12, pages el-el 22, copyright 2006, with permission from Elsevier.)... 

Agostoni P, Magini A, Andreini D, Contini M, Apos-tolo A, Bussotti M et al. Spironolactone improves lung diffusion in chronic heart failure. Eur Heart J 2005 269(2) 159-64. 

Pitt B et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. 

Triamterene can be used in the treatment of congestive heart failure, cirrhosis, and the edema caused by secondary hyperaldosteronism. It is frequently used in combination with other diuretics except spironolactone. Amiloride, but not triamterene, possesses antihypertensive effects that can add to those of the thiazides. 

Spironolactone Block aldosterone receptor in renal collecting tubule Increase Na and decrease excretion poorly understood reduction in heart failure mortality Aldosteronism, heart failure, hypertension ... 

Diuretics are the mainstay of heart failure management and are discussed in detail in Chapter 15. They have no direct effect on cardiac contractility their major mechanism of action in heart failure is to reduce venous pressure and ventricular preload. This results in reduction of salt and water retention and edema and its symptoms. The reduction of cardiac size, which leads to improved pump efficiency, is of major importance in systolic failure. Spironolactone and eplerenone, the aldosterone antagonist diuretics (see Chapter 15), have the additional benefit of decreasing morbidity and mortality in patients with severe heart failure who are also receiving ACE inhibitors and other standard therapy. One possible mechanism for this benefit lies in accumulating evidence that aldosterone may also cause myocardial and vascular fibrosis and baroreceptor dysfunction in addition to its renal effects. 

Spironolactone Block cytoplasmic aldosterone receptors in collecting tubules of nephron possible membrane effect Increased salt and water excretion reduces remodeling reduces mortality Chronic heart failure aldosteronism (cirrhosis, adrenal tumor) hypertension Oral duration 24-72 h (slow onset and offset) Toxicity Hyperkalemia, antiandrogen actions... 

Spironolactone as a diuretic is discussed in Chapter 15. The drug has benefits in heart failure greater than those predicted from its diuretic effects alone (see Chapter 13). Adverse effects reported for spironolactone include hyperkalemia, cardiac arrhythmia, menstrual abnormalities, gynecomastia, sedation, headache, gastrointestinal disturbances, and skin rashes. 

It has also been suggested that certain diuretics such as spironolactone (Aldactone) might be especially helpful in heart failure.14,42 Spironolactone blocks aldosterone receptors in the kidneys and other tissues, thereby producing a diuretic effect as well as preventing adverse cardiovascular changes associated with excess aldosterone production. Future studies will help clarify whether spironolactone should be used preferentially in heart failure because of its ability to reduce fluid volume and protect against aldosterone-induced damage.53... 

Sodium removal is the next important step—by dietary salt restriction or a diuretic—especially if edema is present. In mild failure, it is reasonable to start with a thiazide diuretic, switching to more powerful agents as required. Sodium loss causes secondary loss of potassium, which is particularly hazardous if the patient is to be given digitalis. Hypokalemia can be treated with potassium supplementation or through the addition of a potassium-sparing diuretic such as spironolactone. As noted above, spironolactone should probably be considered in all patients with moderate or severe heart failure since it appears to reduce both morbidity and mortality. 

Clinical benefits and effects on mortality and hospitalization Whether used alone or in combination, hydralazine and isosorbide dinitrate decrease the preload and afterload, decrease mitral regurgitation, improve cardiac output, increase exercise capacity, modestly increase LVEF and prolong survival in patients with HF (63,64). V-Heart Failure Trial (HeFT) II (64) showed that enalapril had a major benefit on survival when compared with the combination of hydralazine-isosorbide dinitrate with enalapril in patients with predominantly NYHA class ll-lll. The African Americans in Heart Failure Trial (A-HeFT) (65) showed a beneficial effect of adding vasodilator therapy to African-American patients already treated with ACE inhibitors, (3 blockers, and spironolactone. There are no results with the same strategy in other patient groups. 

Struthers AD, Why does spironolactone improve mortality over and above an ACE inhibitor in chronic heart failure Br J Clin Pharmacol I 999 47 479-482. 

Zannad F Alla F Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may contribute to survival benefit of spironolactone therapy in patients with congestive heart failure insights from the randomized aldac-tone evaluation study (RALES). Rales Investigators. Circulation 2000 102 2700-2706. 

Pitt B, Zannad F Remme WJ, et al. The effect of spironolactone on morbidity and mortality in patients with severe heart failure. Randomized Aldactone Evaluation Study Investigators. N EnglJ Med 1999 341 709-717. 

Thiazide diuretics are ineffective once the GFR becomes less than 25 mL/min, and loop diuretics are often used at high doses (e.g. furosemide 500 mg to 1 g daily) to gain an effect. Metolazone is effective when combined with a loop diuretic. Potassium-sparing diuretics such as amiloride are not recommended. Spironolactone is not generally used, but is beneficial in low dose for the treatment of heart failure even in patients on dialysis. Beta-blockers and calcium channel blockers are generally well tolerated. Any ankle swelling with calcium channel blockers must not be confused with fluid overload. 

PROGESTOGENS 1. ANALGESICS -NSAIDs 2. ANTI HYPERTENSIVES AND HEART FAILURE DRUGS - ACE inhibitors, angiotensin II receptor antagonists 3. DIURETICS — potassium-sparing t risk of hyperkalaemia Drospirenone (component of the Yasmin brand of combined contraceptive pill) is a progestogen derived from spironolactone that can cause potassium retention Monitor serum potassium weekly until stable and then every 6 months... 

The RALES trial randomised 1663 patients with stable heart failure to either placebo or spironolactone (New England Journal of Medicine 1999 341 709). All patients were maintained on their optimised therapy that included ACE inhibitors. After 2 years of follow-up the trial was terminated prematurely due to a 30% reduction of mortality in the spironolactone treated patients both progressive pump failure and sudden death were significanly reduced. Gynaecomastia or breast discomfort occurred in 10% of treated patients (1% in controls), but significant h) erkalemia occurred in surprisingly few patients. RALES was not adequately powered to decide whether the action of spironolactone is additive to that of a p-blocker. 

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