engleski

Spironolactone in the treatment of chronic heart failure

During the last 50 years treatment of heart failure evolved from cardiorenal concept in 1940s, when digoxin and diuretics were used to perfuse kidneys, followed by hemodynamic concept in 1960-70s using vasodilatators to relieve ventricular wall stress, to neurohormonal concept with ACE inhibitors, beta blockers and other agents beeing now used to block neurohormonal activation. Today, neurohormonal system stands at the center of cardiovascular risk, especially in heart failure patients. Noradrenalin, angiotensin II, aldosterone, endothelin, vasopressin and some cytokines are neurohormones with the negative role in chronic heart failure. Among them, the role of aldosterone in progression of this common syndrome is frequently overlooked, and needs to be revaluated. Aldosterone production in adrenal gland is influenced by multiple regulators such as ACTH, angiotensin II, potassium, noradrenaline, endothelin, serotonin and nitric oxide. In heart failure patients, acting on specific receptors not only in renal collecting ducts, but also in brain, heart and vasculature, aldosterone exerts many deleterious effects on cardiovascular system, increasing morbidity and mortality. The levels of aldosterone correlate with the functional class, beeinh the highest in most severe patients (NYHA III-IV), and directly related to mortality. Aldosteron levels may fall initially in response to ACE inhibition or angiotensin II receptor blocade, but return to normal or above baseline after about 12 weeks ("escape"), because multiple homeostatic mechanisms exist to preserve mineralocorticoid activity. In heart failure spironolactone acts as a competitive antagonist of aldosterone receptor, blocking sodium and water retention, inhibiting potassium and magnesium excretion associated with arrhythmia occurrence, also preventing fibrosis and cardiovascular remodelling. In the RALES study, 25 mg of spironolactone added daily to standard treatment with ACE inhibitor, loop diuretic and digoxin in NYHA III-IV patients, reduced all-caused mortality by 30% (p<0.001), deaths from cardiac causes by 31% (p<0.001), hospitalizations for worsening heart failure by 35% (p<0.001), and improved symptoms (functional class) (p<0.001), with good tolerability when compared to placebo. According to current recommendations, mainly based on the RALES study results, spironolactone should be used in all patients with systolic LV dysfunction in NYHA III-IV functional class, in a dose of 25 mg daily, and in addition to standard treatment. It seems that multiple RAAS blockade is the best choice oh pharmacological treatment.

Chronic heart failure; Treatment; Spironolactone

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