Spironolactone should be initiated at a dose of 12.5 to 25 mg daily, or occasionally on alternate days. Eplerenone was used after MI in one study at doses of 25 mg per day, increasing to 50 mg daily. Potassium supplementation is generally stopped after the initiation of aldosterone antagonists, and patients should be counseled to avoid high potassium–containing foods. However, patients who have required large amounts of potassium supplementation may need to continue receiving supplementation, albeit at a lower dose, particularly when previous episodes of hypokalemia have been associated with ventricular arrhythmias.
Patients should be cautioned to avoid the addition of nonsteroidal anti-inflammatory agents and cyclo-oxygenase-2 inhibitors, which can lead to worsening renal function and hyperkalemia.
Potassium levels and renal function should be rechecked within 3 days and again at 1 week after initiation of an aldosterone antagonist. Subsequent monitoring should be dictated by the general clinical stability of renal function and fluid status but should occur at least monthly for the first 3 months and every 3 months thereafter. The addition or an increase in dosage of ACEIs or ARBs should trigger a new cycle of monitoring.
In view of the potential risk for hyperkalemia, the routine triple combination of ACEIs, ARBs, and an aldosterone antagonist should be avoided. The development of potassium levels in excess of 5.5 mEq per liter should generally trigger discontinuation or dose reduction of the aldosterone antagonist, unless patients have been receiving potassium supplementation, which should then be stopped. The drug should also be stopped if the patient develops painful gynecomastia.
Finally, patients should be instructed specifically to stop the aldosterone antagonist during an episode of diarrhea or while loop diuretic therapy is interrupted.
BETA-ADRENERGIC RECEPTOR BLOCKERS
Beta-blockers act principally to inhibit the adverse effects of the sympathetic nervous system in patients with HF. Indeed, although cardiac adrenergic drive initially supports the performance of the failing heart, long-term activation of the sympathetic nervous system exerts deleterious effects that can be antagonized by the use of beta-blockers.
Sympathetic activation can increase ventricular volumes and pressure by causing peripheral vasoconstriction and by impairing sodium excretion by the kidneys.
Norepinephrine can also induce cardiac hypertrophy, restricting, at the same time, the ability of the coronary arteries to supply blood to the thickened ventricular wall, leading to a latent status of myocardial ischemia70.
70 Simons M, Downing SE. Coronary vasoconstriction and catecholamine cardiomyopathy. Am Heart J 1985;109:297-304.