Other Positive Inotropic Drugs Used in Heart Failure

OTHER POSITIVE INOTROPIC DRUGS USED IN HEART FAILURE

Istaroxime is an investigational steroid derivative that increasescontractility by inhibiting Na⁺/K⁺-ATPase (like cardiac glycosides) but in addition facilitates sequestration of Ca²⁺ by the SR. The latter action may render the drug less arrhythmogenic than digoxin. Istaroxime is in phase 2 clinical trials.

Drugs that inhibit phosphodiesterases, the family of enzymes that inactivate cAMP and cGMP, have long been used in therapy of heart failure. Although they have positive inotropic effects, most of their benefits appear to derive from vasodilation, as dis-cussed below. The bipyridines inamrinone and milrinone are the most successful of these agents found to date, but their usefulness is limited. Levosimendan, a drug that sensitizes the troponin system to calcium, also appears to inhibit phosphodiesterase and to cause some vasodilation in addition to its inotropic effects. Some clinical trials suggest that this drug may be useful in patients with heart failure, and the drug has been approved in some countries (not the USA). A group of β-adrenoceptor stimulants has also been used as digitalis substitutes, but they may increase mortality .