Heart Failure Drugs

Digitalis

is the name of the genus of plants that provide most of the medically useful cardiac glycosides

Digoxin

is not extensively metabolized in humans; almost

two thirds is excreted unchanged by the kidneys.

36-40 hours

Digoxin half life

Na+/K+-ATPase

At the molecular level, all therapeutically useful cardiac glycosides inhibit

Cardiac glycosides

It increase contraction of the cardiac sarcomere by increasing the free calcium concentration in the vicinity of the contractile proteins during systole

Milrinone

is a bipyridine compound that inhibits phosphodiesterase isozyme 3 (PDE-3)

Milrinone

It has an elimination halflife of 3–6 hours, with 10–40% being excreted in the urine

The bipyridines

increase myocardial contractility by increasing inward calcium flux in the heart during the action potential;

they may also alter the intracellular movements of calcium by influencing the SR

Dobutamine

is the selective β1 agonist that has been most widely

used in patients with acute decompensated heart failure.

Dobutamine

This parenteral drug can produce an increase in cardiac output together

with a decrease in ventricular filling pressure.

Istaroxime

is an investigational steroid derivative that increases contractility by inhibiting Na+/K+-ATPase (like cardiac glycosides)

but in addition appears to facilitate sequestration of Ca2+ by the SR.

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.

Omecamtiv mecarbil

is an investigational parenteral agent

that activates cardiac myosin and prolongs systole without increasing oxygen consumption of the heart.

furosemide

Diuretic that is first choice in heart failure

Diuretics

their major mechanism of hemodynamic action in heart

failure is to reduce venous pressure and ventricular preload

Spironolactone and eplerenone

steroidal antagonist diuretics that 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

Finerenone

is a nonsteroidal mineralocorticoid

antagonist that may be less likely to induce hyperkalemia.

ACE Inhibitors

These versatile drugs reduce peripheral resistance and thereby reduce afterloadthey also reduce

salt and water retention (by reducing aldosterone secretion) and in that way reduce preload.

Losartan

appear to have similar beneficial effects like ACE Inhibitors. In combination with sacubitril, valsartan is now approved for HFrEF

Vasodilators

are effective in acute heart failure because they provide a reduction in preload (through venodilation), or reduction

in afterload (through arteriolar dilation), or both

hydralazine and isosorbide dinitrate

Long-term vasodilator that can also reduce damaging remodeling of the heart

Nesiritide

a synthetic form of the endogenous peptide brain

natriuretic peptide (BNP), is approved for use in acute (not chronic) cardiac failure.

Bisoprolol, carvedilol, metoprolol, and nebivolol

Beta blockers that showed a reduction in mortality in patients with stable severe heart failure

empagliflozin and dapagliflozin

SGLT2 inhibitors that increase renal sodium

excretion as well as glucose excretion

empagliflozin and dapagliflozin

They have complex effects in the heart, including inhibition of the sodiumhydrogen exchanger (NHE) and a reduction of glucose utilization

for ATP production.

Mavacamten

an inhibitor of myosin, is approved for use in obstructive hypertrophic cardiomyopathy

Furosemide

Loop diuretic: Decreases NaCl and KCl reabsorption in

thick ascending limb of the loop of Henle in the nephron

Furosemide and SGLT2 Inhibitors

Increased excretion of salt and water
• reduces cardiac preload and afterload

• reduces pulmonary and peripheral edema

The bipyridines

they have an important vasodilating effect. Inhibition of phosphodiesterase results in an increase in cAMP and the increase in contractility and vasodilation.

Systolic Failure (HFrEF)

• Affects ~50% of younger patients.

• Reduced contractility and ejection fraction.

Diastolic Failure (HFpEF)

• More common in older adults.

• Stiffened heart muscle reduces filling capacity.

• Ejection fraction is preserved, but stroke volume is reduced.

Treatment is therefore directed at two somewhat different goals:

(1) reducing symptoms and slowing progression as much as possible during relatively stable period

(2) managing acute episodes of decompensated failure.

Transthyretin amyloid cardiomyopathy (ATTR-CM) can be treated with

tafamidis

Levosimendan

is a drug that increases calcium sensitivity

omecamtiv mecarbil (CK-1827452)

alters the rate of transition of myosin from a low-actin-binding state to a strongly actin-bound, force-generating state and improves ejection fraction in the failing heart.

Digoxin

Inhibits Na⁺/K⁺-ATPase (sodium pump), increasing intracellular calcium.

neprilysin

which is responsible for the

degradation of BNP and atrial natriuretic peptide (ANP)

Sacubitril

is a pro drug that is metabolized to an active neprilysin inhibitor.

Liraglutide and semaglutide

GLP-1 agonists used in diabetes (see chapter 41) and obesity (see Chapter 16), have been shown to reduce deaths from cardiovascular causes as well as the rates of myocardial infarction, nonfatal stroke, and hospitalization for heart failure. They are approved for use in HFrEF.

Mavacamten

an inhibitor of myosin, is approved for use in

obstructive hypertrophic cardiomyopathy