10 - Heart Failure (Beta Blockers, MRAs, SGLT-2 Inhibitors, Diuretics, ISDN/Hydralazine)

What is the MOA of beta blockers in heart failure?

decreased beta-receptor mediated effects of catecholamines to lower SNS compensatory mechanisms:

• decreased HR, FOC

• initially decreases CO, but can improve over time

What is the clinical outcome of beta blockers?

reduced mortality

What beta blockers are proven to reduce mortality?

1. metoprolol succinate

2. carvedilol

3. bisoprolol

What are the adverse effects of beta blockers?

• worsening heart failure - start low, go slow for tolerance to decreased CO; titrate doses after 2 weeks

• bradycardia, bronchospasm, hypotension, hypoglycemia

What are the available mineralocorticoid receptor antagonists (MRA)?

spironolactone, eplerenone, finerenone

What is the MOA of MRAs?

inhibits all effects of aldosterone at the MR, with effects on cardiac remodeling:

• decreased preload, increased SV and CO

• decreased SNS activation

T/F: benefits of MRA are from diuretic effects

false; doses used in HF are inadequate for diuresis

What is the clinical outcome of MRAs?

decreased mortality

What are the ADE of MRAs?

• hyperkalemia

• gynecomastia

What must be monitored when on a MRA?

K+, SCr at baseline and within 1 week of initiation/dose change

What are the available SGLT2 inhibitors?

empagliflozin, dapagliflozin, canagliflozin, sotagliflozin

What is the MOA of SGLT2 inhibitors?

block reabsorption of glucose and Na+ in the proximal tubule; glucose in the more distal parts of the renal tubule acts as osmotic diuretic, reducing Na+/water reabsorption

What is the effect of SGLT2 inhibitors on compensatory mechanisms?

1. causes natriuresis/diuresis, decreasing preload

2. decreases afterload

also can reduce inflammation, cardiac remodeling, etc.

What is the clinical outcome of SGLT2 inhibitors?

reduce hospitalizations

T/F: SGLT2 inhibitors show benefits in patients with & without diabetes

true

What are the ADE of SGLT2 inhibitors?

• hypotension

• AKI

• hypoglycemia

• with diabetes → UTI, bone fracture, DKA, etc.

What should be monitored when on SGLT2 inhibitors?

glucose, BP, SCr, volume status

Which diuretic class is beneficial in heart failure?

loop diuretics

What are the clinical outcomes of diuretics?

reduced hospitalizations by relieving congestive symptoms

What is the MOA of isosorbide dinitrate (ISDN)/hydralazine?

• ISDN: prodrug producing NO and dilating large venous capitance vessels

• Hydralazine: direct arterial vasodilator

What is the effect of ISDN/hydralazine on compensatory mechanisms?

decreased preload and afterload → increased SV and CO

What is the clinical outcome of ISDN/hydralazine?

reduces mortality

• less than ARNI, ACEI, or ARB

• considered an alternative if intolerant to these

What are the ADE of ISDN/hydralazine?

hypotension, headache, increased HR, fluid retention

What are the concerns associated with ISDN/hydralazine use?

• nitrate tolerance is insignificant

• contraindicated with PDE-5 inhibitors