Advances in cardiovascular treatment

Question 1

Give an example of an SGLT2 inhibitor and its MOA
What indication is it used in

Answer 1

Dapagliflozin

Type II
Standard treatment for patients with heart failure with reduced ejection fraction

Question 2

What are the cardiovascular benefits of SGLT2 inhibitors

Answer 2

Improved glycemic control
Reduction in body mass and blood pressure
Natriuresis and reduction in circulating volume

Question 3

What are natriuretic peptides?
Give examples
Where is it released?
What effect does it produce?

Answer 3

A family of peptides that promote natriuresis, diuresis and arterial relaxation (= increase in urinary sodium output)

Atrial Natriuretic Peptide (ANP)
Brain Natriuretic Peptide (BNP)
C- type Natriuretic Peptide (CNP)

Question 4

What is Neprilysin?

Question 5

What is Omapatrilat?
What are its effects?

Answer 5

A combined ACE inhibitor and neprilysin inhibitor

Reduces the pathological effects of excess RAAS system and potentiates the beneficial effects of increased natriuretic peptide effects

Question 6

What are the risk factors/negative effects of Omapatrilat?

Question 7

Natriuretic peptide agonists

Answer 7

Increase the beneficial effects of increasing natriuretic peptide signalling

It increases natriuresis and diuresis
Lowers arterial tone

*Stomach acids break down peptides so it can’t be administered orally
Only available in intravenous form

reduce breakdown or stimulate NP receptors

Question 7

Zilebesiran (ALN-AGT)

Answer 7

New therapy to reduce angiotensin levels
In phase 2 clinical trials

Question 7

Give an example of a combined angiotensin receptor blockade and neprilysin inhibitor (ARNI)?

Answer 7

Entresto
Angiotensin receptor blocker (Valsartan) + neprilysin inhibitor (Sacubitril)

Question 8

What are the effects of a combined angiotensin receptor blockade and neprilysin inhibitor (ARNI)?

Answer 8

Reduces pathological effects of excess RAAS system whilst potentiating the beneficial effects of increased natriuretic peptides.

Has a good safety profile

Question 9

Selective cardiac myosin activator

Answer 9

Omecamtiv mecarbil

increases myocardial systolic function by:

Activating myocardial ATPase and improving energy utilisation

enhances the myosin cross-bridge formation and duration

Improves cardiac muscle contractions

Question 10

Ivarbradine

Answer 10

I (f) channel inhibitor

inhibitors of the I (f) channel (funny current channel) in the sinus node

slows the heart rate

*for severe heart failure and on other treatments (in trials)

Question 11

Firibastat

Answer 11

Brain amino peptidase A inhibitor
Phase 3 clinical trials

Question 13

Describe calcium channel blocker

Question 14

Describe angiotensin receptor antagonists

Question 15

How can peripheral resistance be reduced to reduce exertion of the heart?

Question 16

What are new cardiovascular drugs that reduce exertion on the heart for heart failure?

Question 17

What are SGLT2 inhibitors?

Answer 17

SGLT2 inhibitors prevent reabsorption of filtered glucose in the kidney, increasing urinary glucose excretion & reducing blood glucose levels

Inhibitos glucose reabsorption

*treatment for patients with heart failure and reduced ejection fraction.

Question 18

What are the cardiac benefits of SGLT2 inhibitors?

Answer 18

Improved glycemic control
Reduction in body mass
Natriuresis and reduction in circulating volume
Cardiac remodelling

Question 19

Explain left sided heart failure

Question 20

Explain right sided heart failure

Question 21

What are some of the side effects/risks of the current cardiovascular therapies?

Answer 21

ACEi/ARBs, beta-blockers and mineralocorticoid antagonists

Side effects/risks:

Hypotension
Impact on Kidneys/electrolytes

Question 22

What are some of the limitations of the current statins and fibrates?

Answer 22

Statins and fibrates are linked to mucscle aches, and can - in severe cases - cause muscle damage

Rhabdomyolysis

They are both rarely linked to liver damage

PCSK9 inhibitors are expensive

Question 23

Inclisarin

Answer 23

Small interfering RNA therapeutic

Targets PCSK9

Question 24

Mipomersen

Answer 24

Antisense oligonucleotide therapeutic

Mipomersen targets apoliporotein B-100

*not licensed in Europe or UK due to high incidence rates of severe liver adverse effects