W4 - lipid update/effect on CVS

Question 1

A 76 yr old patient with previous MI and BP 140/80 on atenolol. Would you lower his BP further? If yes, what could you use?

Answer 1

Yes - to 120/80 using:

• thiazides as FIRST-LINE
• loop diuretics for ADVANCED CKD
• b-adrenergic blocker for CAD

Question 2

How does Evolocumab work?

Answer 2

PCSK9 monoclonal antibody

PCSK9 = proprotein convertase subtilisin kexin 9 = loss of function mutations lead to HIGHER levels of LDL receptor = lower [LDL cholesterol] = protection from CHD

Question 3

How are PCSK9 monoclonal antibodies used in practice?

Answer 3

evolocumab reserved for high risk patients:

• statin intolerant
• uncontrolled lipids (especially familial hyperlipidaemia patients)
• high net value patients (aka rich)

Question 4

Effect of evolocumab on mortality?

Answer 4

does NOT reduce death rate

Question 5

T2DM - How long of good glucose control and at which point of disease is it needed to prevent complications? Why?

Answer 5

For 15 years after NEWLY diagnosed T2DM

• Once arteries become atheromatic, intense glucose lowering will precipitate an adverse outcome = increase mortality

Question 6

How long of good glucose control and at which point of disease is it needed to prevent complications? Why?

Answer 6

For 15 years after NEWLY diagnosed T2DM

Question 7

Define legacy effect

Answer 7

tight glucose control AT THE BEGINNING is imp as the benefits (i.e., reduced atheroma) are sustained after the cessation of randomised intervention = legacy effect.

Benefits are sustained for up to 10 years after cessation of intervention

Question 8

What was the outcome of the ACCORD study?

Answer 8

Older people who had poor control for long time (atheromatic arteries), suddenly massively tightened control (A1C = 6%), and caused increased MORTALITY

Question 9

What was the outcome of the ADVANCE study?

Answer 9

Set a higher A1C threshold than ACCORD study (6.5 vs 6.0), and REDUCED mortality

Question 10

MOA of SGLT2 inhibitors?

Answer 10

SGLT2 inhibitor will block SGLT2 receptor in proximal tubule = block glucose reabsorption = increased glucose excretion

Question 11

SGLT2 inhibitor drug name

Answer 11

Empagliflozin

Question 12

What was the outcome of the EMPA-REG study?

Answer 12

Empagliflozin improves eGFR and causes reduction in A1c, SBP, DBP, weight, waist circumference, and mortality in patients with T2DM + CVD

Question 13

GLP-1 analogue names, caveats

Answer 13

Exanatide
Liraglutide (Saxenda)
Semaglutide

caveats: injection, expensive

Question 14

Side effects of Empagliflozin

Answer 14

Dehydration, UTI

Question 15

Name of DDP-4 inhibitor drug

Answer 15

sitagliptin