Brief Lipid Update Flashcards
What is the statistical mortality benefit of adding a thiazide diuretic to outstanding BP medications, following an MI?
Worth it
2 in 100 will be prevented from a further MI in next 5 years
What is the statistical mortality benefit of adding a PCSK9 inhibitor to outstanding BP medications, following an MI?
Very effectively reduces LDL cholesterol
Decreases incidence of non-fatal MI/ Stroke
but does NOT reduce death
NNT HIGH
Give an example of a PCSK9 inhibitor medication, and how it works
Evolocumab
Regulates LDL-receptor expression to reduce cholesterol
What do PCSK9 gain and loss of function mutations result in?
Gain: reduce LDL-R on liver, high plasma LDL + increased susceptibility to CHD
Loss: increased LDL-R on liver, low plasma LDL + protection from CHD
Optimal management of CHD
Intensive lifestyle modification (exercise)
Aspirin
High dose statin: Atorvastatin 40-80mg OD
Optimal BP control: Thiazide diuretic
Assessment for T2DM: HbA1c
3 Options for statin-intolerant patients
Ezetemibe: reduced absorption
Plasma exchange
Evolocumab: PCSK9 monoclonal antibody
Which patients are PCSK9 inhibitors used in?
Statin intolerant- muscle aches
Uncontrolled lipids esp. Familial Hypercholesterolaemia
What did the UKPDS study show?
It takes 15 years for good glucose control to show a benefit
(For 9 years, there is little difference in risk of micro + macrovascular complications)
What happened after the UKPDS trial?
Glucose control became same as control group
Over next 10 years mortality remained lower in intensive tx group
= Legacy effect
Good control now prevents heart disease in future
What explanains the Legacy effect?
Tight control at start of disease keeps coronary arteries patent: sustained for a long time despite reverting to poor control later- benefits persist for at least 30 yrs after study.
Poor control allows coronary arteries to become furred up
What did the Advance study show?
Slightly less intense intervention into glucose control actually reduce death compared to aggressive intervention
What did the Accord study show?
Sudden aggressive blood glucose control in those with long term poor control leads to reduced complications (no of events) but increased mortality (hypoglycaemic events + arrhythmia)
What did the DCCT show?
Good control in T1DM improves outcome + legacy effect
4 benefits of SGLT2 inhibitors?
Reduce HbA1c
Reduce BP + cardiovascular disease (diuresis)
Prevent nephropathy (initial sharp reduction in GFR but recovers)
Waist circumference decreases
Very fast effect (4y)
What is the broad mechanism of action of SGLT2 inhibitors?
Reduce glucose re-uptake in kidneys
Cause osmotic diuresis + glycosuria
Name an SGLT-2 inhibitor
Empagliflozin
Give 3 examples of a GLP-1 analogues
Exenatide
Liraglutide
Semaglutide
What is the mechanism of action of the ‘gliptin’ drugs? Name an example
DPP4 inhibitors
Sitagliptin
Give 1 SE of SGLT2 inhibitors
Increased rate of UTI due to sugar in urine
Which SGLT2 inhibitor has divergent evidence of increasing amputation risk?
Canagliflozin
What is GLP-1?
Secreted from gut L cells
Signals pancreas to make insulin
Decreases appetite
Slows gastric emptying
Responsible for incretin effect
What is GLP-1 metabolised by?
DPP4
Thus inhibiting DPP4 using gliptins makes GLP-1 last longer
In which patients should Metformin be considered in?
All T2DM unless CI
Describe the stepwise management of T2DM
- Metformin
- Dual therapy
- Triple therapy
- Metformin + Sulphonylurea + GLP1 analogue
