Meeran lipid update Flashcards
A 76 year old patient with a previous MI has a BP of 140/80 on atenolol.
LDL is 3.0mmol on atorvastatin 80mg
Is there evidence to lower his BP further?
To 140/80 (leave on atenolol)
To 120/80 (add a thiazide diuretic)
SPRINT trial - additional drug to furtehr lower BP or no further Rx - intensive group successful at keeping BP down. Sig lower primary outcome rate in those with lower blood pressure
Absolute risk is small - but half the death rate
Thiazides are very cheap
20% relative risk reduction and 2% absolute risk reducting
Using thiazides in 100n people with CAD –
Need to be aggressive with blood pressure control and lipid control
optimal medical therapy for hypertension
- Intensive lifestyle modificiation
- Aspirin
- Statin
- Optimise BP control
- Thiazides
- Assessment for probable T2 dm - check HbA1c
what is the role of PCSK9 monoclonal Ab
Protein regulates the LDL receptor - binds LDL receptor - controls rate of it being on the surface -
-> loss of function for this gene = have really low cholesterol.
If gain of function mutation = reduced LDL receptor in liver = high plasma LDL = increased susceptability to CHD
Ab (evolocumab) is to remove PCSK9 - really drops cholesterol to low levels
effectiveness of evolocumab
No differnece in death alone between evolocumab and placebo
Reduced MI but not death
Conclusions - benefit was achived - reduce LDL below current targets
To reduce 1 heart attack cost £600000 - very expensive
So use in statin intolerant, FH (works because reduces cholesterol)
problem with statin intolerance
Nocebo effect - people think there are Ses when you mention them
options available for statin intolerance
Ezetemibe
Plasma exchange where available
PCSK9 monoclonal Ab (evolocumab)
options available for statin intolerance
Ezetemibe
Plasma exchange where available
PCSK9 monoclonal Ab (evolocumab)
does good glucose control prevent complications
UK prospective diabetes study
- Conventional diet control vs intense control
- Follow for 10yrs
- Then looked on for furtehr 10 more years
- Intense control always better control than diet
- But up to 9 years no difference in outcomes - this is because risk at the start is low
- At 15 yrs - difference in endpoints
So good glucose control does prevent complications after 15yrs
Followed up another 10yrs later - difference in HbA1c disappeared - if don’t keep the tight control then the benefit is reduced. But mortality still better in the intense group - THE LEGACY EFFECT
If good control at the start when arteries are patent - benefits persist even when glucose becomes less well controlled.
summarise results from the ACCORD and ADVANCE study
- Patients with vascular disease
Accord - blood sugar went down with intensive therapy compared to controls.
Outcomes better in intense group, and deaths was worse.
Then stopped study because tight conbtrol late in life increased mortality - increased risk of hypoglycaemia and maybe arrhythmias - rosiglitazone
(accord reduced death)
summarise rsults from DCCT
young people,
insulin - everything got better with tight control
summarise SGLT2 inhibitors
Make you urine glucose - stop absorption
Wht loss
Lower HBA1c
Lowers BP and HR
Empagliflozin - reduced cardiac death - got better very early on within 6mos - good esp in people with HF
Diuretic so good benefits against HF
Only problem is UTIs more regularly because sugar in urine
In renal pts - osmotic preserver of glomeruli - incidence of nephropathy reduce and need for dialysis reduced - prevents renal failure
When you start taking them - makes everything look worse
summarise GLP1 analogues
Used for dm and obesity
Liraglutide and siraglutide
Peptides - got to give injection
Stimulate own endogenous insulin production
Showed benefit
Semaglutide -makes wht loss v good for v obese people - cant afford It for obesity though
drugs for DM
Metformin should be given to everyone unless CI
Then can give any of the others
Sulfonylureas are going to be less because cause hypos
Big ones use: SGLT2 and GLP1.
