ChemPath: Brief Lipid Update Flashcards
What is the optimal medical therapy for people with coronary heart disease?
- Intensive lifestyle modification
- Aspirin
- High-dose statin (atorvastatin 40-80mg OD)
- Optimal blood glucose control
- Thiazides
- Assessment for probable T2DM
key message = aggressive management of blood pressure and lipids improves survival.
What is the statistical mortality benefit of adding a thiazide diuretic to outstanding BP medications, following an MI?
Worth it, as 2 in 100 will be prevented from a further MI in the next 5 years
Shown by the SPRINT Study
List some options for people with statin intolerance.
- Ezetemibe (reduced absorpotion)
- Plasma exchange
- PCSK9 inhibitors
NOTE: niacin is no longer available
Describe the function of PCSK9 and PCSK9 inhibitor
- PCSK9 targets the LDL receptor (LDLR) leading to its endocytosis and their degradation
- This reduces the ability of the liver to take up cholesterol from the blood
- Threfore a PCSK9 inhibitor prevents the action of PCSK9, resultin in increased levels of LDLRs which uptake LDLs and reduce its serum level.
Name a PCSK9 inhibitor.
Evolocumab
Which patient group may benefit from PCSK9 inhibitors?
Patients who are at very high risk (e.g. familial hypercholesterolaemia)
Statin-intolerant patients
NOTE: PCSK9 inhibitors reduce the incidence of cardiovascular events but has NO effect on mortality, and has a high Number Needed to Treat (NNT) (Fourier study)
How long does it take to see benefit from good glucose control?
15 years of good glucose control in newly diagnosed T2DM before you see a reduction in complications
Shown by the UKPDS study
What is the legacy effect?
A period of good glycaemic control will have a beneficial effect on mortality for up to 10 years even if the patient reverts to poor glycaemic control after a certain period of time.
Shown by the UKPDS study
What did the DCCT study show?
Good control in type 1 diabetes improves outcomes
*Legacy effect was shown here too like the UKPDS study. but the UKPDS focussed on T2DM, the DCCT focused on T1DM*
What did the Advance study show?
Targeting HbA1c of less than 6.5% reduces microvascular events
Intensive glucose control was associated with an increased risk of severe hypoglycaemia and hospitalisation BUT no increased risk of mortality (unlike Accord study)
What are the effects of sudden aggressive blood glucose control in patients with long-standing poor glycemic control and cardiovascular complications?
- Reduced the incidence of complications
- Increased mortality (likely due to precipitating tachycardia and arrhythmias)
Really important to consider whether the patient has atheromas to begin with before suddenly tightening glucose control
This was found by the ACCORD trial
Describe how SGLT2 inhibitors can reduce blood glucose.
Increases urinary excretion of glucose by inhibiting re-uptake –> causes a reduction in blood glucose and blood pressure. It also helps loose weight!
NOTE: this can also be used in heart failure because of its diuretic effect
Main side-effects: UTIs due to glycosuria, rarely DKA
Name an SGLT2 inhibitor
Empagliflozin
What were the key findings of the EMPA-REG study?
Significant reduction in mortality after just 4 years of using Empagliflozin.
Reduces HbA1c
Treats heart failure due to diuresis
Prevents nephropathy as it reduces albuminuria by letting glucose pass into the tubules instead - protects the kidneys (initial sharp reduction in GFR but then recovers)
*Albumin is poisonous to the kidneys so these SGLT2 inhibitors are renal-protective*
What side-effect finding in the CANVAS study was then not seen in the EMPA-REG, OBSERVE-4D and DECLARE study
CANVAS study found that the use of canagliflozin (an SGLT2 inhibitor) increased amputation risk.
OBSERVE-4D did not see any evidence for excess amputations with canagliflozin.
DECLARE did not see it either with Dapagliflozin (in fact it saw that Dapagliflozin reduced CVD death and hospitalisation for heart failure)
**EMPA-REG **did not see any increased risk of amputations with empagliflozin.
