Cardiology 3 - IHD

Question 1

What is the function of PCSK9?

Answer 1

tags LDL receptors for internalisation. Blocking PCSK9 leads to reduced internalisation of LDL-R.

Question 2

What are examples of PCSK9 inhibitors?

Answer 2

Alirocumab
Evolocumab
Bococizumab

Question 3

What were outcomes in the ODYSSEY LONG TERM trial?

Answer 3

Alirocumab shown to reduce LDL by 61% over placebo in patients at high risk of CV events, already receiving a statin.

Rate of MACE - 3.3 vs 1.7% p = 0.02

Question 4

What were findings in the OSLER trial?

Answer 4

evolocumab vs placebo (70% on statin) - 61% reduction in LDL, with lower rates of cardiac events in the evolocumab group. 50% reduction in post hoc analysis

Question 5

What are side effects of PCSK9 inhibitors?

Answer 5

Higher rates of neurocognitive effects and need to be injected.

Question 6

Have PCSK9 inhibitors been shown to reduce death and AMI?

Answer 6

NO

Question 7

Does raising HDL lower risk of AMI?

Answer 7

NO - torcetrapib has been shown to increase HDL but also mortality

Question 8

What are current indications for statin therapy?

Answer 8

1. 40-75yo persons with 10yr CV risk >7.5%
2. Hx of CV event (MI, Stroke, Angina, PAD, TIA)
3. age >21 with LDL >4.9
4. people with DM

Question 9

What are two regimes for lipid therapy recommended by current guidelines?

Answer 9

High intensity = 80mg atorvastatin or 40mg rosuvastatin

Moderate intensity = 40mg atorvastatin or 20mg rosuvasatatin

Question 10

What patients are recommended high intensity statin therapy?

Answer 10

2ndary prevention = high intensity
LDL >4.9 = high intensity
DM = mod or high intensity
High absolute risk = moderate or high intensity

Question 11

What were outcomes of the PROMISE study?

Answer 11

Compared functional testing vs anatomical testing in patients with Chest pain for Ix (CTCA vs EST/stress echo/nuc med)
composite endpoint - death, MI, hospitalisation for UA, major complication of procedure.

• NS difference in primary endpoint
• NS difference in death or non-fatal MI
• lower rates of patients proceeded to angio without obstructive CAD in the CTCA group

= CTCA viable alternative to stress testing

Question 12

What are features of the coronary calcium score?

Answer 12

Recommended in those at intermediate risk (10-20% over 10 years)
can be useful in patients who are not considered at high risk on traditional RFs
if score = 0 - very low risk of coronary event in 10 years

Question 13

At what cutoff is ischaemia considered on FFR?

Answer 13

FFR

Question 14

What were outcomes of the FAME study?

Answer 14

randomised patients with multi-v CAD to either FFR guided PCI or angiogram guided PCI - composite endpoint MACE

Found improved survival from MACE and reduced MI and death by 35% at 1 year. FFR is now the gold standard for assessing lesions at angiography for planned PCI.

Question 15

What were outcomes of the PLATO study?

Answer 15

ACS patients randomised to either ticagrelor + aspirin or aspirin + clopidogrel

significantly lower rates of MACE (vascular death, MI, stroke) and no significant change in bleeding.

Question 16

What were outcomes of the TRITON study?

Answer 16

randomised ACS patients to either prasugrel or clopidogrel - lower rates of CV death, non fatal MI and stroke at 12 months.

Randomised after coronary anatomy and decision for PCI - issues with generalisability.

Significant increase in major bleeding.

Question 17

What are features of prasugrel and clopidogrel?

Answer 17

both act on P2Y12 ADP receptor.
Prasugrel is a prodrug.
Prasugrel binds irreversibly, ticagrelor is reversible.
ticagrelor causes dyspnoea by adenosine, also ventricular pauses

Question 18

What are contraindications for prasugrel?

Answer 18

prior stroke, weight 75

Question 19

What are features of clopidogrel?

Answer 19

is a pro drug, CPY2C19 metabolism - significant proportion are slow metabolisers - and will hence not respond well to clopidogrel.

Question 20

What are features of the radial approach in PCI?

Answer 20

fewer complications, lower mortality (lower rates of death, MI and stroke)

MATRIX trial.

Question 21

Is there a role for thrombus aspiration following STEMI?

Answer 21

NO

TOTAL trial found that PCI only has lower rates of CV death, MI, cardiogenic shock and class IV failure at 180 days.

Stroke rate was double in the aspiration group.

Question 22

What were outcomes of the PRAMI study?

Answer 22

Patients were randomised to treat only culprit lesion or preventative PCI group following STEMI.

Study was halted as higher rates of MACE in the no preventitive PCI group! composite endpoint was cardiac death, non-fatal MI and refractory ischaemia. (non fatal MI and refractory angina were significant)

RRR 65%, ARR 14%, NNT 7 over 23 months.

Question 23

What were outcomes of the SYNTAX study?

Answer 23

patients with 3VD or left main stenosis were randomised to either CABG or PCI

Rate of MACCE were higher in the PCI group (death, MI and repeat vascularisation), however rates of stroke were significantly lower.

In patients with low complexity disease (low 1/3 syntax score) - difference in event rates were non significant over 5 years. In intermediate, rates were higher in the PCI group (Syntax score >=23)

Death was higher in patients with a syntax score >33.

Question 24

What were outcomes of the freedom study?

Answer 24

compared PCI to CABG in patients with 3vd and diabetes. Primary endpoint was death, non-fatal MI, non-fatal stroke at 12 months.

Found significantly lower rates of MACE in CABG group, also death, Mi and stroke.

Question 25

Given the FREEDOM and SYNTAX studies, what is the appropriate approach to multivessel stable CAD?

Answer 25

If DM - for CABG always.

If no DM and low syntax score, PCI or CABG appropriate, otherwise CABG only.

Question 26

What genetic polymorphisms have been associated with increased risks of coronary artery disease?

Answer 26

Multiple polymorphisms at 9p21 - does not encode for any protein, mechanism is unknown.

Question 27

What is the role of PCI in stable angina?

Answer 27

Does not improve survival - for symptoms only COURAGE trial.

OMT = PCI