Acute coronary syndromes 1 and antiplatelet drugs

Question 1

Acute coronary syndrome is an umbrella term. which conditions does it include? (2)

Answer 1

1) Unstable angina

2) MI with or without ST-segment elevation

Question 2

Patients with different types of ACS may present with similar symptoms. How is definitive diagnosis made?

Answer 2

On the basis of clinical presentation, ECG changes and measurements of biochemical cardiac markers

Question 3

Explain how unstable angina and non-ST-segment elevation myocardial infarction (NSTEMI) occur

Answer 3

These conditions are related and usually occur when an atheromatous plaque ruptures. Its often characterised by stable angina that suddenly worsens, recurring or prolonged angina at rest or new onset of severe angina.
↳Without treatment, it can progress to serious heart damage or STEMI.

Question 4

Outline the differences between unstable angina and NSTEMI

Answer 4

1) patients with unstable angina have no evidence of myocardial necrosis
2) In NSTEMI myocardial necrosis will be present (although less than with STEMI)
↳detected by elevation of troponin, unstable angina will have normal serial troponin

Question 5

what are the treatment aims of unstable angina and NSTEMI

Answer 5

These conditions are managed similarly:

1) provide supportive care
2) pain relief during acute attack
3) prevent further cardiac events and death

Question 6

outline the initial management of NSTEMI and unstable angina

Answer 6

1) Oxygen - if evidence of hypoxia or pulmonary oedema
2) Nitrates- to relieve ischemic pain
↳IV Diamorphone or morphine if pain continues and an antiemetic e.g. Metoclopramide or cyclizine
3) Aspirin 300mg, AND clopidogrel should also be given.
↳ prasugrel and ticagrelor are alternatives to clopidogrel
4) Heparin (unfractionated) OR LMWH OR Fondaparinux
5) B-blockers in all if not C/I (continued indefinitely)
↳ diltiazem/verapamil alternatives if BB not tolerated or in those WITHOUT left ventricular dysfunction
6) Glycoprotein IIb/IIIa inhibitors eptifibatide and tirofiban (with heparin + antiplatelet) in those high risk of MI/death
↳ in intemediate/high risk abciximab (or Bivalirudin in who early intervention is planned)
7) Revascularisation procedures often appropriate

Question 7

explain the cause and characteristics of an ST-segment elevation myocardial infarction (STEMI)

Answer 7

Atheromatous plaque rupture leads to thrombosis and myocardial ischemia with irreversible necrosis of heart muscle often leading to long term complications

Question 8

Outline the initial and long term management of a STEMI

Answer 8

1) Oxygen, nitrates and diamorphine/morphine provide initial support and pain relief
2) Aspirin and percutaneous coronary intervention or thrombolytics promote reperfusion
3) Anticoagulants help to reduce re-occlusion and systemic embolisation
4) long term use of aspirin, B-blockers, ACEi and statins help to reduce mortality further

Question 9

ACEi (or ARB if intolerated) have been shown to be of benefit in those with STEMI. When should they be initiated and how long should they continue being taken for?

Answer 9

In those with hypertension and also those with normal blood pressure, treatment with ACEi (or ARB) can be started within 24 hours of MI and continued for at least 5-6w
↳(early administration of B-Blockers has been shown to be of benefit in STEMI and should be initiated if not C/I)

Question 10

outline the long term management of STEMI

Answer 10

involves several drugs which should ideally be started before patient is discharged
1) aspirin to all patients unless C/I
↳ addition of clopidogrel shown to reduce mortality, warfarin is an alternative and so is rivaroxiban
2) B-Blockers should be given to all unless C/I.
↳ acebutolol, metoprolol, propranolol are suitable
↳ Bisoprolol and carvedilol in left ventricular dysfunction
↳ dilt/verap if B-Blocker C/I (but not in left ventri dysfun)
3) ACEi (or ARB) in all patients esp in left ventricular dys
4) Nitrates in all patients with angina
5) statins

Question 11

in patients with unstable angina or NSTEMI, clopidogrel is given in combination with aspirin. How long should this be given for?

Answer 11

Up to 12 months. most benefit occurs during first 3 months (Aspirin should be continued indefinitely)
↳ prasugrel or ticagrelor are alternatives
↳ (ACEi should also be given)

Question 12

when is rivaroxiban licensed in ACS, and what can it be given in combination with?

Answer 12

low dose in combination with aspirin alone or aspirin and clopidogrel is licensed for prevention of atherothrombotic events following ACS with elevated cardiac biomarkers

Question 13

list 3 ADP-receptor antagonists and outline the MoA of these drugs

Answer 13

1) Clopidogrel, ticagrelor, prasugrel
2) prevent platelet aggregation in ARTERIES where platelet-rich thrombus can form leading to possible occlusion. These antiplatelet drugs bind irreversibly to ADP receptors on the surface of platelets preventing aggregation.

Question 14

Explain why ADP-receptor antagonists have a synergistic effect when given with aspirin

Answer 14

ADP-receptor antagonists bind to ADP receptors on platelets, this process is independent of the COX pathway

Question 15

what are the most common adverse effects of ADP-receptor antagonists?

Answer 15

1) Haemorrhage- esp serious if GI or intracranial
2) GI upset, including dyspepsia abdominal pain and diarrhoea
3) anemia, skin reactions
4) rarely thrombocytopenia

Question 16

who whould ADP-receptor antagonists be used in caution with?

Answer 16

1) Do not use in those with significant active bleeding. May need to be stopped 7d before elective surgery
2) used in caution in people with hepatic/renal impair

Question 17

why might the efficacy of clopidogrel be reduced by CYP inhibitors?
2) Give examples of CYP 450 inhibitors that would interact with clipidogrel

Answer 17

1) Its a pro-drug that requires metabolism by CYT P450 to its active form to have antiplatelet effect.
2) Omeprazole, ciprofloxacin, erythromycin, some antifungals and SSRIs

Question 18

Because Clopidogrel interacts with omeprazole, what alternative PPI’s can be given instead?

Answer 18

where GI protection with PPI is required, lansoperazole or pantoprazole are preferred as they less likely to inhibit clopidogrel activation

Question 19

what are the important interactions to be aware of with regards to ADP-receptor antagonists?

Answer 19

1) Co-prescription with other antiplatelet drugs, anticoagulants (e.g. heparin) or NSAIDs increase risk of bleeding
2) CYP P450 inhibitors and inducers. Although ticagrelor is not a Pro-drug but still interacts which could lead to increased bleeding if given with CYP inhibitors
↳ prasugrel is a prodrug but less susceptible to interactions

Question 20

How long does it take for clopidogrel to reach its full antiplatelet effect and how is it dosed in ACS?

Answer 20

1) low doses require up to a week to reach full effect
2) if rapid effect needed (e.g. in STEMI/NSTEMI) a loading dose 300mg is given initially and then maintenance dose of 75mg daily (with or without food)