Essence of this Article

Patients are potentially at risk of further ischaemic events for considerable periods after an acute coronary syndrome (ACS) event. Currently, standard of care secondary prevention therapy for patients after ACS is a dual antiplatelet regimen comprising acetylsalicylic acid (ASA) plus clopidogrel, prasugrel or ticagrelor. Although guidelines recommend the indefinite use of ASA after an ACS event, the suggested duration of clopidogrel, prasugrel or ticagrelor therapy varies based on patient characteristics. There are several sets of guidelines for the secondary prevention of ACS, including ACCP 2012, ACC/AHA 2013/2014 and ESC 2011/2012.

Use of antiplatelet therapy in the secondary prevention of acute coronary syndrome

Activated Platelets / Thrombocytes

Activated Platelets / Thrombocytes

Activated platelets and thrombin generation persist for considerable periods after an ACS event, potentially leaving patients at risk of further ischaemic events and providing therapeutic targets for secondary prevention strategies.223, 224, 237 Currently, standard of care secondary prevention therapy for patients after ACS is a dual antiplatelet regimen comprising ASA plus clopidogrel, prasugrel or ticagrelor. All patients, unless contraindicated, should be discharged from hospital on antiplatelet therapy.221, 222, 545, 546, 242 Most guidelines recommend that patients should continue taking ASA indefinitely, whereas clopidogrel, prasugrel and ticagrelor should usually be given for up to 12 months after an ACS event, regardless of the initial management strategy.221, 222, 545, 546, 242

Approved antiplatelets for the secondary prevention of ACS

Drug Target Dose/regimen Supporting data
Acetylsalicylic acid Irreversibly inhibits the COX­1 enzyme 75–325 mg daily Meta-analysis of 195 clinical trials228
Thienopyridine Irreversibly binds to the ADP receptor P2Y12 Clopidogrel: 75 mg daily
Prasugrel: 10 mg daily
CURE (clopidogrel + ASA)229

TRITON-TIMI 38 (prasugrel + ASA)232

TRILOGY ACS (prasugrel vs clopidogrel)244
Ticagrelor Non-thienopyridine: reversibly binds to P2Y12, non­competitively with ADP 90 mg twice daily PLATO (ticagrelor + ASA)231
ACS, acute coronary syndrome; ADP, adenosine diphosphate; COX­1, cyclooxygenase-1.

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Guideline recommendations

There are several sets of guidelines for the secondary prevention of ACS, as well as treatment in the acute phase. Recommendations for the use of antiplatelet therapy are based on clinical trial data for the respective agents.221,222,545,546,242

Guidelines for antiplatelet therapy for the acute, sub-acute and long-term secondary prevention of ACS, indicating year of latest update

  ACCP ESC ACC/AHA
Date of
publication
2012242 2011221 2014545
UA/NSTEMI
No stent ASA 75–100 mg daily Ticagrelor 90 mg twice daily or clopidogrel 75 mg daily Recommended for 12 months After 12 months: ASA 75–100 mg daily or clopidogrel 75 mg daily ASA 150–300 mg loading dose then 75–100 mg daily continued long term, PLUS a P2Y12 inhibitor for 12 months; one of:
  • Ticagrelor 180 mg loading dose then 90 mg twice dailya
  • Prasugrel 60 mg loading dose then 10 mg dailyb,c
  • Clopidogrel 300 mg loading dose then 75 mg dailyd
ASA 162–325 mg promptly after presentation then a maintenance dose of ASA 81–162 mg daily continued indefinitely, PLUS a P2Y12 inhibitor for up to 12 months; one of:
  • Clopidogrel 300 or 600 mg loading dose then 75 mg daily
  • Ticagrelor 180 mg loading dose then 90 mg twice dailye
Bare-metal stent ASA 75–100 mg daily Ticagrelor 90 mg twice daily, clopidogrel 75 mg daily or prasugrel 10 mg daily Recommended for 12 months, minimum 1 month After 12 months: ASA 75–100 mg daily or clopidogrel 75 mg daily As above ASA 162–325 mg promptly after presentation then a maintenance dose of 81–325 mg daily continued indefinitely,f PLUS a P2Y12 inhibitor for at least 12 monthsf or beyond; one of:
  • Clopidogrel 300 or 600 mg loading dose then 75 mg daily
  • Prasugrel 60 mg loading dose then 10 mg dailyc
  • Ticagrelor 180 mg loading dose then 90 mg twice dailye
Drug-eluting stent ASA 75–100 mg daily Ticagrelor 90 mg twice daily, clopidogrel 75 mg daily or prasugrel 10 mg daily Recommended for 12 months, minimum 3–6 months After 12 months: ASA 75–100 mg daily or clopidogrel 75 mg daily As above As for bare-metal stent
Date of
publication
2012242 2012222 2013546
STEMI
No stent As for UA/NSTEMI For patients who did not receive reperfusion therapy:
ASA 150–500 mg loading dose, then 75–100 mg daily indefinitely, PLUS clopidogrel 75 mg daily for at least 1 month and up to 12 months

For patients who underwent fibrinolysis:
ASA 150–500 mg loading dose, then 75–100 mg daily indefinitely, PLUS clopidogrel loading dose of 300 mg then 75 mg daily for up to 12 months

For patients who underwent PCI without stent placement:i
ASA 150–500 mg loading dose, then 75–100 mg daily indefinitely, PLUS a P2Y12 inhibitor for up to 12 months; one of:
  • Clopidogrel 600 mg loading dose then 75 mg daily
  • Prasugrel 60 mg loading dose then 10 mg dailyc,j,k
  • Ticagrelor 180 mg loading dose then 90 mg twice daily
For selected patients who receive ASA and clopidogrel:
Low-dose rivaroxaban (2.5 mg twice daily) may be considered if the patient is at low risk of bleeding
For patients who underwent fibrinolysis:
ASA 162–325 mg loading dose then maintenance dose of 81–325 mg daily continued indefinitely,f PLUS clopidogrel loading dose of 300 mgh then 75 mg daily for at least 14 days and up to 12 months

For patients who underwent PCI without stent placement – recommendations as for those listed for Bare-metal stent
Bare-metal stent As for UA/NSTEMI As recommended for patients who underwent PCI without stent placement – dual antiplatelet therapy with ASA plus a P2Y12 inhibitor must be continued for up to 12 months with a strict minimum of 1 month ASA 162–325 mg loading dose then 81–325 mg daily indefinitely,f PLUS a P2Y12 inhibitor for 12 months; one of:
  • Clopidogrel 600 mg loading dose then 75 mg daily
  • Prasugrel 60 mg loading dose then 10 mg dailyc
  • Ticagrelor 180 mg loading dose then 90 mg twice dailye
Drug-eluting stent As for UA/NSTEMI As recommended for patients who underwent PCI without stent placement – dual antiplatelet therapy with ASA plus a P2Y12 inhibitor must be continued for up to 12 months with a strict minimum of 6 months As above, although treatment with P2Y12 inhibitor may be continued beyond 12 months
aTicagrelor is recommended for all patients at moderate-to-high risk of ischaemic events (e.g. elevated troponins), regardless of initial treatment strategy and including those pre-treated with clopidogrel (which should be discontinued when ticagrelor is commenced); bprasugrel is recommended for P2Y12-inhibitor-naïve patients in whom coronary anatomy is known and who are proceeding to PCI unless there is a high risk of life-threatening bleeding or other contraindications; cprasugrel is contraindicated in patients with a history of stroke or transient ischaemic attack; dclopidogrel is recommended for patients who cannot receive ticagrelor or prasugrel; eif ticagrelor is given, the recommended maintenance dose of ASA is 81 mg daily; fthe preferred maintenance dose of ASA is 81 mg daily; gif the risk of morbidity from bleeding outweighs the anticipated benefit of a recommended duration of P2Y12 inhibitor therapy after stent implantation, earlier discontinuation (e.g. <12 months) of P2Y12 inhibitor therapy is reasonable; ha 300 mg loading dose for patients ≤75 years of age only; for patients >75 years old a 75 mg dose should be given; ifor patients who underwent PCI dual antiplatelet therapy with ASA and prasugrel or ASA and ticagrelor is recommended over ASA and clopidogrel; jin patients with a body weight of <60 kg, a 5 mg daily maintenance dose of prasugrel is recommended; kprasugrel is not generally recommended in patients ≥75 years old, but a maintenance dose of 5 mg daily should be used if treatment is deemed necessary;
ACC, American College of Cardiology; ACCP, American College of Chest Physicians; AHA, American Heart Association; ASA, acetylsalicylic acid; ESC, European Society of Cardiology; NSTEMI, non-ST-segment elevation myocardial infarction; PCI, percutaneous coronary intervention; STEMI, ST-segment elevation myocardial infarction; UA, unstable angina.

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