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 aspirin (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 2011 and ESC 2011.

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 (only in patients who have undergone PCI)221, 238 or ticagrelor. All patients, unless contraindicated, should be discharged from hospital on antiplatelet therapy.221, 222, 239-242 Most patients continue taking ASA indefinitely, whereas clopidogrel, prasugrel and ticagrelor are usually given for up to 12 months.

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.

The minimum duration of clopidogrel, prasugrel or ticagrelor therapy depends on whether the patient received a stent during revascularization, and the type of stent.239-242 Although drug-eluting stents have reduced restenosis compared with bare-metal stents, the risk of stent thrombosis persists for longer,239 and clopidogrel, prasugrel or ticagrelor are recommended for up to 1 year in patients with drug-eluting stents.240, 242

Approved antiplatelets for the secondary prevention of ACS

Drug Target Dose/regimen Supporting data
ASA Irreversibly inhibits the COX­1 enzyme 75–325 mg daily Meta-analysis of 195 clinical trials243
Thienopyridine Irreversibly binds to the ADP receptor P2Y12 Clopidogrel: 75 mg daily
Prasugrel: 10 mg daily
CURE (clopidogrel + ASA)448

TRITON-TIMI 38 (prasugrel + ASA)450

TRILOGY ACS (prasugrel vs clopidogrel)462
Ticagrelor Non-thienopyridine: reversibly binds to P2Y12, non­competitively with ADP 90 mg twice daily PLATO (ticagrelor + ASA)279
ACS, acute coronary syndrome; ADP, adenosine diphosphate; ASA, acetylsalicylic acid; CABG, coronary artery bypass graft; CI, confidence interval; COX­1, cyclooxygenase-1; HR, hazard ratio; ICH, intracranial haemorrhage; MI, myocardial infarction; OR, odds ratio; RR, relative risk; TIMI, Thrombolysis in Myocardial Infarction.

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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, 239-242

Guidelines for antiplatelet therapy in the secondary prevention of ACS, indicating year of latest update

  ACCP ACC/AHA ESC
Date of
publication
2012242 2011239 2011221
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 75–162 mg daily indefinitely Clopidogrel 75 mg daily for at least 1 month, ideally up to 12 months ASA 75–100 mg daily continued long term Ticagrelor 90 mg twice if moderate-to-high risk of ischaemic events, prasugrel 10 mg daily if no previous P2Y12 inhibitor and PCI planned, or clopidogrel 75 mg daily if ticagrelor or prasugrel not an option; recommended for 12 months
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 ASA 162–325 mg daily for at least 1 month, then 75–162 mg daily indefinitely Clopidogrel 75 mg daily for at least 1 month, ideally up to 12 months As above
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 ASA 162–325 mg daily for at least 3 months (sirolimus-eluting stent) or 6 months (paclitaxel-eluting stent), then 75–162 mg daily indefinitely Clopidogrel 75 mg daily for at least 12 months As above
Date of
publication
2012242 2009240, 241 2012222
STEMI
No stent As for UA/NSTEMI ASA 75–162 mg daily indefinitely Clopidogrel 75 mg daily for at least 14 days; 1 year recommended ASA 75–100 mg daily indefinitely DAPT with a combination of aspirin and prasugrel or aspirin and ticagrelor is recommended (over aspirin and clopidogrel) in patients treated with PCI.
Bare-metal stent As for UA/NSTEMI ASA 162–325 mg daily for at least 1 month, then 75–162 mg daily indefinitely Clopidogrel 75 mg daily or prasugrel 10 mg daily for a minimum of 1 month; 1 year recommended As above
Drug-eluting stent As for UA/NSTEMI ASA 162–325 mg daily for at least 3 months (sirolimus-eluting stent) or 6 months (paclitaxel-eluting stent), then 75–162 mg daily indefinitely Clopidogrel 75 mg daily or prasugrel 10 mg daily for at least 12 months (beyond 15 months may be considered As above
ACC, American College of Cardiology; ACCP, American College of Chest Physicians; AHA, American Heart Association; ASA, acetylsalicylic acids; 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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