Introduction
2015 ESC guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation [4] | 2014 ESC/EACTS Guidelines on myocardial revascularization [3] | ||||
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Recommendations for platelet inhibition in non-ST-elevation acute coronary syndromes | Recommendations for antithrombotic treatment in patients with STEMI undergoing primary PCI | ||||
RC | RL | RC | RL | ||
Aspirin is recommended for all patients without contraindications at an initial oral loading dosed of 150–300 mg (in aspirin-naive patients) and a maintenance dose of 75–100 mg/day long-term regardless of treatment strategy | I | A | ASA is recommended for all patients without contraindications at an initial oral loading dose of 150–300 mg (or 80–150 mg i. v.) and at a maintenance dose of 75–100 mg daily long-term regardless of treatment strategy | I | A |
A P2Y12 inhibitor is recommended, in addition to aspirin, for 12 months unless there are contraindications such as excessive risk of bleeds | I | A | A P2Y12 inhibitor is recommended in addition to ASA and maintained over 12 months unless there are contraindications such as excessive risk of bleeding. Options are: | I | A |
– Ticagrelor (180 mg loading dose, 90 mg twice daily) is recommended, in the absence of contraindicationsa, for all patients at moderate-to-high risk of ischaemic events (e. g. elevated cardiac troponins), regardless of initial treatment strategy and including those pretreated with clopidogrel (which should be discontinued when ticagrelor is started) | I | B | – Ticagrelor (180 mg loading dose, 90 mg twice daily) if no contraindication | I | B |
– Prasugrel (60 mg loading dose, 10 mg daily dose) is recommended in patients who are proceeding to PCI if no contraindicationa
| I | B | – Prasugrel (60 mg loading dose, 10 mg daily dose) if no contraindication | I | B |
– Clopidogrel (300–600 mg loading dose, 75 mg daily dose) is recommended for patients who cannot receive ticagrelor or prasugrel or who require oral anticoagulation | I | B | – Clopidogrel (600 mg loading dose, 75 mg daily dose), only when prasugrel or ticagrelor are not available or are contraindicated | I | B |
It is not recommended to administer prasugrel in patients in whom coronary anatomy is not known | III | B | It is recommended to give P2Y12 inhibitors at the time of first medical contact | I | B |
P2Y12 inhibitor administration for a shorter duration of 3–6 months after DES implantation may be considered in patients deemed at high bleeding risk | IIb | A | |||
P2Y12 inhibitor administration in addition to aspirin beyond 1 year may be considered after careful assessment of the ischaemic and bleeding risks of the patient | IIb | A |
Rationale for prolonged DAPT
Risk and benefit of prolonged DAPT
Extended DAPT with ticagrelor 60 mg twice daily (PEGASUS-TIMI-54 study)
Study population, study medication, endpoints
Results
Efficacy data
Safety data
Further analyses
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The rate of haemorrhage resulting in irreversible damage or death was < 1 % in all groups over the three-year period, without any statistically significant difference between ticagrelor and the placebo group.
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The analysis of the primary efficacy endpoint in combination with the primary safety endpoint of TIMI major bleedings showed no significant difference between ticagrelor and placebo. However, in terms of the combined benefit/safety analysis of ischaemic endpoints and bleeding events with irreversible damage (i. e. intracranial and fatal haemorrhage), prolonged DAPT with ticagrelor 60 mg twice daily demonstrated a benefit in comparison with placebo [21].
Recommendation for the use of prolonged DAPT with ticagrelor 60 mg twice daily/ASA 100 mg in patients following myocardial infarction
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Patient selection: The prerequisite for the indication of prolonged DAPT is the individual evaluation of the ischaemic and bleeding risk. Prolonged DAPT is recommended accordingly in patients demonstrating one of the following characteristics: Stent thrombosis, re-infarction, complex coronary anatomy, complex intervention, overt diabetes mellitus, peripheral arterial disease (PAD), non-end stage chronic kidney disease (especially stage III) (see Fig. 7). Regardless of cardiovascular risk, the following patients should rather not receive prolonged DAPT: Patients with a history of haemorrhage or at high risk of haemorrhage (e. g. a CRUSADE score > 40) [23], a history of TIA or stroke, patients on oral anticoagulant therapy or under continuous treatment with nonsteroidal anti-inflammatory drugs (NSAIDs), frail patients, patients with malignancies and patients with stage IV–V chronic renal disease.
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Indication:1.In an acute event by the treating interventional cardiologist: The main indication for prolonged DAPT with ticagrelor 60 mg twice daily should be determined at the time of the acute event, documented in the discharge letter and explanatory argument. This is an easy timepoint at which the complexity of the intervention and of the coronary anatomy can be assessed.2.By the rehabilitation physician: Inpatient/outpatient rehabilitation offers a good opportunity to inform patients about the value of prolonged DAPT if the decision was not made at the acute hospital, and the initial tolerability of DAPT can be assessed under medical supervision.3.Within one year from the acute event, e. g. by a resident specialist for internal medicine: Before the end of the standard 12-month DAPT, the initial indication for prolonged DAPT with ticagrelor 60 mg twice daily should be reassessed on the basis of the tolerability of the now almost one-year DAPT (no clinically significant haemorrhage) and the persistently high ischaemic risk. If indicated, the prolonged DAPT should be continuously prescribed.
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Notes for primary care providers:
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When using ticagrelor in the first year after myocardial infarction, the recommended dose is 90 mg twice daily [2‐6]. The corresponding dose for prasugrel is 10 mg once daily (except in elderly and low weight patients in whom a dose reduction to 5 mg is recommended) and for clopidogrel 75 mg once daily in this first year. Prolonged DAPT with ticagrelor has been approved at a dose of 60 mg twice daily.
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At 12 months following ACS, ticagrelor 90 mg twice daily, prasugrel 10 mg once daily or clopidogrel 75 mg once daily can be switched directly to ticagrelor 60 mg twice daily (with no loading dose). As far as possible, DAPT with ticagrelor 60 mg twice daily should be continued without interruption following the 12-month DAPT after ACS.
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Ticagrelor 60 mg twice daily is permitted as part of prolonged DAPT provided that therapy is initiated within two years after the acute event or within one year after the end of a preceding course of DAPT.
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Ticagrelor 60 mg twice daily is permitted for long-term therapy; study data over a period of three years is available.
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