Recent Developments in Acute Coronary Syndrome Management
Antiplatelet Therapy: Potent P2Y12 Inhibitors as Standard of Care
For patients with ACS undergoing PCI, prasugrel or ticagrelor should be used instead of clopidogrel as the default P2Y12 inhibitor, combined with aspirin, to reduce cardiovascular death, myocardial infarction, and stroke. 1
Evidence for Potent P2Y12 Inhibitors
Prasugrel and ticagrelor reduce major adverse cardiovascular events by 16-20% compared to clopidogrel in the landmark TRITON-TIMI 38 and PLATO trials, with reductions in stent thrombosis and, for ticagrelor, a nominal reduction in all-cause mortality 1
Both agents increase non-CABG major bleeding compared to clopidogrel, with prasugrel specifically increasing life-threatening bleeds 1
Prasugrel is contraindicated in patients with prior stroke or TIA (6.5% stroke rate vs 1.2% with clopidogrel), and generally not recommended for patients ≥75 years old except in high-risk situations (diabetes or prior MI) 2
Prasugrel dose should be reduced to 5 mg daily in patients <60 kg due to increased bleeding risk 2
Timing of P2Y12 Inhibitor Administration
Routine pretreatment with P2Y12 inhibitors before coronary angiography is not recommended for NSTE-ACS patients undergoing early invasive strategy (<24 hours). 1
In the ACCOAST trial, prasugrel pretreatment (median 4.4 hours before PCI) showed no ischemic benefit but significantly increased bleeding 1
Pretreatment may be reasonable only when angiography timing is anticipated ≥24 hours from loading dose administration 1
For STEMI patients undergoing primary PCI, P2Y12 inhibitors can be administered at time of diagnosis, though most receive them at time of PCI 1
DAPT Duration Strategies: Moving Beyond the 12-Month Standard
Shortened DAPT for High Bleeding Risk
For patients at high bleeding risk who complete 4 weeks of DAPT after successful PCI with drug-eluting stents, switching to single antiplatelet therapy is supported by the MASTER DAPT trial. 1
High bleeding risk is defined as PRECISE-DAPT score ≥25 or meeting ARC-HBR criteria 1
Shortened DAPT (3-6 months) in stable CAD patients undergoing PCI with newer-generation DES showed non-inferiority for MACE but reduced major bleeding compared to 12-24 month durations 3
De-escalation Strategies
De-escalation from ticagrelor or prasugrel to clopidogrel after 1 month post-PCI reduces bleeding without increasing ischemic risk. 1
Both guided (using platelet function testing or genotyping) and unguided de-escalation strategies yield comparable efficacy to standard DAPT while reducing bleeding 1
The TOPIC and TROPICAL-ACS trials demonstrated bleeding reductions with de-escalation at 30 days after PCI for ACS 1
Unguided de-escalation is simpler and avoids the need for platelet function testing, which has shown mixed results in clinical trials 1
Extended DAPT Beyond 12 Months
Prolonged DAPT (18-48 months) reduces myocardial infarction and stent thrombosis but increases major bleeding and potentially all-cause mortality 3
Extended DAPT should be considered only in patients with persistently high ischemic risk and low bleeding risk 1
Proton Pump Inhibitor Co-Administration
PPIs should be administered to all ACS patients at elevated bleeding risk treated with DAPT or oral anticoagulants. 1
The double-blind, placebo-controlled trial showed omeprazole with clopidogrel markedly decreased gastrointestinal bleeding without increasing ischemic events 1
The antiplatelet effects of ticagrelor and prasugrel are not modified by concomitant PPI use, unlike clopidogrel which shows pharmacodynamic attenuation with certain PPIs (most pronounced with omeprazole) 1
Combination with Oral Anticoagulation
For patients requiring chronic anticoagulation who undergo PCI, dual antithrombotic therapy (DOAC plus clopidogrel) is the default strategy, avoiding triple therapy in most cases. 4
Discontinue aspirin at hospital discharge or within 1 week in patients on chronic anticoagulation after PCI 4
Continue clopidogrel (preferred over ticagrelor/prasugrel due to lower bleeding risk) for 6-12 months depending on indication 4
DOACs are preferred over warfarin when combining with antiplatelet therapy due to lower bleeding risk 4
Triple therapy (DAPT plus anticoagulation) may be prolonged up to 1 month only when ischemic risk clearly outweighs bleeding risk 1
Perioperative Management for CABG
Timing of P2Y12 inhibitor discontinuation before CABG varies by agent: 1
Clopidogrel: interrupt 5 days before elective CABG; for urgent CABG, interruption for at least 24 hours is ideal, though proceeding earlier than 5 days may be reasonable 1
Prasugrel: interrupt 7 days before elective CABG; for urgent CABG, interruption for at least 24 hours is ideal, though proceeding earlier than 7 days may be reasonable 1
Ticagrelor: interrupt 3-5 days before elective CABG; for urgent CABG, interruption for at least 24 hours is ideal, though proceeding earlier than 5 days may be reasonable 1
Resume P2Y12 inhibitor 24-72 hours after surgery when bleeding risk is not excessive 1
Common Pitfalls to Avoid
Do not routinely pretreat NSTE-ACS patients with P2Y12 inhibitors before knowing coronary anatomy if early invasive strategy (<24 hours) is planned, as this increases bleeding without clear ischemic benefit 1
Avoid prasugrel in patients with prior stroke/TIA, age ≥75 years (unless high-risk features present), or weight <60 kg without dose reduction 2
Do not withhold PPIs in patients at elevated bleeding risk on DAPT due to concerns about clopidogrel interaction, as bleeding reduction outweighs theoretical ischemic concerns, and ticagrelor/prasugrel are unaffected 1
Avoid prolonging triple antithrombotic therapy beyond 1 week in most patients requiring chronic anticoagulation after PCI, as bleeding risk substantially increases (2-3 fold) without clear ischemic benefit 4
Do not discontinue P2Y12 inhibitors prematurely, particularly in the first few weeks after ACS, as this increases risk of subsequent cardiovascular events 2