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Mechanistic Deep Dive
Vulnerable Plaque
- Thin-cap fibroatheroma (TCFA): cap < 65 ÎŒm + large lipid core
- Detected by OCT (gold standard) or IVUS-NIRS
- PROSPECT, PROSPECT-ABSORB trials â TCFA + plaque burden â MACE
- PREVENT trial 2024 â preemptive PCI of non-flow-limiting vulnerable plaque reduced MACE (CTO + IVUS-guided)
Plaque Erosion
- More common in young women, smokers
- Endothelial denudation without disrupted cap
- EROSION trial: conservative (antithrombotic without stent) feasible if OCT-confirmed erosion
Microcirculatory Injury
- âNo-reflowâ phenomenon during PCI
- Distal embolization, microvascular obstruction
- MVO on CMR predicts adverse outcomes
Recent Trials & Updates
ESC 2023 NSTE-ACS Update
- hs-cTn 0/1h preferred algorithm
- Routine invasive < 24h for high-risk (GRACE > 140)
- Selective invasive acceptable for low-risk
- Ticagrelor preferred over clopidogrel
- Pre-treatment with P2Y12 before angio = NOT routinely recommended (ISAR-REACT 5 + DUBIUS)
ISAR-REACT 5 (2019)
- Prasugrel vs ticagrelor in ACS
- Prasugrel reduced MACE (9.3% vs 6.9%)
- Bleeding similar
- 2024 update: prasugrel may be slightly preferred in NSTEMI-PCI
MASTER DAPT (2021)
- 1 month DAPT vs 12 months in HBR after PCI
- 1 month non-inferior for ischemia, â bleeding
- Foundation for shortened DAPT in HBR
TWILIGHT (2019)
- After 3 mo DAPT, ticagrelor monotherapy (drop ASA)
- Reduced bleeding without â ischemia
- New paradigm: ASA-free maintenance with potent P2Y12
PROSPECT-ABSORB (2020)
- Preemptive PCI of non-flow-limiting vulnerable plaques (TCFA + plaque burden > 70%)
- Bioresorbable scaffold + medical therapy
- Reduced clinical events at 1 year
Targeted Therapies â Lipid
- PCSK9 inhibitors (evolocumab, alirocumab): FOURIER (2017), ODYSSEY OUTCOMES (2018) â â MACE
- Inclisiran (siRNA): ORION trials, q6mo dosing
- Bempedoic acid: CLEAR Outcomes (2023) â â MACE in statin-intolerant
- Lp(a)-lowering (pelacarsen, olpasiran): ongoing trials
Anti-Inflammatory
- CANTOS: canakinumab (anti-IL-1β) â MACE in post-MI + CRP elevation
- COLCOT (2019): colchicine 0.5 mg/d â MACE post-MI
- LoDoCo2 (2020): similar in CCS
- 2023 AHA/ACC IIa for high-risk
High-Yield Specialist Points
Complete vs Culprit-Only Revasc
- COMPLETE trial (2019): STEMI multi-vessel, complete revasc reduced MACE
- NSTE-ACS: less data, but tend toward complete revasc in stable patients
- Staged PCI common
FFR-Guided in NSTE-ACS
- FAMOUS-NSTEMI: FFR led to changes in management in 22%
- FUTURE trial: did not show benefit (stopped early)
- FFR for multivessel disease in stable patients OK
Type 2 MI Management
- Identify and treat trigger (anemia, sepsis, hypertensive crisis)
- Statin + ASA may still benefit
- Routine cath usually NOT indicated unless underlying CAD suspected
- Cardiology consult for risk stratification
MINOCA Workup
- Definition: MI with < 50% stenosis on cath
- ~ 6-15% of all MI
- Workup: OCT/IVUS, CMR, ergonovine if suspect spasm
- Causes: SCAD, vasospasm, embolism, takotsubo, myocarditis, supply-demand
- Tailor therapy to etiology
Sex Differences
- Women with NSTE-ACS: more atypical, delayed presentation, more MINOCA, more SCAD
- Worse outcomes if delayed reperfusion
- Bleeding risk higher
- Microvascular dysfunction more common
Antithrombotic in CKD
- Dose-adjust enoxaparin (1 mg/kg q24h if CrCl < 30)
- Fondaparinux contraindicated if CrCl < 20
- Ticagrelor preferred in CKD (no renal adjustment)
- Bivalirudin can reduce bleeding in CKD
Pearls
- ESC 2023 dropped routine pre-treatment with P2Y12 inhibitor before angiography (except STEMI)
- 0/1h hs-cTn with low-risk clinical features â rapid discharge possible
- Wellens syndrome = critical LAD; do NOT stress test â straight to cath
- De Winter T waves = STEMI equivalent in some literature
- aVR ST elevation + diffuse STâ â donât miss LM/3VD
- Ticagrelor vs prasugrel: prasugrel marginally better (ISAR-REACT 5) but contraindications matter (prior stroke, > 75, < 60 kg)
- MASTER DAPT / TWILIGHT define modern short-DAPT strategies
- Plaque erosion is increasingly recognized â conservative therapy (EROSION trial) being studied