• Morphine: may be useful if pain is severe, but give the minimum necessary dose and monitor BP and ventilation. Its theoretical benefit is reduced preload, heart rate, and myocardial oxygen demand. Goodman & Gilman notes that it can cause peripheral vasodilation and hypotension, especially in volume-depleted patients.
• Fentanyl: often preferred when fast titration and greater hemodynamic stability are desired, but it is not proven superior for MI outcomes and still interferes with oral P2Y12 absorption.
• In a hypotensive, bradycardic, hypovolemic, or respiratory-compromised MI patient, avoid or use either opioid with exceptional caution.

Current ACS guideline summary

1. Immediate assessment and stabilization

• Obtain and interpret a 12-lead ECG promptly, with serial ECGs if the first is nondiagnostic.
• Use high-sensitivity troponin with a validated serial testing pathway.
• Continuous monitoring for arrhythmia and instability.
• Give oxygen only for hypoxemia or respiratory distress, not routinely in normoxemic patients.
• Treat ongoing ischemia with anti-ischemic therapy when appropriate, while avoiding nitrates in hypotension, right-ventricular infarction, or recent phosphodiesterase-5 inhibitor use.
• Opioids should be reserved for severe refractory pain or distress. Both morphine and fentanyl can delay absorption of oral P2Y12 inhibitors.

2. Reperfusion and invasive strategy

• Primary PCI is the preferred reperfusion method when timely available.
• If timely PCI is not feasible, fibrinolysis may be appropriate in eligible patients, followed by transfer to a PCI-capable center.
• In multivessel STEMI, complete revascularization is recommended, either during the index procedure or as a staged approach.
• In cardiogenic shock, urgently revascularize the culprit artery. Do not routinely perform immediate PCI of non-culprit arteries.

• Intermediate- or high-ischemic-risk patients should undergo invasive assessment during hospitalization with intent to revascularize as indicated.
• Very-high-risk features, such as hemodynamic instability/shock, recurrent refractory ischemia, life-threatening arrhythmias, acute heart failure due to ischemia, or dynamic ST changes, require an immediate invasive strategy.
• Low-risk patients can have a selective invasive strategy guided by further risk assessment.

3. Antithrombotic treatment

• Aspirin plus a P2Y12 inhibitor is standard for ACS unless contraindicated.
• For ACS patients undergoing PCI, ticagrelor or prasugrel is preferred over clopidogrel when there is no contraindication.
• Default duration of DAPT is at least 12 months in patients not at high bleeding risk.
• Tailor duration and intensity for bleeding versus ischemic risk. Shorter DAPT or P2Y12 monotherapy may be appropriate in selected high-bleeding-risk patients after PCI.
• For patients who also need long-term oral anticoagulation, minimize triple therapy. The guideline supports stopping aspirin after 1 to 4 weeks and continuing an oral anticoagulant plus a P2Y12 inhibitor, usually clopidogrel.
• Use procedural anticoagulation during PCI, chosen according to the clinical setting and local protocol.

4. PCI technique

• Prefer radial access over femoral access to reduce bleeding, vascular complications, and mortality.
• Use intravascular imaging to guide PCI in complex coronary lesions when feasible.

5. Lipid lowering

• Start or continue a high-intensity statin in all ACS patients, early in the course.
• Ezetimibe may be started concurrently in appropriate patients.
• If LDL-C remains ≥70 mg/dL (1.8 mmol/L) despite maximally tolerated statin therapy, add a non-statin lipid-lowering agent such as ezetimibe or a PCSK9-targeting therapy.
• Further intensification is reasonable even at LDL-C 55 to <70 mg/dL in this very-high-risk population.
• Recheck lipids 4 to 8 weeks after starting or changing therapy. This emphasis on early combination lipid treatment is a notable feature of the 2025 guideline.

6. Secondary prevention before discharge

• Cardiac rehabilitation referral, including home-based rehabilitation when needed.
• Smoking cessation, BP control, diabetes management, weight/activity counseling, and vaccination as appropriate.
• Individualize beta-blocker use. Long-term routine beta-blocker therapy is not automatically needed for everyone with preserved LV function; it is most clearly indicated with reduced LVEF, heart failure, recurrent angina, arrhythmia, or another indication.
• Start guideline-directed therapy for heart failure or reduced LVEF when present.
• Clear discharge plan, medication adherence counseling, and early follow-up.

Practical one-line algorithm