Treatment of acute coronary syndromes (ACS) is designed to relieve distress, interrupt thrombosis, reverse ischemia, limit infarct size, reduce cardiac workload, and prevent and treat complications. An ACS is a medical emergency; outcome is greatly influenced by rapid diagnosis and treatment. Treatment occurs simultaneously with diagnosis. Treatment includes revascularization (with percutaneous coronary intervention [PCI], coronary artery bypass grafting [CABG], or fibrinolytic therapy) and pharmacologic therapy to treat ACS and underlying coronary artery disease.
Medications used depend on the type of ACS and include:
Antiplatelet therapy: Aspirin and P2Y12 inhibitors (clopidogrel, prasugrel, ticagrelor, cangrelor)
Nitroglycerin (sublingual or IV) and sometimes opioids
Anticoagulation (unfractionated or low molecular weight heparin) or bivalirudin (particularly in patients with ST-segment elevation myocardial infarction [STEMI] who are at high risk of bleeding)
Glycoprotein IIb/IIIa inhibitor for certain patients undergoing PCI and high-risk lesions (eg, high thrombus burden, no reflow)
Fibrinolytics for select patients with ST-segment elevation myocardial infarction (STEMI) when timely PCI unavailable
Beta-blocker
Statins and sometimes other lipid-lowering agents
Angiotensin-converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB)
Sometimes sodium-glucose-cotransporter 2 (SGLT2) inhibitor
Sometimes mineralocorticoid receptor antagonist (MRA)
Antiplatelet and antithrombotic medications, which stop clots from forming, are used routinely. Anti-ischemic medications (eg, beta-blockers, IV nitroglycerin) are frequently added, particularly when chest pain or hypertension is present (see table ).
If primary PCI is not immediately available, fibrinolytics should be used if not contraindicated for STEMI, but fibrinolytics worsen outcome for unstable angina and non-ST elevation myocardial infarction (NSTEMI) (1).
Chest pain can be treated with nitroglycerin or sometimes morphine or fentanyl. Nitroglycerin is preferable to morphine or fentanyl, which should be used judiciously (eg, if a patient has a contraindication to nitroglycerin or is in pain despite nitroglycerin therapy). Nitroglycerin is initially given sublingually, followed by continuous IV drip if needed. Morphine is highly effective but can depress respiration, can reduce myocardial contractility, and is a potent venous vasodilator. Evidence also suggests that morphine and fentanyl interfere with some P2Y12 receptor inhibitors (2, 3, 4). A large retrospective trial showed that morphine may increase mortality in patients with acute myocardial infarction (3, 4). Hypotension and bradycardia secondary to opioids can usually be overcome by prompt elevation of the lower extremities.
Blood pressure (BP) is normal or slightly elevated in most patients on arrival at the emergency department; BP gradually falls over the next several hours. Continued hypertension requires treatment with antihypertensives, preferably IV nitroglycerin, to lower BP and reduce cardiac workload. Severe hypotension or other signs of shock are ominous and must be treated aggressively with IV fluids and sometimes vasopressors.
Post-acute management typically includes beta blockers and aggressive lipid management with statins and other agents. Longer-term therapy includes continuation of antiplatelet therapy, renin-angiotensin system inhibition with an ACE inhibitor or ARB, and sometimes a MRA, SGLT2 inhibitor, or colchicine.
See also Treatment of Stable Angina, Treatment of Acute Coronary Syndromes, Treatment of Unstable Angina, and Treatment of Acute Myocardial Infarction for more details on the clinical pharmacologic approach to each condition; and table and the text below for more information about specific medications.
Medications for Coronary Artery Disease*
Medication | Dosage | Use |
|---|---|---|
Angiotensin-converting enzyme (ACE) inhibitors | ||
Benazepril Captopril Enalapril Fosinopril Lisinopril Moexipril Perindopril Quinapril Ramipril Trandolapril | Variable† | All patients with CAD, especially those with large infarctions, renal insufficiency, heart failure, hypertension, or diabetes Contraindications include hypotension, hyperkalemia, bilateral renal artery stenosis, pregnancy, and known allergy |
Angiotensin II receptor blockers (ARBs) | ||
Candesartan Eprosartan Irbesartan Losartan Olmesartan Telmisartan Valsartan | Variable† | An effective alternative for patients who cannot tolerate ACE inhibitors (eg, because of cough); currently, not first-line treatment after MI Contraindications include hypotension, hyperkalemia, bilateral renal artery stenosis, pregnancy, and known allergy |
Anticoagulants: Direct-acting oral anticoagulants‡ | ||
Apixaban | 5 mg orally twice a day | May be useful long-term in patients with non-valvular atrial fibrillation |
Dabigatran | 150 mg orally twice a day (or 110–150 mg orally twice a day for patients also taking P2Y12 inhibitors) | |
Edoxaban | 60 mg orally once a day | |
Rivaroxaban | 20 mg orally once a day (or 15 mg orally once a day for patients also taking P2Y12 inhibitors) | |
Anticoagulants: Direct thrombin inhibitors | ||
Argatroban | 350 mcg/kg (IV bolus) followed by 25 mcg/kg/minute (IV infusion) | As an alternative to heparin in patients with ACS and a known or suspected history of heparin-induced thrombocytopenia |
Bivalirudin | Variable† | |
Anticoagulants: Factor Xa inhibitor | ||
Fondaparinux | 2.5 mg subcutaneously every 24 hours | As an alternative to heparin in patients with ACS and a known or suspected history of heparin-induced thrombocytopenia |
Anticoagulants: Low molecular weight heparins | ||
Dalteparin Enoxaparin¶ Tinzaparin | Variable† | Patients with unstable angina or NSTEMI Patients < 75 years receiving tenecteplase Almost all patients with STEMI as an alternative to unfractionated heparin (unless PCI is indicated and can be done in < 90 minutes); drug continued until PCI or CABG is done or patient is discharged |
Anticoagulants: Unfractionated heparin | ||
Unfractionated heparin | Patients with unstable angina or NSTEMI: 60–70 units/kg IV (maximum, 5000 units; bolus), followed by 12–15 units/kg/hour (maximum, 1000 units/hour) for 48 hours or until PCI is complete Patients with STEMI: 60 units/kg IV (maximum, 4000 units; bolus) given when alteplase, reteplase, or tenecteplase is started, then followed by 12 units/kg/hour (maximum, 1000 units/hour) for 48 hours or until PCI is complete | Patients with unstable angina or NSTEMI as an alternative to enoxaparin Patients who have STEMI and undergo urgent angiography and PCI or patients > 75 years receiving tenecteplase |
Anticoagulants: Vitamin K inhibitor | ||
Warfarin | Oral dose adjusted to maintain INR of 2–3 | Recommended for primary prevention in patients at high risk of systemic emboli (ie, with atrial fibrillation, mechanical heart valves, venous thromboembolism, hypercoagulable disorders, or LV thrombus) May be useful for primary prevention in patients with STEMI and anterior wall akinesis or dyskinesis if risk of bleeding is low Reasonable for patients with asymptomatic mural thrombus |
Antiplatelet agents | ||
Aspirin | For stable angina†: 75 or 81 mg orally once a day (enteric-coated) For ACS: 160–325 mg orally chewed (not enteric-coated) on arrival at emergency department and once a day thereafter during hospitalization and 81 mg§ orally once a day long-term after discharge | All patients with CAD unless aspirin is not tolerated or is contraindicated; used long-term |
Clopidogrel | 75 mg orally once a day For patients undergoing PCI: 300–600 mg orally once, then 75 mg orally once a day for 1–12 months | Used with aspirin or, in patients who cannot tolerate aspirin, alone For elective PCI, maintenance therapy required for at least 1 month for bare-metal stents and for at least 6–12 months for drug-eluting stents For ACS, dual antiplatelet therapy (typically with aspirin) is recommended for at least 12 months (for any type of stent) |
Prasugrel | 60 mg orally once before PCI, followed by 10 mg orally once a day for 1–12 months | Only for patients with ACS undergoing PCI Not used in combination with fibrinolytic therapy |
Ticagrelor | For patients undergoing PCI: 180 mg orally once before the procedure, followed by 90 mg orally twice a day for 1–12 months | — |
Ticlopidine | 250 mg orally twice a day for 1–12 months | Rarely used routinely because neutropenia is a risk and white blood cell count must be monitored regularly |
Beta-blockers | ||
Atenolol | Variable† | All patients with ACS, unless a beta-blocker is not tolerated or is contraindicated, especially high-risk patients; used long-term Intravenous beta-blockers may be used in patients with ongoing chest pain despite usual measures, or persistent tachycardia, or hypertension in patients with unstable angina and myocardial infarction. Caution is necessary in patients with hypotension or other evidence of hemodynamic instability. |
Bisoprolol | Variable† | |
Carvedilol | Variable† | |
Metoprolol | Variable† | |
Calcium channel blockers | ||
Amlodipine | Variable† | Patients with stable angina if symptoms persist despite nitrates use or if nitrates are not tolerated |
Diltiazem (extended-release) | Variable† | |
Felodipine | Variable† | |
Nifedipine (extended-release) | Variable† | |
Verapamil (extended-release) | Variable† | |
Glycoprotein IIb/IIIa inhibitors | ||
Abciximab | Variable† | Some patients with ACS, particularly those who are having PCI with stent placement and high-risk patients with unstable angina or NSTEMI and large thrombus burden Therapy started during PCI and continued for 6–24 hours thereafter |
Eptifibatide | Variable† | |
Tirofiban | Variable† | |
Nitrates: Short acting | ||
Sublingual nitroglycerin (tablet or spray) | 0.3–0.6 mg every 4–5 minutes up to 3 doses | All patients for immediate relief of chest pain; used as needed |
Nitroglycerin as continuous IV drip | Started at 5 mcg/minute and increased 2.5–5.0 mcg every few minutes until required response occurs | Selected patients with ACS: During the first 24 to 48 hours, those with heart failure (unless hypotension is present), large anterior myocardial infarction, persistent angina, or hypertension (BP is reduced by 10–20 mm Hg but not to < 80–90 mm Hg systolic) For longer use, patients with recurrent angina or persistent pulmonary congestion |
Nitrates: Long acting | ||
Isosorbide dinitrate | 10–20 mg orally 3 times a day; can be increased to 40 mg 3 times a day | Patients who have unstable angina or persistent severe angina and continue to have anginal symptoms after the beta-blocker dose is maximized A nitrate-free period of about 8–10 hours (typically at night) recommended to avoid tolerance (specific drugs recommend different durations of nitrate-free period) |
Isosorbide dinitrate (sustained-release) | 40–80 mg orally twice a day (typically given at 8 AM and 2 PM) | |
Isosorbide mononitrate | 20 mg orally twice a day, with 7 hours between 1st and 2nd doses | |
Isosorbide mononitrate (sustained-release) | 30 or 60 mg orally once a day, increased to 120 mg or, rarely, 240 mg | |
Nitroglycerin patches | 0.2–0.8 mg/hour applied between 6:00 and 9:00 AM and removed 12–14 hours later to avoid tolerance | |
Nitroglycerin ointment 2% preparation (15 mg/2.5 cm) | 1.25 cm spread evenly over upper torso or arms every 6 to 8 hours and covered with plastic, increased to 7.5 cm as tolerated, and removed for 8–12 hours each day to avoid tolerance | |
Opioids | ||
Morphine | 2–4 mg IV, repeated as needed | Morphine should be used judiciously (eg, if nitroglycerin is contraindicated or if patient has symptoms despite maximal doses of nitroglycerin) given a possible increase in mortality as well as attenuation of P2Y12 receptor inhibitor activity |
PCSK-9 inhibitors | ||
Alirocumab | Initial dose: 75 mg subcutaneously, once every 2 weeks or 300 mg subcutaneously once every 4 weeks | For patients not at target LDL-C levels, used alone or in combination with other lipid-lowering therapies (eg, statins, ezetimibe) for the treatment of adults with primary hyperlipidemia (including familial hypercholesterolemia) |
Evolocumab | Initial dose for primary hyperlipidemia: 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously once monthly | For patients not at target LDL-C levels, used alone or in combination with other lipid-lowering therapies (eg, statins, ezetimibe) for the treatment of adults with primary hyperlipidemia (including familial hypercholesterolemia) |
Statins (HMG-CoA reductase inhibitors) | ||
Atorvastatin Fluvastatin Lovastatin Pravastatin Rosuvastatin Simvastatin | Variable† (see Dyslipidemia) | Patients with CAD should be given maximally tolerated statin dose |
Other medications | ||
Ivabradine | 5 mg orally twice a day, increased to 7.5 mg orally twice a day if needed | Inhibits sinus node For symptomatic treatment of chronic stable angina pectoris in patients with normal sinus rhythm who cannot take beta-blockers In combination with beta-blockers in patients inadequately controlled by beta-blocker alone and whose heart rate > 60 beats/minute |
Ranolazine | 500 mg orally twice a day, increased to 1000 mg orally twice a day as needed | Patients in whom anginal symptoms continue despite treatment with other antianginal drugs |
* Clinicians may use different combinations of medications depending on the type of coronary artery disease that is present. | ||
† Refer to the manufacturer's prescribing information or a drug information database for specific dosing information. | ||
‡ Lower doses of Direct-acting oral anticoagulants are sometimes used, based on patient-specific risk factors. | ||
§ Higher doses of aspirin do not provide greater protection and increase risk of adverse effects. | ||
¶ Of low molecular weight heparins (LMWHs), enoxaparin is preferred. | ||
ACS = acute coronary syndromes; BP = blood pressure; CABG = coronary artery bypass grafting; CAD = coronary artery disease; HMG = hydroxymethylglutaryl; INR = international normalized ratio; LDL-C = low-density lipoprotein cholesterol; LV = left ventricular; MI = myocardial infarction; NSTEMI = non–ST-segment elevation MI; PCI = percutaneous intervention; STEMI = ST-segment elevation MI. | ||
General references
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
2. Ibrahim K, Shah R, Goli RR, et al. Fentanyl Delays the Platelet Inhibition Effects of Oral Ticagrelor: Full Report of the PACIFY Randomized Clinical Trial. Thromb Haemost. 2018;118(8):1409-1418. doi:10.1055/s-0038-1666862
3. Kubica J, Adamski P, Ostrowska M, et al. Morphine delays and attenuates ticagrelor exposure and action in patients with myocardial infarction: the randomized, double-blind, placebo-controlled IMPRESSION trial. Eur Heart J. 2016;37(3):245-252. doi: 10.1093/eurheartj/ehv547
4. Meine TJ, Roe MT, Chen AY, et al. Association of intravenous morphine use and outcomes in acute coronary syndromes: results from the CRUSADE Quality Improvement Initiative. Am Heart J. 2005;149(6):1043-1049. doi 10.1016/j.ahj.2005.02.010
Antiplatelet Agents
Aspirin, clopidogrel, prasugrel, ticagrelor, and glycoprotein (GP) IIb/IIIa inhibitors are examples of antiplatelet agents. In general, the goal with dosage and duration of antiplatelet agent use is to balance the decreased risk of coronary thrombosis with the increased risk of bleeding.
All patients are given aspirin 160 to 325 mg (not enteric-coated), if not contraindicated (eg, life-threatening active bleeding). Chewing the first dose before swallowing quickens absorption. Aspirin reduces short- and long-term mortality risk (1).
If aspirin cannot be taken initially, clopidogrel 75 mg orally once a day or ticlopidine 250 mg orally twice a day may be used. Clopidogrel has largely replaced ticlopidine for routine use because of the risk of neutropenia with ticlopidine.
Patients not undergoing revascularization
Patients with acute coronary syndrome (ACS) in whom intervention is not possible or recommended are treated with dual antiplatelet therapy with aspirin and a P2Y12 inhibitor (ticagrelor, prasugrel, or clopidogrel) for at least 12 months before transitioning to aspirin monotherapy. A proton pump inhibitor should be given with dual antiplatelet therapy.
Patients undergoing revascularization
In patients undergoing PCI, a loading dose of clopidogrel (300 to 600 mg orally once), prasugrel (60 mg orally once), or ticagrelor (180 mg orally once) improves outcomes (1). For urgent PCI, prasugrel and ticagrelor are more rapid in onset and may be preferred. IV cangrelor may also be used during PCI to reduce ischemic events in patients who are P2Y12-inhibitor naive.
Some clinicians give a GP IIb/IIIa inhibitor during (or sometimes before) PCI for patients with high-risk lesions (high thrombus burden, inadequate perfusion despite relief of obstruction ["no reflow"]) (2). The GP IIb/IIIa inhibitor is continued for 6 to 24 hours, and angiography is performed before the infusion period is over. GP IIb/IIIa inhibitors are not recommended for patients receiving fibrinolytics. Abciximab, tirofiban, and eptifibatide appear to have equivalent efficacy, and the choice of agent should depend on other factors (eg, cost, availability, familiarity).
After PCI, patients may receive dual antiplatelet therapy as for patients who are not undergoing revascularization. However, if bleeding risk is a concern, patients can be transitioned to monotherapy with aspirin or a P2Y12 inhibitor after 1 month, or de-escalated from ticagrelor or prasugrel to clopidogrel, which has a lower bleeding risk, as part of ongoing dual antiplatelet therapy. Thereafter,the use of P2Y12 inhibitors as an option for long term antiplatelet monotherapy after the discontinuation of dual antiplatelet therapy represents a change from the historical practice of using long-term low-dose aspirin.
Patients requiring long-term anticoagulation (eg, patients with atrial fibrillation) who are on "triple" therapy (dual antiplatelet plus an anticoagulant) after PCI can be transitioned to clopidogrel antiplatelet monotherapy along with their oral anticoagulant after 1 to 4 weeks.
Antiplatelet agent references
1. Lawton JS, Tamis-Holland JE, Bangalore S, et al. 2021 ACC/AHA/SCAI guideline for coronary artery revascularization: a report of the ACC/AHA Joint Committee on Clinical Practice Guidelines. J Am Coll Cardiol. 2022;79(2):e21-e129. doi: 10.1016/j.jacc.2021.09.006
2. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
Anticoagulants
Either a low molecular weight heparin (LMWH), unfractionated heparin, or bivalirudin is given routinely to patients with acute coronary syndrome unless contraindicated (eg, by active bleeding or planned use of streptokinase or anistreplase) (1).
Choice of agent depends on whether revascularization is anticipated, as well as other factors such as patient characteristics, cost, and local practice. The LMWHs have better bioavailability, are given by simple weight-based dose without monitoring activated partial thromboplastin time (aPTT) and dose titration, and have lower risk of heparin-induced thrombocytopenia; they are recommended when an early invasive strategy is not planned. Bivalirudin is recommended for patients with a known or suspected history of heparin-induced thrombocytopenia who are undergoing PCI. Anticoagulants are continued for:
Duration of PCI in patients undergoing this procedure
Duration of hospital stay (in patients on LMWH) or 48 hours (in patients on unfractionated heparin) in all other cases
Patients at high risk of systemic emboli (eg, atrial fibrillation with CHA2DS2VASc score ≥ 2) also require long-term therapy with an oral anticoagulant (eg, warfarin, dabigatran, apixaban, rivaroxaban). Conversion to oral anticoagulants should begin 48 hours after symptom resolution or PCI.
Unfractionated heparin
Unfractionated heparin is a recommended therapy for use in patients with non-ST-segment elevation acute coronary syndrome (NSTE-ACS), and in patients with any ACS undergoing PCI (1).
Unfractionated heparin is more complicated to use because it requires frequent (every 6 hours) dosing adjustments to achieve an aPTT 1.5 to 2 times the control value. In patients undergoing angiography, further dosing adjustment is made to achieve an activated clotting time (ACT) of 200 to 250 seconds if the patient is treated with a GP IIb/IIIa inhibitor and 250 to 300 seconds if a GP IIb/IIIa inhibitor is not being given. However, if bleeding develops after catheterization, the effects of unfractionated heparin are shorter and can be reversed (by promptly stopping the heparin infusion and giving protamine sulfate).
Low molecular weight heparin
Enoxaparin is a recommended alternative to unfractionated heparin therapy in patients with NSTE-ACS in whom an early invasive strategy is not planned, and IV enoxaparin may be considered as an alternative therapy to unfractionated heparin or bivalirudin in patients with ACS undergoing PCI (1). Enoxaparin is also the recommended therapy for patients undergoing fibrinolysis.
The LMWHs have better bioavailability, are given by simple weight-based dosing without monitoring aPTT and dose titration, and have lower risk of heparin-induced thrombocytopenia. They also may produce an incremental benefit in outcomes relative to unfractionated heparin in patients with ACS. Of the LMWHs, enoxaparin is the recommended agent (1). However, enoxaparin dosing is adjusted in patients > 75 years old with STEMI due to a higher bleeding risk (2), and its effects are not completely reversible with protamine.
Heparin alternatives
The direct thrombin inhibitor bivalirudin has a lower incidence of serious bleeding and improved outcomes compared to heparin (1). Bivalirudin is an acceptable alternative to unfractionated heparin for patients undergoing PCI who are at high risk of bleeding.
The factor Xa inhibitor fondaparinux is a recommended alternative therapy to unfractionated heparin in patients with NSTE-ACS in whom an early invasive strategy is not planned and is a recommended alternative therapy to enoxaparin in patients undergoing fibrinolytic therapy. Fondaparinux is not recommended in patients undergoing PCI; it has been shown to cause a higher rate of complications without benefit over unfractionated heparin in patients with STEMI undergoing PCI (3).
Oral anticoagulants
For patients who require anticoagulation for another reason (eg, atrial fibrillation), direct-acting oral anticoagulants (apixaban, dabigatran, edoxaban, rivaroxaban) are preferred long term over warfarin, unless there is a contraindication to them (1). For most patients requiring anticoagulation, triple therapy with oral anticoagulation, a P2Y12 inhibitor, and aspirin is continued up to 1 week to 1 month after intervention, and then patients are continued on oral anticoagulation and a P2Y12 inhibitor for 6 months to 1 year. Calcium channel blockers and nitrates may also be given to reduce risk of coronary spasm.
Anticoagulants references
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
2. National Library of Medicine. DailyMed. Label: ENOXAPARIN SODIUM injection. September 30, 2025. Accessed April 1, 2026.
3. Yusuf S, Mehta SR, Chrolavicius S, et al. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA. 2006;295(13):1519-1530. doi:10.1001/jama.295.13.joc60038
Beta-Blockers
Beta-blockers are recommended unless contraindicated (eg, by bradycardia, heart block, hypotension, or asthma), especially for high-risk patients. Beta-blockers reduce heart rate, arterial pressure, and contractility, thereby reducing cardiac workload and oxygen demand. Infarct size largely determines cardiac performance after recovery. Oral beta-blockers given within the first few hours improve prognosis by reducing infarct size, recurrence rate, incidence of ventricular fibrillation, and mortality risk (1), but they have limited benefit and are not routinely used in patients with preserved left ventricular ejection fraction (2, 3, 4).
Heart rate and BP must be carefully monitored during treatment with beta-blockers. Dosage is reduced if bradycardia or hypotension develops. Excessive adverse effects may be reversed by infusion of the beta-adrenergic agonist isoproterenol 1 to 5 mcg/minute.
Beta-blocker references
1. Chen ZM, Pan HC, Chen YP, et al. Early intravenous then oral metoprolol in 45,852 patients with acute myocardial infarction: randomised placebo controlled trial. Lancet. 2005;366(9497):1622-1632. doi: 10.1016/S0140-6736(05)67661-1
2. Ibanez B, Latini R, Rossello X, et al. Beta-Blockers after Myocardial Infarction without Reduced Ejection Fraction. N Engl J Med. 2025;393(19):1889-1900. doi:10.1056/NEJMoa2504735
3. Munkhaugen J, Kristensen AMD, Halvorsen S, et al. Beta-Blockers after Myocardial Infarction in Patients without Heart Failure. N Engl J Med. 2025;393(19):1901-1911. doi:10.1056/NEJMoa2505985
4. Yndigegn T, Lindahl B, Mars K, et al. Beta-Blockers after Myocardial Infarction and Preserved Ejection Fraction. N Engl J Med. 2024;390(15):1372-1381. doi:10.1056/NEJMoa2401479
Nitrates
A short-acting nitrate, nitroglycerin, is used to reduce pain and cardiac workload in selected patients. Nitroglycerin dilates veins, arteries, and arterioles, reducing left ventricular preload and afterload. As a result, myocardial oxygen demand is reduced, lessening ischemia.
Chest pain can be treated with sublingual or intravenous nitroglycerin, or sometimes morphine or fentanyl. Nitroglycerin is preferable to opioids (1), which should be used judiciously (eg, if a patient has a contraindication to nitroglycerin or is in pain despite maximal nitroglycerin therapy). Nitroglycerin is initially given sublingually, followed by continuous IV drip if needed for pain, hypertension, or pulmonary edema. Nitroglycerin in either form should not be used if the systolic blood pressure is below 90 mm Hg or if the decrease in systolic blood pressure is > 30 mm Hg from baseline.
Nitroglycerin has been used historically with the intent of reducing infarct size and improve outcomes, but large trials found no evidence of benefit and this practice is no longer recommended (2, 3).
Nitrates references
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
2. GISSI-3. Effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'infarto Miocardico. Lancet. 1994;343(8906):1115-1122.
3. ISIS-4. A randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group. Lancet. 1995;345(8951):669-685.
Fibrinolytics
Tenecteplase (TNK), alteplase (rTPA), reteplase (rPA), and streptokinase, all given IV, are plasminogen activators. They convert single-chain plasminogen to double-chain plasminogen, which has fibrinolytic activity. They have different characteristics and dosing regimens (see table ) and are appropriate only for selected patients with STEMI.
Tenecteplase and reteplase are recommended most often because of their simplicity of administration; tenecteplase is given as a single bolus over 5 seconds and reteplase as a double bolus 30 minutes apart; alteplase is given as an infusion over 90 minutes (1). Tenecteplase, reteplase, and alteplase are preferred over other fibrinolytics. Reteplase appears to have higher recanalization rates than alteplase with no difference in bleeding (2).; Tenecteplase has been shown to be noninferior, and possibly superior when combined with ticagrelor to alteplase in terms of recanalization (3, 4).
Streptokinase (not available in the United States) may induce allergic reactions, especially if it has been used previously, and must be given by infusion over 30 to 60 minutes; however, it has a low incidence of intracerebral hemorrhage and is relatively inexpensive. Anistreplase, related to streptokinase, is similarly allergenic and slightly more expensive but can be given as a single bolus. Recanalization rate is lower than that with other plasminogen activators. Because of the possibility of allergic reactions, patients who previously received streptokinase or anistreplase are not given that medication again.
IV Fibrinolytic Therapies
Medication | Circulating half-life (minutes) | Concurrent heparin | Allergic reactions |
|---|---|---|---|
Alteplase | 6 | Yes | Rare |
Reteplase | 13–16 | Yes | Rare |
Streptokinase (not available in the United States) | 20 | No | Yes |
Tenecteplase | Initial half-life of 20–24 minutes; terminal phase half-life of 90–130 minutes | Yes | Rare |
Contraindications to fibrinolytic therapy
There are many absolute and relative contraindications to fibrinolytic therapy. In general, the presence of active bleeding or a condition where bleeding would be life-threatening is an absolute contraindication (see Table ).
Fibrinolytics references
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
2. Bode C, Smalling RW, Berg G, et al. Randomized comparison of coronary thrombolysis achieved with double-bolus reteplase (recombinant plasminogen activator) and front-loaded, accelerated alteplase (recombinant tissue plasminogen activator) in patients with acute myocardial infarction. The RAPID II Investigators. Circulation. 1996;94(5):891-898. doi:10.1161/01.cir.94.5.891
3. Günlü S, Demir M. Comparison of tenecteplase versus alteplase in STEMI patients treated with ticagrelor: A cross-sectional study. Am J Emerg Med. 2022;58:52-56. doi:10.1016/j.ajem.2022.05.021
4. Zhao X, Zhu Y, Zhang Z, et al. Tenecteplase versus alteplase in treatment of acute ST-segment elevation myocardial infarction: A randomized non-inferiority trial. Chin Med J (Engl). 2024;137(3):312-319. doi:10.1097/CM9.0000000000002731
Other Medications for Post-acute Treatment of Acute Coronary Syndrome
Angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) reduce mortality risk in patients with myocardial infarction, especially in those with anterior infarction, left ventricular ejection fraction ≤ 40%, hypertension, or diabetes (1). The greatest benefit occurs in the patients at highest risk early during convalescence. ACE inhibitors and ARBs are given > 24 hours after thrombolysis stabilization and, because of continued beneficial effect, may be prescribed long-term. They provide long-term cardioprotection by improving endothelial function (2), particularly in patients with heart failure, hypertension, diabetes, or chronic kidney disease (3). Contraindications include hypotension, kidney failure, bilateral renal artery stenosis, and known allergy.
Mineralocorticoid receptor antagonists (spironolactone or eplerenone) are indicated to reduce morbidity and mortality in patients with left ventricular dysfunction and either heart failure symptoms or diabetes following ACS (1).
In patients with heart failure, data also support the use of sodium–glucose co-transporter 2 (SGLT2) inhibitors after MI, regardless of diabetes status, to reduce the risk of worsening heart failure, cardiovascular mortality, or both (1, 3).
Statins (HMG-CoA reductase inhibitors) have long been used for prevention of coronary artery disease and acute coronary syndromes, but there is evidence that they also have short-term benefits, such as stabilizing plaque, reversing endothelial dysfunction, decreasing thrombogenicity, and reducing inflammation. Thus, all patients without contraindications (eg, statin-induced myopathy, liver dysfunction) to therapy should receive a statin at the maximally tolerated dose as early as possible following ACS regardless of their serum lipid levels (1, 4).
PCSK-9 inhibitors (evolocumab, alirocumab), the cholesterol absorption inhibitor ezetimibe, and bempedoic acid are used for patients not at target low-density lipoprotein cholesterol levels on maximal statin therapy alone or for those who cannot tolerate a statin (1, 5).
In patients who have had an MI, icosapent ethyl is used in patients with hypertriglyceridemia to reduce risk of subsequent ischemic events and cardiovascular death (6).
Long-term colchicine appears to improve outcomes in patients with chronic coronary disease, after MI, and possibly after ACS in general. (1, 7).
Other medications references
1. Rao SV, O'Donoghue ML, Ruel M, et al. 2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. 2025;151(13):e771-e862. doi:10.1161/CIR.0000000000001309
2. Heart Outcomes Prevention Evaluation Study Investigators, Yusuf S, Sleight P, et al. Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. N Engl J Med. 2000;342(3):145-153. doi:10.1056/NEJM200001203420301
3. Byrne RA, Rossello X, Coughlan JJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44(38):3720-3826. doi:10.1093/eurheartj/ehad191
4. Wang WT, Hellkamp A, Doll JA, et al. Lipid Testing and Statin Dosing After Acute Myocardial Infarction. J Am Heart Assoc. 2018;7(3):e006460. doi:10.1161/JAHA.117.006460
5. Writing Committee Members, Blumenthal RS, Morris PB, et al. 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia: A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines. Circulation. Published online March 13, 2026. doi:10.1161/CIR.0000000000001423
6. Gaba P, Bhatt DL, Steg PG, et al. Prevention of Cardiovascular Events and Mortality With Icosapent Ethyl in Patients With Prior Myocardial Infarction. J Am Coll Cardiol. 2022;79(17):1660-1671. doi:10.1016/j.jacc.2022.02.035
7. Nidorf SM, Fiolet ATL, Mosterd A, et al. Colchicine in Patients with Chronic Coronary Disease. N Engl J Med. 2020;383(19):1838-1847. doi:10.1056/NEJMoa2021372
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