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, coronary artery bypass grafting, or fibrinolytic therapy) and pharmacologic therapy to treat ACS and underlying coronary artery disease.
Medications used depend on the type of ACS and include
clopidogrel if fibrinolytic therapy has not been given)
Beta-blocker
Glycoprotein IIb/IIIa inhibitor for certain patients undergoing percutaneous coronary intervention (PCI) and high-risk lesions (eg, high thrombus burden, no reflow)
heparinST-segment elevation myocardial infarction [STEMI] who are at high risk of bleeding)
Fibrinolytics for select patients with STEMI when timely PCI unavailable
Angiotensin-converting enzyme (ACE) inhibitor (as early as possible)
Statins
Medications for Coronary Artery Disease).
Fibrinolyticsshould be used if not contraindicated for STEMI if primary PCI is not immediately available but worsen outcome for unstable angina and non-ST elevation myocardial infarction (NSTEMI).
Nitroglycerin is preferable to morphine, which should be used judiciously (eg, if a patient has a contraindication to nitroglycerin or is in pain despite nitroglycerin therapy). is initially given sublingually, followed by continuous IV drip if needed. Morphine 2 to 4 mg IV, repeated every 15 minutes as needed, is highly effective but can depress respiration, can reduce myocardial contractility, and is a potent venous vasodilator. Evidence also suggests that morphine interferes with some P2Y12 receptor inhibitors. A large retrospective trial showed that morphine may increase mortality in patients with acute myocardial infarction (1, 2). Hypotension and bradycardia secondary to morphine can usually be overcome by prompt elevation of the lower extremities.
shock are ominous and must be treated aggressively with IV fluids and sometimes vasopressors.
Medications for Coronary Artery Disease*
Medication | Dosage | Use |
|---|---|---|
Angiotensin-converting enzyme (ACE) inhibitors | ||
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) | ||
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‡ | ||
5 mg orally twice a day | May be useful long-term in patients with non-valvular atrial fibrillation | |
150 mg orally twice a day (or 110–150 mg orally twice a day for patients also taking P2Y12 inhibitors) | ||
60 mg orally once a day | ||
20 mg orally once a day (or 15 mg orally once a day for patients also taking P2Y12 inhibitors) | ||
Anticoagulants: Direct thrombin inhibitors | ||
350 mcg/kg (IV bolus) followed by 25 mcg/kg/minute (IV infusion) | ||
Variable† | ||
Anticoagulants: Factor Xa inhibitor | ||
2.5 mg subcutaneously every 24 hours | ||
Anticoagulants: Low molecular weight heparins | ||
Tinzaparin | Variable† | Patients with unstable angina or NSTEMI Patients < 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 | ||
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 | 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 | ||
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 | ||
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 | |
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) | |
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 | |
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 | ||
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. | |
Variable† | ||
Variable† | ||
Variable† | ||
Calcium channel blockers | ||
Variable† | Patients with stable angina if symptoms persist despite nitrates use or if nitrates are not tolerated | |
Variable† | ||
Variable† | ||
Variable† | ||
Variable† | ||
Glycoprotein IIb/IIIa inhibitors | ||
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 | |
Variable† | ||
Variable† | ||
Nitrates: Short acting | ||
0.3–0.6 mg every 4–5 minutes up to 3 doses | All patients for immediate relief of chest pain; used as needed | |
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 | ||
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) | |
40–80 mg orally twice a day (typically given at 8 AM and 2 PM) | ||
20 mg orally twice a day, with 7 hours between 1st and 2nd doses | ||
30 or 60 mg orally once a day, increased to 120 mg or, rarely, 240 mg | ||
0.2–0.8 mg/hour applied between 6:00 and 9:00 AM and removed 12–14 hours later to avoid tolerance | ||
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 | ||
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 | ||
Initial dose: 75 mg subcutaneously, once every 2 weeks or 300 mg subcutaneously once every 4 weeks | ||
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) | ||
Variable† (see Dyslipidemia) | Patients with CAD should be given maximally tolerated statin dose | |
Other medications | ||
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 | |
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 | ||
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. | ||
References
1. 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 149(6):1043-1049, 2005. doi 10.1016/j.ahj.2005.02.010
2. 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 37(3):245–252, 2016. doi: 10.1093/eurheartj/ehv547
Antiplatelet Agents
aspirin 160 to 325 mg (not enteric-coated), if not contraindicated (eg, life-threatening active bleeding), at presentation and 81 mg once a day indefinitely thereafter. Chewing the first dose before swallowing quickens absorption. Aspirin reduces short- and long-term mortality risk (1).
If aspirinClopidogrel has largely replaced ticlopidine for routine use because neutropenia is a risk with ticlopidine, and the white blood cell count must be monitored regularly if patients are taking ticlopidine.
Patients not undergoing revascularization
Patients with acute coronary syndrome
Patients undergoing revascularization
Antiplatelet agent reference
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 79(2):e21–e129, 2022. doi: 10.1016/j.jacc.2021.09.006
Anticoagulant Agents
Either a low molecular weight heparin (LMWH), unfractionated heparin
Patients at high risk of systemic emboli (eg, atrial fibrillation with CHA2DS2VASc score
Unfractionated heparin
heparin are shorter and can be reversed (by promptly stopping the heparin
Low molecular weight heparin
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 heparinenoxaparin may pose a higher bleeding risk in patients with STEMI who are >
Choice of heparin
heparin in patients with unstable angina or NSTEMI and in patients < age 75 years with STEMI who are not undergoing PCI.
< 30 mL/minute (0.5 mL/second).
heparin is continued for 48 hours (or longer if symptoms persist).
Heparin alternatives
The difficulties with the heparins (including bleeding complications, the possibility of , and, with unfractionated heparin, the need for dosing adjustments) have led to the search for alternative anticoagulants.
The direct thrombinthrombinheparin for patients undergoing PCI who are at high risk of bleeding. The factor Xaheparin in patients with STEMI (1). Although routine use of these alternative anticoagulants is thus not currently recommended, they should be used in place of unfractionated heparin or LMWH in patients with a known or suspected history of heparin-induced thrombocytopenia.
For patients who require anticoagulation for another reason (eg, atrial fibrillation
Anticoagulants reference
1. 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).
Beta-blocker reference
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 366:1622–1632, 2005.
Nitrates
Nitroglycerin dilates veins, arteries, and arterioles, reducing left ventricular preload and afterload. As a result, myocardial oxygen demand is reduced, lessening ischemia.
heart failure, large anterior myocardial infarction, persistent chest discomfort, or hypertension. BP should not be reduced to < 110 to 120 mm Hg systolic; patients who remain symptomatic at that BP should have emergency PCI rather than further BP reduction.
Nitroglycerin is not routinely given to low-risk patients with uncomplicated myocardial infarction.
Fibrinolytics
plasminogen activator complex—APSAC), 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 IV Fibrinolytic Therapies) and are appropriate only for selected patients with STEMI).
tenecteplaseTenecteplaseReteplase has the highest risk of intracranial hemorrhage and a recanalization rate similar to that of tenecteplase, and it is expensive.
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 streptokinaseplasminogen activators. Because of the possibility of allergic reactions, patients who previously received streptokinase or anistreplase are not given that drug again.
Alteplase
IV Fibrinolytic Therapies
Medication | Circulating half-life (minutes) | Concurrent heparin | Allergic reactions |
|---|---|---|---|
Anistreplase | 100 | No | Yes |
6 | Yes | Rare | |
13–16 | Yes | Rare | |
Streptokinase (not available in the United States) | 20 | No | Yes |
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. The contraindications to fibrinolytic therapy are listed in the table Contraindications to Fibrinolytic Therapy.
Contraindications to Fibrinolytic Therapy
Absolute contraindications | Aortic dissection |
Previous hemorrhagic stroke (at any time) | |
Previous ischemic stroke within 1 year | |
Active internal bleeding (not menses) | |
Intracranial tumor | |
Pericarditis | |
Relative contraindications | Blood pressure > 180/110 mm Hg after initial antihypertensive therapy |
Trauma or major surgery within 4 weeks | |
Active peptic ulcer | |
Pregnancy | |
Bleeding diathesis | |
Noncompressible vascular puncture | |
Current anticoagulation (INR > 2) |
Other Medications for Acute Coronary Syndromes
Angiotensin-converting enzyme (ACE) inhibitors reduce mortality risk in patients with myocardial infarction, especially in those with anterior infarction, heart failure, or tachycardia. The greatest benefit occurs in the highest-risk patients early during convalescence. ACE inhibitors are given > 24 hours after thrombolysis stabilization and, because of continued beneficial effect, may be prescribed long-term.
Angiotensin II receptor blockers (ARBs) may be an effective alternative for patients who cannot tolerate ACE inhibitors (eg, because of cough). They are not first-line treatment after myocardial infarction. Contraindications include hypotension, kidney failure, bilateral renal artery stenosis, and known allergy.
Statins (HMG-CoA reductase inhibitors) have long been used for prevention of coronary artery disease and acute coronary syndromes, but there is now increasing 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).
PCSK-9 inhibitors
2).
Other medications references
1. 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. Published 2018 Jan 25. doi:10.1161/JAHA.117.006460
2. 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
