Treatment - STEMI Medical Therapy

Medical Therapy

Initial medical management of STEMI consists of relief of ischemic pain with nitrates and morphine, antithrombotic measures including antiplatelet agents (aspirin, thienopyridines and glycoprotein IIb/IIIa inhibitors), and systemic anticoagulation (heparin or bivalirudin) and beta-adrenergic blockade.

Supplemental oxygen should be administered if arterial desaturation is present, but not as a routine measure. [Jernberg 2018;1a] Medical therapy initiated before hospital discharge may include angiotensin converting enzyme inhibitors, angiotensin receptor blockers, sacubitril/valsartan (Entresto, Novartis), continued beta-adrenergic blockade, aldosterone antagonists and HMG-CoA reductase inhibitors.

Antithrombotic Management

Aspirin

Early antithrombotic administration at the time of STEMI diagnosis consists of non-enteric-coated aspirin 162 mg to 325 mg (unless contraindicated) p.o., chewed immediately. Lifelong therapy using 81 mg to 325 mg daily should follow.
Anticoagulation

Initial systemic anticoagulation should be started in all patients with STEMI unless a contraindication exists. Unfractionated heparin, low-molecular-weight heparin (enoxaparin or fondaparinux) or bivalirudin may be used; unfractionated heparin should be given for 48 hours total and low molecular weight heparin until hospital discharge or for 8 days.

P2Y12 inhibitors

P2Y12 receptor antagonists (clopidogrel, prasugrel, ticagrelor (Brilinta, AstraZeneca) and ticlopidine) are indicated in all STEMI cases unless urgent surgery is required. Clopidogrel can also be used as an adjunct to fibrinolytic therapy in aspirin-intolerant patients. If urgent CABG is required, these agents should not be used; these agents should be discontinued for 5 to 7 days prior to CABG, unless the benefits of surgery outweigh the risk of bleeding.

For STEMI patients who have undergone PCI with coronary stenting, it is recommended that P2Y12 inhibitors be continued for 12 months, if possible, regardless of the type of stent used. Prasugrel is not recommended in patients with a history of stroke or transient ischemic attack (TIA). Ticlopidine is now used rarely due to risk of thrombocytopenia and thrombotic thrombocytopenic purpura (TTP).

Glycoprotein IIb/IIIa Inhibitors

These drugs include abciximab, eptifibatide and tirofiban. Glycoprotein IIb/IIIa inhibitors very strongly inhibit platelet function by blocking fibrinogen binding to the activated glycoprotein IIb/IIIa receptor complex. Any of these agents may be used in addition to aspirin, a P2Y12 inhibitor and anticoagulation (except with bivalirudin) at the time of PCI in high-risk patients with STEMI. There are no strong data to support the use of glycoprotein IIb/IIIa inhibitors prior to PCI at the present time.

Nitrates

Nitrates may be useful in the management of post-MI anginal symptoms, hypertension and HF; however, no clinical data exist documenting a mortality benefit. The use of nitrates should not preclude using the neurohormonal blocking agents that have mortality benefits.

Sublingual nitroglycerine tablets administered every 5 minutes, with a maximum dose of three tablets, can be given to relieve angina; should angina persist, intravenous nitroglycerine can be considered. Systemic hypotension and/or suspected right ventricular infarction are contraindications to the use of nitrates.

Phosphodiesterase-5 inhibitors (sildenafil, vardenafil, tadalafil) enhance nitric oxide production and can cause potentially fatal hypotension when used in combination with nitrates. Nitrates should not be used together with PDE-5 inhibitors within 24 hours (sildenafil) or 48 hours (vardenafil, tadalafil) due to this interaction.

Morphine

Morphine effectively relieves anginal chest pain and reduces the sensation of dyspnea when pulmonary edema is present. Morphine may cause respiratory depression and hypotension.

Beta-blockers

Although there are few data regarding the efficacy of beta-blockers during unstable angina and non-STEMI, there is an abundance of data supporting beta-adrenergic blockade with STEMI. ACC/AHA guidelines recommend early intravenous beta-blockers when no contraindication exists. Otherwise, oral administration of beta-blocker therapy may be initiated in the acute setting. Beta-blockade is contraindicated in cardiogenic shock, with systemic hypotension or with acute left heart decompensation. Long-term (lifetime) beta-blocker use reduces the incidence of recurrent MI and reduces post-MI mortality rates.

Angiotensin Converting Enzyme Inhibitors/Angiotensin Receptor Blockers

The ACC/AHA guidelines state that angiotensin converting enzyme (ACE) inhibitors are reasonable (class IIa recommendation) for all patients with STEMI and no contraindications. Importantly, in patients with impaired LV systolic function or diabetes, ACE inhibitors have a class I indication. Angiotensin receptor blockers (ARB) are the recommended alternative agents if the post-MI patient cannot tolerate ACE inhibitors due to cough.

Aldosterone Antagonists

In the EPHESUS (Epleronone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival) trial, the aldosterone antagonist eplerenone added to an ACE inhibitor was associated with lower mortality after an MI. This led to the recommendation for use of aldosterone antagonists with an ACE inhibitor and beta-blocker in patients with STEMI with LV systolic dysfunction (EF < 40%) and either diabetes or symptomatic HF (and no contraindication, ie, serum creatinine > 2.5 mL/min and/or potassium > 5.0 mEq/L). Some clinicians prescribe spironolactone instead of eplerenone due to cost concerns; however, there are no head-to-head trial data to support this practice.

HMG-CoA Reductase Inhibitors

Every STEMI patient (without contraindications) should receive a statin; see HMG-CoA Reductase Inhibitor Topic Review. The 2018 American College of Cardiology/American Heart Association cholesterol guidelines recommend (class I) high-intensity statin therapy (defined as a regimen to achieve LDL reduction ≥ 50%) in patients aged younger than 75 years. For age older than 75 years, high- or moderate-intensity statin therapy (defined as 30-49% LDL reduction) should be initiated (class IIa recommendation) depending on individual risk factors and preferences. No specific target LDL level is recommended in the guidelines — only a reduction of LDL levels from baseline. [Grundy 2018;10a;11a(e294, e295)] The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) trial and Pravastatin or Atorvastatin Evaluation and Infection Therapy–Thrombolysis in Myocardial Infarction 22 (PROVE-IT TIMI 22) trial used atorvastatin (80 mg/day given orally) with good results. Statin therapy should be lifelong after an acute coronary syndrome, unless a contraindication exists or the baseline LDL cholesterol is below 70 mg/dL.

Calcium Channel Blockers

The non-dihydropyridine calcium channel blockers diltiazem and verapamil can be used for symptomatic management of angina when there is a contraindication to beta-blockers, such as in asthma, and no HF or significant LV systolic dysfunction are present. However, an analysis of 28 trials showed no beneficial effect of calcium channel blockers on infarct size or the rate of reinfarction with STEMI. [O’Gara 2013;29a(e106)] Sublingual nifedipine, which is sometimes used in hypertensive emergencies, is contraindicated in patients with CAD due to a reflex increase in sympathetic nervous system activity, which can be harmful.

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