ACS Treatment (MONA-GAP-BA)

When should MONA drugs be given for ACS?

ASAP as needed (give first)

When should morphine be used in ACS?

Only for patients with unacceptable chest discomfort despite other treatments

Why is morphine not routinely used in ACS?

It may diminish antiplatelet effects

What is the dose of morphine for ACS?

2-5 mg IV repeated q5-30 min prn

What are the major adverse effects to monitor with morphine in ACS?

Hypotension, bradycardia, nausea/vomiting, sedation, and respiratory depression

When should oxygen be administered in ACS?

When SaO₂ <90% or the patient has respiratory distress

How do nitrates help treat ACS?

They dilate coronary arteries, improve collateral blood flow, decrease preload and afterload (modestly), and reduce chest pain

How should sublingual nitroglycerin be dosed in ACS?

0.4 mg every 5 minutes for up to 3 doses

When is IV nitroglycerin considered in ACS?

If chest pain or symptoms persist after sublingual nitroglycerin

When should nitroglycerin NOT be used?

SBP <90 mmHg

HR <50 bpm

right ventricular infarction

recent PDE-5 inhibitor use

When is ASA given in ACS?

immediately

What aspirin dose should be given immediately in ACS?

162–325 mg of non-enteric-coated chewable aspirin (if no contraindications)

What is the maintenance aspirin dose after ACS?

75–100 mg daily indefinitely

What can be used if a patient is intolerant to aspirin for ACS treatment?

Clopidogrel or ticagrelor

When are GAP drugs given in ACS treatment?

after MONA drugs, determined by plan

Name the GP IIb/IIIa receptor antagonists for ACS

Abciximab, eptifibatide, tirofiban

How do anticoagulants benefit patients with ACS?

They inhibit clotting factors and reduce infarct size

Which anticoagulants are commonly used in ACS?

LMWHs (enoxaparin, dalteparin), UFH, and bivalirudin (preferred for STEMI)

Name the P2Y12 inhibitors used in ACS

Clopidogrel, prasugrel, ticagrelor

When are BA drugs given in ACS treatment?

within 24 hours as needed and continued outpatient

How do beta-blockers benefit patients with ACS?

Decrease BP, HR, and contractility; decrease ischemia, reinfarction, and arrhythmias; prevent cardiac remodeling; improve long-term survival

When should beta-blockers be started after ACS?

Within the first 24 hours unless contraindicated

Which beta-blockers are preferred in ACS?

Beta-1 selective agents without intrinsic sympathomimetic activity

Which beta-blockers are preferred in patients with HFrEF after ACS?

Bisoprolol, metoprolol succinate, or carvedilol

What are alternatives to oral BBs in ACS treatment?

IV BB or oral long acting non-DHP CCB (diltiazem or verapamil)

When should ACE inhibitors be started after ACS?

Within the first 24 hours unless contraindicated

Which patients should continue an ACE inhibitor indefinitely after ACS?

Patients with LVEF <40%, hypertension, diabetes, or stable CKD

What are the benefits of ACE inhibitors in ACS?

Block angiotensin II production, prevent cardiac remodeling, and decrease preload and afterload

What is the alternative to ACEi in ACS treatment?

ARBs

Why should IV ACE inhibitors be avoided during the first 24 hours after ACS?

Increased risk of hypotension

Which medications should be avoided during hospitalization for ACS and why?

NSAIDs (except aspirin)

They increase the risk of mortality, reinfarction, hypertension, cardiac rupture, renal insufficiency, and heart failure

Which calcium channel blocker should be avoided in the acute setting of ACS and why?

Immediate-release nifedipine, increased risk of mortality

How does aspirin inhibit platelet aggregation?

It irreversibly inhibits COX-1 and COX-2, decreasing thromboxane A₂ (TXA₂) production

What does thromboxane A₂ (TXA₂) do?

It promotes platelet aggregation

How do P2Y12 inhibitors inhibit platelet aggregation?

They bind the platelet ADP (P2Y12) receptor, preventing ADP-mediated activation of the GPIIb/IIIa receptor complex

How do GPIIb/IIIa receptor antagonists inhibit platelet aggregation?

They block the platelet GPIIb/IIIa receptor, preventing fibrinogen binding and platelet aggregation

How do PAR-1 antagonists inhibit platelet aggregation?

They bind the PAR-1 receptor, preventing thrombin-mediated platelet aggregation

Which drugs are P2Y12 inhibitors?

Clopidogrel, prasugrel, ticagrelor, cangrelor

Which P2Y12 inhibitors are thienopyridines?

Clopidogrel and prasugrel

1. Which P2Y12 inhibitor(s) are prodrugs?

2. Which P2Y12 inhibitor(s) is NOT a prodrug?

1. Clopidogrel and prasugrel

2. Ticagrelor

1. Which P2Y12 inhibitor(s) bind irreversibly to the P2Y12 receptor?

2. Which P2Y12 inhibitor binds reversibly to the P2Y12 receptor?

1. Clopidogrel and prasugrel

2. Ticagrelor

What is dual antiplatelet therapy (DAPT) for ACS?

Aspirin plus a P2Y12 inhibitor

When should a P2Y12 inhibitor loading dose be given?

Prior to PCI or at the time of ACS diagnosis if PCI is not being performed

What follows the loading dose of a P2Y12 inhibitor?

A maintenance dose

Which drug class blocks the final common pathway of platelet aggregation?

GPIIb/IIIa receptor antagonists

Which receptor does thrombin activate to promote platelet aggregation?

PAR-1

Clopidogrel:

1. what is the LD

2. what is the MD

3. exception

1. 300-600 mg po (if PCI then 600 mg)

2. 75 mg po daily

3. patients who are >75 years old who had fibrinolytic therapy for STEMI do NOT need a loading dose, start on maintenance dose

Which enzyme is responsible for metabolizing Clopidogrel to its active form?

CYP2C19

Clopidogrel:

1. contraindications

2. warnings

3. side effects

1. active serious bleed

2. bleed risk (stop 5 d before surg); dont use with omeprazole or esomeprazole, TTP

3. generally none, unless bleeding occurs

Which P2Y12 inhibitor is only indicated for ACS managed with PCI?

Prasugrel (Effient)

Prasugrel (effient)

1. LD

2. MD

3. exception

1. 60 mg po <1 hr after PCI

2. 10 mg po qd + ASA

3. MD of 5 mg qd if patient weighs <60 kg

How should prasugrel be stored?

Protect from moisture and dispense in the original container

What is the boxed warning for prasugrel?

Significant, sometimes fatal, bleeding

not rec for patients ≥75 years old unless they are high risk (diabetes or prior MI)

must stop 7 days before elective surgery

What are the contraindications to prasugrel?

Active serious bleeding and history of TIA or stroke

What are the warnings for prasugrel?

Bleeding risk, premature discontinuation (↑ thrombosis risk), and thrombotic thrombocytopenic purpura (TTP)

What is the major side effect of prasugrel?

Bleeding (higher risk than clopidogrel)

Ticagrelor (Brilinta):

1. LD

2. MD

1. 180 mg

2. 90 mg po BID x 1 year then 60 mg BID

How can ticagrelor tablets be administered if the patient cannot swallow them?

Crushed and mixed with water for oral or NG tube administration

What is the boxed warning for ticagrelor?

Significant, sometimes fatal, bleeding

What aspirin maintenance dose should NOT be exceeded with ticagrelor and why?

100 mg/day; Higher aspirin doses reduce ticagrelor effectiveness

When should ticagrelor be avoided before surgery?

If CABG is likely, stop at least 5 days before surgery

What are the contraindications to ticagrelor?

Active serious bleeding and history of intracranial hemorrhage

What are the warnings for ticagrelor?

Bleeding risk, severe hepatic impairment, bradyarrhythmias, premature discontinuation (↑ thrombosis risk), and TTP

What are the major side effects of ticagrelor?

Bleeding, dyspnea (>10%), increased serum creatinine, and increased uric acid

Which P2Y12 inhibitor is given intravenously?

Cangrelor

When is cangrelor indicated?

As an adjunct to PCI in P2Y12 inhibitor-naïve patients not receiving a GPIIb/IIIa inhibitor

What is the dosing regimen for cangrelor?

30 mcg/kg IV bolus before PCI, then 4 mcg/kg/min infusion for 2 hours or the duration of PCI (whichever is longer)

Canagrelor:

1. CI

2. SE

1. Significant active bleeding

2. bleeding

How long do cangrelor's effects last after discontinuation?

About 1 hour

What should patients receive after cangrelor is discontinued?

Transition to an oral P2Y12 inhibitor after PCI

What is the major drug interaction concern with P2Y12 inhibitors?

Additive bleeding risk with other medications

Which medications increase bleeding risk when combined with P2Y12 inhibitors?

NSAIDs, warfarin, SSRIs, and SNRIs

Should P2Y12 inhibitors be discontinued if bleeding occurs after ACS?

No, if possible manage bleeding without stopping the P2Y12 inhibitor because early discontinuation increases cardiovascular events

Which PPIs should be avoided with clopidogrel and why?

Omeprazole and esomeprazole; They inhibit CYP2C19 and decrease clopidogrel's antiplatelet effect

Which P2Y12 inhibitor is a major CYP3A4 substrate? and which drugs should be avoided when taking?

Ticagrelor; Strong CYP3A4 inhibitors and strong CYP3A4 inducers

Which statins should be limited to ≤40 mg/day with ticagrelor?

Simvastatin and lovastatin

Which medication should be monitored when starting or changing ticagrelor?

Digoxin

Which diabetes medication has increased effects with clopidogrel?

Repaglinide (Increased risk of hypoglycemia)

Which GPIIb/IIIa receptor antagonists reversibly block the GPIIb/IIIa receptor?

Eptifibatide and tirofiban

Which GPIIb/IIIa receptor antagonist irreversibly blocks the GPIIb/IIIa receptor?

Abciximab

When can eptifibatide and tirofiban be used for ACS treatment?

Medical management of ACS or patients receiving PCI ± stent

When is abciximab indicated for ACS treatment?

Only for PCI ± stent

What medication is given with a GPIIb/IIIa receptor antagonist during PCI?

Heparin

When is abciximab not recommended for ACS treatment?

Medical management of NSTE-ACS without PCI

What are the contraindications to GPIIb/IIIa receptor antagonists?

Thrombocytopenia, history of bleeding diathesis, active internal bleeding, severe uncontrolled hypertension, recent major surgery or trauma, and recent stroke or history of hemorrhagic stroke (eptifibatide)

What are the major side effects of GPIIb/IIIa receptor antagonists?

Bleeding and thrombocytopenia

What administration precaution should be followed with eptifibatide and tirofiban?

Do not shake the vials

When does platelet function return after stopping eptifibatide or tirofiban?

Approximately 4–8 hours

What is vorapaxar indicated for?

Patients with a history of MI or peripheral arterial disease (PAD) to reduce thrombotic cardiovascular events

What antiplatelet therapy was vorapaxar used with in clinical trials?

Aspirin and/or clopidogrel

What is the dose of vorapaxar?

2.08 mg (1 tablet) PO daily

What is the boxed warning for vorapaxar?

Bleeding risk (including intracranial hemorrhage and fatal bleeding)

When should vorapaxar NOT be used?

History of stroke, TIA, intracranial hemorrhage, or active serious bleeding

What warning is associated with vorapaxar?

Do not use in severe liver impairment

What are the major side effects of vorapaxar?

Bleeding and anemia

What is the major drug interaction with vorapaxar?

It is a CYP3A4 substrate and a P-gp inhibitor

Which medications should be avoided with vorapaxar?

Strong CYP3A4 inhibitors and strong CYP3A4 inducers

How do fibrinolytics work?

They bind to fibrin and convert plasminogen to plasmin, causing fibrinolysis (clot breakdown)

Which type of ACS are fibrinolytics used for?

STEMI only

When should fibrinolytic therapy be given for STEMI?

When PCI is not available and there are no contraindications;

Within 30 minutes of hospital arrival (door-to-needle time)