Acute Coronary Syndrome Medication Bundle

The acute coronary syndrome medication bundle is the set of drugs started in the first hours and continued at discharge to limit infarct size and prevent further events. It includes aspirin, a P2Y12 inhibitor, anticoagulation, reperfusion where indicated, pain relief and oral secondary prevention drugs. Time to reperfusion is the main determinant of outcome in ST-elevation myocardial infarction. Primary percutaneous intervention is preferred, and fibrinolysis is used when it cannot be done within 120 minutes of diagnosis.

Fibrinolysis in East Africa. Where intervention is not available, give fibrinolysis within 30 minutes of arrival if no contraindication, then transfer for angiography within 2 to 24 hours.

Contraindications to fibrinolysis. Previous intracranial haemorrhage, ischaemic stroke in the last 6 months, intracranial tumour or vascular lesion, recent major trauma or surgery, active bleeding, aortic dissection and severe uncontrolled hypertension (over 180/110 mmHg).

Antiplatelets. Aspirin 300 mg chewed. Then ticagrelor 180 mg orally (or prasugrel 60 mg at intervention, or clopidogrel 300 to 600 mg). With fibrinolysis give clopidogrel 300 mg (75 mg if age is over 75 years). Maintenance aspirin 75 to 100 mg and the P2Y12 inhibitor for 12 months.

Anticoagulation. Unfractionated heparin 70 to 100 units/kg intravenously at intervention. With fibrinolysis, heparin 60 units/kg (maximum 4000 units) then 12 units/kg/hour (maximum 1000 units/hour), or enoxaparin 30 mg intravenous bolus then 1 mg/kg subcutaneously twice daily (no bolus and 0.75 mg/kg, maximum 75 mg, for the first two doses at age 75 or over; 1 mg/kg once daily if creatinine clearance is under 30 mL/min). In non-ST-elevation syndromes, fondaparinux 2.5 mg subcutaneously once daily, avoiding it if creatinine clearance is under 20 mL/min.

Fibrinolytics. Tenecteplase single intravenous bolus by weight: 30 mg under 60 kg, 35 mg for 60 to 69 kg, 40 mg for 70 to 79 kg, 45 mg for 80 to 89 kg, 50 mg for 90 kg or more; use half dose at age 75 or over. Alteplase 15 mg bolus, then 0.75 mg/kg over 30 minutes (maximum 50 mg), then 0.5 mg/kg over 60 minutes (maximum 35 mg). Streptokinase 1.5 million units over 30 to 60 minutes, which is more widely available in East Africa but is allergenic and is not repeated within 6 to 12 months; watch for hypotension.

Pain and symptoms. Glyceryl trinitrate 400 micrograms sublingually, then an infusion starting at 10 to 20 micrograms/minute for continuing pain, hypertension or heart failure; avoid with systolic pressure under 90 mmHg, right ventricular infarction or phosphodiesterase inhibitor use. Morphine 2.5 to 5 mg intravenously for severe pain only, since it delays oral P2Y12 absorption. Oxygen only if saturation is under 90%.

Oral drugs within 24 hours. Bisoprolol 2.5 mg or metoprolol tartrate 25 mg orally twice daily if there is no heart failure, shock or heart block. Ramipril 2.5 mg twice daily or lisinopril 5 mg once daily if there is anterior infarction, ejection fraction of 40% or under, heart failure or diabetes. Atorvastatin 80 mg once daily. Pantoprazole 40 mg once daily if bleeding risk is high.

Within 3 to 14 days. Eplerenone 25 mg once daily, increased to 50 mg, if ejection fraction is 40% or under with heart failure or diabetes, with potassium under 5.0 mmol/L and eGFR over 30 mL/min/1.73 m2. Add an SGLT2 inhibitor for heart failure or diabetes.

Special groups. In older adults avoid prasugrel at 75 or over and use reduced fibrinolytic doses. In pregnancy involve a cardiologist at once, since many of the drugs are unsuitable. In creatinine clearance under 30 mL/min adjust enoxaparin and avoid fondaparinux. In hepatic impairment avoid ticagrelor and prasugrel in severe disease.

Monitoring. Continuous ECG, repeat ECG at 60 to 90 minutes after fibrinolysis (failure if ST resolution is under 50%, which needs rescue angiography), troponin, creatinine, potassium, haemoglobin and platelets. Check platelets at day 5 to 10 on heparin for thrombocytopenia.

Bleeding. Watch for bleeding at the puncture sites, intracranial haemorrhage and falls in haemoglobin. Stop heparin and fibrinolytic infusion for major bleeding.

Beta blocker and ACE inhibitor. Hold for hypotension, bradycardia, heart block, shock or acute kidney injury.

Switching. De-escalate the P2Y12 inhibitor to clopidogrel 75 mg daily if bleeding risk is high.

Stopping. Never stop dual antiplatelet therapy early after a stent. Stop the heparin after intervention or after 48 hours, whichever is first.

Common errors. Delay in giving aspirin, fibrinolysis outside the time window, missing the discharge secondary prevention bundle, aspirin over 100 mg with ticagrelor, and no glyceryl trinitrate spray at discharge.

Referral and escalation. Refer urgently for cardiogenic shock, heart failure, ventricular arrhythmia, ongoing pain, failed fibrinolysis or mechanical complications. Refer all people for angiography after fibrinolysis.