9/27/2019 1 Don’t Break My Heart: Acute Coronary Syndromes Chancey Carothers, PharmD, BCCCP Clinical Pharmacy Specialist, Critical Care Medicine Orlando Regional Medical Center www.fshp.org Disclosure I do not (nor does any immediate family member) have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias this presentation. Pharmacist Objectives • Recall diagnostic differences between unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI) • Define appropriate emergency room treatment principles for acute coronary syndromes (ACS) • State clinical controversies in the early management of ACS • Summarize pharmacotherapy used for in-hospital treatment of ACS • Outline the major pharmacotherapeutic differences in the management of UA/NSTEMI and STEMI Technician Objectives • Distinguish differences in acuity in patients presenting with UA, NSTEMI, or STEMI • Identify medications commonly used in the emergency room for acute coronary syndromes • List adjunctive medications used in percutaneous coronary interventions Scope of the Problem • Healthcare burden: – $150 billion/year in direct and indirect costs – Mortality 18-23% over the age of 40 within 1 year of initial event – 20% of patients are re-hospitalized within 1 year • Hospital burden: – 10-15% of all visits are chest pain related – 2-5% receive a final diagnosis of ACS – 1.5 million discharges Kolansky D. Am J Managed Care. 2009 Galli C. Ann Transl Med. 2016 Acute Coronary Syndrome • Sudden imbalance of myocardial oxygen consumption and demand • Constellation of symptoms reflecting ischemic changes in coronary arteries – Anxiety – Chest pain – Diaphoresis – Dyspnea – Referred pain (arm, jaw, back) – Nausea & Vomiting Amsterdam E. Circulation. 2014 1 2 3 4 5 6
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Pharmacist Objectives Technician Objectives · 2019-10-01 · death, nonfatal MI, or stroke • Secondary outcomes: severe ischemia, heart failure, and need for revascularization
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9/27/2019
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Don’t Break My Heart: Acute Coronary Syndromes
Chancey Carothers, PharmD, BCCCPClinical Pharmacy Specialist, Critical Care Medicine
Orlando Regional Medical Center
www.fshp.org
Disclosure
I do not (nor does any immediate family member) have a vested interest in or affiliation with any corporate organization offering financial support or grant monies for this continuing education activity, or any affiliation with an organization whose philosophy could potentially bias this presentation.
Pharmacist Objectives
• Recall diagnostic differences between unstable angina (UA), non-ST-elevation myocardial infarction (NSTEMI), and ST-elevation myocardial infarction (STEMI)
• State clinical controversies in the early management of ACS
• Summarize pharmacotherapy used for in-hospital treatment of ACS
• Outline the major pharmacotherapeutic differences in the management of UA/NSTEMI and STEMI
Technician Objectives
• Distinguish differences in acuity in patients presenting with UA, NSTEMI, or STEMI
• Identify medications commonly used in the emergency room for acute coronary syndromes
• List adjunctive medications used in percutaneous coronary interventions
Scope of the Problem
• Healthcare burden:– $150 billion/year in direct and indirect costs
– Mortality 18-23% over the age of 40 within 1 year of initial event
– 20% of patients are re-hospitalized within 1 year
• Hospital burden:– 10-15% of all visits are chest pain related
– 2-5% receive a final diagnosis of ACS
– 1.5 million discharges
Kolansky D. Am J Managed Care. 2009Galli C. Ann Transl Med. 2016
Acute Coronary Syndrome
• Sudden imbalance of myocardial oxygen consumption and demand
• Constellation of symptoms reflecting ischemicchanges in coronary arteries – Anxiety
– Chest pain
– Diaphoresis
– Dyspnea
– Referred pain (arm, jaw, back)
– Nausea & Vomiting
Amsterdam E. Circulation. 2014
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Libby P. NEJM. 2013
Acute Coronary Syndromes
• Unstable angina– Ischemic symptoms without cardiac biomarkers
• NSTEMI– Ischemic symptoms with cardiac biomarkers
• STEMI– Ischemic symptoms with persistent ST-elevation and
cardiac biomarkers
EKG Goals
• STAT 12- lead EKG and interpretation within 10 minutes of presentation
• Serial EKGs every 15-30 minutes if symptoms continue
• Pre-hospital, electronic transmission has greatly improved response times
Troponins
• Structural components of myofilaments regulating muscle contraction
• Muscle damage (i.e. ischemia) results in the spillage of troponins C, I, and T into circulation
• 1980’s- 1st cardio selective radioimmunoassay– Detects cardiac isoforms of I and T
– Rapid results in <15 minutes
• Troponins > 0.05 ng/ml are suggestive of some process, >0.4 ng/ml reflects increased mortality
Galli C. Ann Transl Med. 2016. Antman EM. NEJM. 1996 Bolooki H.M. Cleveland Clinic. 2010
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Pharmacist Question
A 55 year old woman presents to the ED with upper abdominal pain radiating to the back. A STAT EKG is ordered and shows ST-depression and labs return with a troponin of 3 ng/ml. Which of the following is the most likely etiology of the abdominal pain?
a) Unstable angina
b) STEMI
c) NSTEMI
d) Gastroparesis
Pharmacist Question
A 55 year old woman presents to the ED with upper abdominal pain radiating to the back. A STAT EKG is ordered and shows ST-depression and labs return with a troponin of 3 ng/ml. Which of the following is the most likely etiology of the abdominal pain?
• Study treatment duration: 6-15 months• Primary endpoint: composite of cardiovascular
related death, nonfatal MI, or stroke• Safety endpoint: Major/life threatening bleeding
not related to CABG and major and minor bleeding
Wiviott. NEJM. 2007.
TRITON ResultsResult Clopidogrel (n= 6716) Prasugrel (n= 6741) p value
Primary endpoint 12.1% 9.9% <0.001
Cardiovascular death 2.4% 2.1% 0.31
Nonfatal MI 9.5% 7.3% <0.001
Nonfatal stroke 1.0% 1.0% 0.93
Death from any cause 3.2% 3.0% 0.64
Stent thrombosis 2.4% 1.1% <0.001
Non-CABG major bleeding
1.8% 2.4% 0.03
Major or minorbleeding
3.8% 5.0% 0.002
Bleeding requiring transfusion
3.0% 4.0% <0.001
Wiviott. NEJM. 2007.
TRITON Results
• Subgroup analysis performed revealed no benefit from/harm from prasugrel in certain populations– History of stroke or TIA: no clinical benefit, net harm
(mostly due to bleeding)
– Age ≥75 years: no benefit over clopidogrel
– Body weight <60 kg: no benefit over clopidogrel
• Among patients without these risk factors– Prasugrel more effective than clopidogrel
– No significant difference in bleeding
Wiviott. NEJM. 2007.
Ticagrelor in ACS (PLATO Study)
• 18,624 patients with ACS in the previous 24 hours
• Aspirin 75-100 mg, plus intervention– Clopidogrel
• 300 mg load (if not on previously), then 75 mg daily
• Additional 300 mg load with PCI
– Ticagrelor• 180 mg load, 90 mg twice daily
• Additional 90 mg dose with PCI >24 hours from admission
• Study treatment duration: 12 months
• Primary endpoint: composite of death from vascular cause, MI, or stroke
• Safety endpoint: first occurrence of any major bleeding
Wallentin. NEJM. 2009.
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PLATO Results
Result Clopidogrel (n= 9291) Ticagrelor (n= 9333) p value
Primary end point 11.7% 9.8% <0.001
MI 6.9% 5.8% 0.005
Death from vascular causes 5.1% 4.0% 0.001
Stroke 1.3% 1.5% 0.22
Mortality 5.9% 4.5% <0.001
Major bleeding 11.2% 11.6% 0.43
Fatal intracranial bleeding 0.01% 0.1% 0.02
Dyspnea 7.8% 13.8% <0.001
Discontinuation of medication
21.5% 23.4% 0.002
Wallentin. NEJM. 2009.
Ticagrelor and Aspirin
• Ticagrelor superior to clopidogrel everywhere except North America
• Median aspirin dose ≥300 mg/day in 54% of North America patients vs <2% elsewhere
• No benefit from ticagrelor seen in subgroup analysis of patients with aspirin doses >100 mg/day
• FDA black box warning: maintenance doses of aspirin above 100 mg reduce the effectiveness of ticagrelor and should be avoided
DAPT SelectionClopidogrel Prasugrel Ticagrelor
Advantages
Once daily administration Once daily administration More efficacious than clopidogrel
Cheapest option More efficacious thanclopidogrel
No activation required
Lack of drug interactions Lack of drug interactions
Disadvantages
Less effective Higher risk of bleeding Twice daily administration
Prodrug that requires activation
More expensive More expensive
Drug interactions*
Coronary Stents
Bare Metal Stent (BMS)
• No drug released by stent
• High risk of short term in stent thrombosis
• High risk of long term in stent restenosis
• DAPT recommended for 12 months
Drug Eluting Stent (DES)
• Slowly releases paclitaxel, sirolimus, or evirolimus
• Reduces the risk of long term in stent restenosis
• Increases the long term risk of in stent thrombosis
• Slowly releases paclitaxel, sirolimus, or evirolimus
• Reduces the risk of long term in stent restenosis
• Increases the long term risk of in stent thrombosis
• DAPT therapy recommended for at least12 months
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Pharmacist Assessment
Which of the following dual antiplatelet regimens would be appropriate for a patient who just received a drug eluting stent?A. Aspirin 81 mg daily plus prasugrel 10 mg dailyB. Clopidogrel 75 mg daily plus ticagrelor 90 mg
dailyD. Prasugrel 10 mg daily plus ticagrelor 90 mg
twice daily
Pharmacist Assessment
Which of the following dual antiplatelet regimens would be appropriate for a patient who just received a drug eluting stent?A. Aspirin 81 mg daily plus prasugrel 10 mg dailyB. Clopidogrel 75 mg daily plus ticagrelor 90 mg