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A Pair of ACEIs? What is the Role of ACEIs in Unstable Angina

A Pair of ACEIs? What is the Role of ACEIs in Unstable Angina. Matthew Brons Sukhjinder Sidhu Interior Health Pharmacy Residents Cardiology Rotation November 28, 2013. Learning Objectives. By the end of this 45-min session the audience should be able to:

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A Pair of ACEIs? What is the Role of ACEIs in Unstable Angina

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  1. A Pair of ACEIs?What is the Role of ACEIs in Unstable Angina Matthew Brons Sukhjinder Sidhu Interior Health Pharmacy Residents Cardiology Rotation November 28, 2013

  2. Learning Objectives • By the end of this 45-min session the audience should be able to: • Describe the pathophysiology and clinical presentation of unstable angina (UA) • Compare and contrast the diagnostic criteria of UA, NSTEMI and STEMI • State the evidence for ACEI in UA • State the benefits of ACEI in patients with decreased LVEF, high risk CAD and ACS • Be able to determine the need for ACEI in an UA patient

  3. WA

  4. WA

  5. Review of Systems (WA)

  6. Investigations (WA)

  7. Angiogram (WA)

  8. Current Problems & Medications (WA)

  9. DRP’s • WA is at increased risk of developing morbidity complications (e.g. MI, HF) and mortality secondary to not receiving an ACE inhibitor and would benefit from the initialization of therapy • WA is at risk of developing severe hypotension secondary to a drug-drug interaction with nitroglycerin and sildenafil and would benefit from counselling. • WA is at risk of developing influenza and pneumonia secondary to not receiving vaccinations and would benefit from administration of vaccinations. • WA is at risk of experiencing adverse effects secondary to receiving a high dose of atenolol and would benefit from increased monitoring of his BP and HR. • WA is at increased risk of developing CV and respiratory complications (e.g. MI, COPD) and death secondary to smoking and would benefit from additional counselling. • WA is at risk of developing macrovascular and microvascular complications secondary to not receiving drug therapy for type II diabetesand may benefit from initialization of therapy. • WA is at risk of developing CV complications (e.g. MI, HF, stroke) secondary to a history of non-adherence to medications and would benefit from counselling.

  10. BL

  11. BL

  12. Review of Systems (BL)

  13. Investigations (BL)

  14. Angiogram (BL)

  15. Current Problems & Medications (BL)

  16. DRP’s • BL is at risk of recurrent MI and death secondary to not receiving an ACEI and would benefit from optimization of ACS therapy. • BL is at risk of experiencing recurrent MI and death secondary to smoking and would benefit from smoking cessation. • BL is at risk of experiencing recurrent MI, worsening heart function and death secondary to ibuprofen use and would benefit from discontinuing ibuprofen and counseling on its adverse effects. • BL is at risk of experiencing influenza(fever, night sweats, myalgias, fatigue, nausea, vomiting, diarrhea) secondary to not receiving an influenza vaccine and would benefit from receiving the influenza vaccine. • BL is experiencing a mild rash secondary to the adhesives on the ECG strips and nicotine patch and would benefit from receiving a topical corticosteroid formulation.

  17. DRP Focus • WA and BL are at risk of experiencing cardiovascular morbidity (e.g. MI, HF) and mortality secondary to not receiving an ACEI and would benefit from optimization of ACS therapy.

  18. Unstable Angina • Angina is caused by poor blood flow through the coronary vessels of the myocardium • Acute reduction in myocardial oxygen supply • CAD due to atherosclerosis is the most common cause of UA heartcurrents.com

  19. Unstable Angina

  20. Acute Coronary Syndromes

  21. Goals of Therapy • Prevent mortality • Minimize myocardial damage and total ischemic time • Establish and maintain patency of the infarct-related artery • Alleviate signs and symptoms • Prevent re-occlusion, re-infarction, re-hospitalization • Minimize adverse events • Promote smoking cessation

  22. Therapeutic Approach • ASA 81 mg PO daily • P2Y12 inhibitors • High dose statin • Beta-blockers • RAAS inhibitors • Nitroglycerin PRN

  23. RAAS Inhibitors • Improve endothelial function • Inhibit hypertrophy • Increase bradykinin • increases nitric oxide production = vasodilation • Blood pressure control

  24. Background • ACC/AHA Guidelines for UA/NSTEMI • An ACEI for all post-ACS patients (Level of Evidence: B) • ACEIs have been shown to reduce mortality rates in patients with AMI and in patients with recent MI or with LV systolic dysfunction, in diabetic patients with LV dysfunction, and in a broad spectrum of patients with high-risk chronic CAD • ACEI for patients with CHF, LV dysfunction (EF < 0.40), HTN, or diabetes (Level of Evidence: A) ACC/AHA 2007 Guidelines for UA/NSTEMI

  25. Clinical Question

  26. Literature Search

  27. HOPE NEJM 2000 342:3;145-53

  28. HOPE NEJM 2000 342:3;145-53

  29. HOPE Author’s conclusions: • “Our findings show that ramipril, an angiotensin-converting-enzyme inhibitor, is beneficial in a broad range of patients without evidence of left ventricular systolic dysfunction or heart failure who are at high risk for cardiovascular events.” NEJM 2000 342:3;145-53

  30. HOPE Strengths • Large and extensive trial Limitations • Not all patients were screened for reduced LVEF • Patients may not have been receiving optimal therapies for their co-morbidities Generalizability • Patient has DM and HTN • No reduced LVEF NEJM 2000 342:3;145-53

  31. EUROPA LANCET 2003 362;782-88

  32. EUROPA LANCET 2003 362;782-88

  33. EUROPA Author’s conclusions: • “We show a substantial benefit with perindopril in a broad population of patients with stable coronary artery disease and no evidence of heart failure or notable hypertension.” LANCET 2003 362;782-88

  34. EUROPA Strengths • Large and extensive trial Limitations • Patients may not have been receiving optimal therapies for their co-morbidities Generalizability • Patient has DM and HTN • No impaired LVEF • CABG patients

  35. Summary of Evidence

  36. Clinical Question

  37. HOPE and EUROPAApplicable to BL?

  38. Literature Search

  39. Milonas et al. • N~38000, prospective observational trial • ACEI treatment at discharge = 24% ↓ 1-year mortality • driven by those with hx or current signs of HF • In patients without HF, no significant benefit of ACEI • Except in those with at least moderate renal dysfunction AM J Cardiol 2010; 105:1229-1234

  40. PEACE NEJM 2004; 351:205-68

  41. PEACE NEJM 2004; 351:205-68

  42. PEACE • Author’s conclusions: • PEACE Trial does not demonstrate the benefits of ACE inhibition shown by HOPE and EUROPA because the patients enrolled in the PEACE Trial were at lower risk for CV events • In a population of patients with CAD and preserved EF who receive intensive current therapy, usually including coronary revascularization and lipid-lowering agents, and in whom the rate of CV events are therefore already quite low, there appears to be no evidence of CV benefit from the addition of ACEI therapy NEJM 2004; 351:205-68

  43. PEACE • Strengths • ITT • High compliance (82% - 1yr; 79% -2yr; 75% - 3yr) • Majority of patients receiving appropriate cardiac medications • Limitations • Patients in the placebo arm who had DM with HTN or had proteinuria were given an ACEI as open-label • Generalizability • Population included was low-risk • Majority of patients had received revascularization NEJM 2004; 351:205-68

  44. IMAGINE Circulation. 2008; 117:24-31

  45. IMAGINE Circulation. 2008; 117:24-31

  46. IMAGINE • Author’s conclusions: • At least in low risk-patients treated with contemporary therapy, early initiation of an ACEI after CABG has no benefit, and this strategy may even be associated with an increase in adverse events Circulation. 2008; 117:24-31

  47. IMAGINE • Strengths • High compliance • Large number of patients receiving appropriate cardiac medications • Limitations • Would results be similar if ACEI started prior to surgery? • Stroke and CHF added to primary outcome due to low event rate • Generalizability • Patient had CABG surgery Nov 21, 2013 • Normal LVEF • Excluded DM patients Circulation. 2008; 117:24-31

  48. Summary of Evidence

  49. Application to WA and BL

  50. Therapeutic Plan WA • Initiate ramipril 5 mg PO daily, titrating up to target dose of 10 mg PO daily as appropriate • Administer influenza vaccine 0.5 mL IM x 1 • Administer pneumococcal vaccine 0.5 mL IM x1 • Provided adherence strategies for all ACS medications • Re-enforced need to continue with smoking cessation BL • Do not initiate an ACEI • Administer influenza vaccine 0.5 mL IM x 1 • Hydrocortisone cream 1% apply to affected areas BID PRN • Provided counseling regarding A/E of NSAID use • Provided counseling on the use of acetaminophen over NSAIDs for OA pain • Provided counseling and reinforcement regarding smoking cessation

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