A Pair of ACEIs? What is the Role of ACEIs in Unstable Angina Matthew Brons Sukhjinder Sidhu...
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A Pair of ACEIs? What is the Role of ACEIs in Unstable Angina Matthew Brons Sukhjinder Sidhu Interior Health Pharmacy Residents Cardiology Rotation November
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
Slide 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
Slide 3
WA ID65 y.o. male (132kg, 185cm) admitted November 11 th CC/HPI
Severe chest pain (tightness) SOBOE and chest pain on exertion -8
month hx of intermittent episodes of discomfort Diagnosed with UA
and to be medically managed until follow-up SCA +/- PCI
AllergiesNKDA Social Hx 3 pack per day smoker x 40 years No
alcohol/illicit drugs Family HxFather stroke at age 54
VaccinationsNot up-to-date
Slide 4
WA PMHMPTA GERD Esomeprazole 40 mg PO daily Only takes
PRN/infrequently Smoking Cessation Varenicline 1 mg PO BID Never
completed full treatment, was not ready to quit HTNAtenolol 100 mg
PO daily EDSildenafil 50 mg PO PRN DyslipidemiaAtorvastatin 20 mg
PO QHS stopped taking in March Type II DMDiet Controlled
Slide 5
Review of Systems (WA) VITALSTemp: 36.8 o C BP: 121/83 HR: 77
RR: 18 O2Sat: 96% RA CNS/NEUROA & O x 3 HEENTNormal CVSDistant
heart sounds, no extra sounds/rubs/clicks or murmurs RESPClear
GISoft, non-tender GUNormal MSK/DERMNormal ENDORandom glucose 7.2,
A1C 6.8% LYTESNa 139 K 4.5 Cl 103 Bicarb 27 SrCr 96 HEMEHgb 158 WBC
10.8 Plts 334 INR 1.2 TROP < 0.04 LIPIDSTG 2.08 LDL 1.37 HDL
0.79
Slide 6
Investigations (WA) Diagnostics Day 0ECG Day 2AngiogramLeft
Main: Severe Disease LAD: Moderate mid-vessel disease Circumflex:
Proximal occlusion RCA: Moderate proximal disease Not a PCI
candidate CABG referral Day 4TTENormal LV EF 45 50%
Slide 7
Angiogram (WA)
Slide 8
Current Problems & Medications (WA) Medical ProblemCurrent
Medications UA Atorvastatin 80 mg PO daily Atenolol 100 mg PO BID
ASA 81 mg PO daily Nitroglycerin spray 0.4 mg 1-2 sprays SL Q5min
PRN Nitroglycerin IV HypertensionAtenolol 100 mg PO BID Type II
DiabetesDiet Controlled Smoking CessationNicotine patch 42 mg TDERM
daily GERDPantoprazole 40 mg PO daily
Slide 9
DRPs 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
diabetes and 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.
Slide 10
BL ID53 y.o. male (133 kg; 183 cm) Admitted Nov 9 th to OMH and
transferred to KGH Nov 12 th CC/HPISub-sternal chest discomfort
(burning) x 2 episodes SOBOE x months prior to event Diagnosed with
UA and to be medically managed until follow-up SCA +/- PCI
AllergiesAnti-inflammatory (name?) hives Social Hx80 pack-year
smoking hx EtOH or illicit drugs influenza immunization
Slide 11
BL PMHx:MPTA: OAAcetaminophen 500 mg PO PRN (500 mg Q3days)
Ibuprofen 600-1200 mg PO daily Asthma/COPDAdvair 250/50 1 INH BID
PRN Salbutamol 100-200 mcg INH Q4H PRN General HealthMultivitamin 1
tab PO daily
Slide 12
Review of Systems (BL) VitalsT 36.5 HR 56 BP 119/81 RR 18 O2
sat 99% (RA) CNS/NeuroA&O x 3 HEENT RESP CVS GI GUSrCr 83; eGFR
84 ENDOGlu 4.0; TG 3.83; Chol 3.32; LDL 0.85; HDL 0.71 MSK/Derm
CHEMNa 141 K 4.3 Trop
EUROPA DRandomized, double-blind, multicentre, n = 12 218 P -18
+ -Hx of CAD documented by previous MI, PCI or CABG, or
angiographic evidence of 70% + narrowing of one or more major
coronary arteries; Men with positive ECG, echo, or nuclear stress
test and chest pain -Excluded: -HF, planned revascularisation,
hypotension (SBP 180, DBP > 100), recent use of ACE or ARB,
renal insufficiency, high serum potassium -Baseline: -CABG ~ 30%;
HTN ~ 27%; DM ~ 12%; Angiogram ~ 60% I / C-Perindopril 8 mg PO
Daily vs. placebo O-Composite of CV death, non-fatal MI, cardiac
arrest with successful resuscitation LANCET 2003 362;782-88
EUROPA Authors 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
Slide 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
Slide 35
Summary of Evidence OutcomesHOPEEUROPA -Hx of CAD, stroke, PVD
or DM + HTN, cholesterol, smoker, or microalbuminuria -Ramipril 5
mg PO daily vs. placebo -over 4.6 yrs -Hx CAD: MI, PCI, CABG; or
70% narrowing of coronary artery -Perindopril 8 mg PO daily vs.
placebo -over 4.2 yrs Reduce risk of mortalitySS Reduce risk of
future myocardial infarctions SS Adverse event Cough
Hypotension
Slide 36
Clinical Question WABL P UA with hx of type II DM, HTN &
CAD awaiting CABG UA awaiting CABG I ACEI + ACS therapy (ASA,
atorvastatin, beta-blocker) C Placebo + ACS therapy (ASA,
atorvastatin, beta-blocker) O Decrease mortality Prevent future MIs
Increased risk of adverse events
Slide 37
HOPE and EUROPA Applicable to BL? HOPEEUROPA BaselinePrevious
MI 52% Revascularization 40% DM 39% HTN 47% Chol > 5.2 mmol/L
66% BB 40% Lipid-lowering agents 29% Previous MI 65%
Revascularization 54% DM 12% HTN 27% Chol > 6.5mmol/L 63% BB 62%
Lipid-lowering agents 58%
Slide 38
Literature Search DatabasesGoogle Scholar, Medline, Embase
Search TermsAngiotensin-Converting Enzyme Inhibitors Cardiovascular
diseases or heart diseases LimitsEnglish language and (guideline or
meta analysis or RCT or systematic review) Results2 relevant
meta-analysis 6 relevant RCTs -PEACE -IMAGINE 1 relevant
observational study
Slide 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
Slide 40
PEACE DDB, PC, MC RCT, N=8290 PInclusion: > 50 y.o.; CAD
(MI, CABG, PCI > 3 mo before enrollment; > 50% block of >
1 coronary vessel); LVEF > 40% > 80% compliance with meds in
run-in phase Baseline: Mean age 64; 82% men; 55% prev. MI; 61% CAD;
72% revascularization; 17% DM; 45% HTN; 12% DM + HTN; SBP 134 +/-
17; EF 58 +/- 10%; 60% BB; 90% antiplatelet; 70% lipid lowering I /
CTrandolapril 4mg PO daily vs. placebo x mean duration 4.8 years
OComposite of death from CV causes, nonfatal MI, or
revascularization NEJM 2004; 351:205-68
Slide 41
PEACE TrandolaprilPlaceboHR95% CI CV death, nonfatal MI,
revascularization 21.9%22.5%0.960.88 1.06 NSS CV death
3.5%3.7%0.950.76 1.19 Non-fatal MI 5.3% 1.000.83 1.20 NEJM 2004;
351:205-68
Slide 42
PEACE Authors 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
Slide 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
Slide 44
IMAGINE DDB, PC, PG, MC RCT, N=2553 PInclusion: Post-CABG 18
y.o.; LVEF > 40% Baseline: Mean age 61; 87% men; 10% DM; 47%
HTN; LVEF 60%; SBP 122 +/- 14; 91% ASA; 65% statin; 79% BB; 23%
ACEI I / CQuinapril 10 or 20 mg PO daily to target of 40 mg PO
daily vs. placebo x 2.95 yrs OComposite of CV death, resuscitated
cardiac arrest, nonfatal MI, coronary revascularization, UA
requiring hospitalization, angina, stroke and CHF Circulation.
2008; 117:24-31
IMAGINE Authors 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
Slide 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
Slide 48
Summary of Evidence OutcomesPEACEIMAGINE -CAD, LVEF > 40%,
low CV risk factors -on ASA, statin and BB, -trandolapril 4 mg PO
daily vs. placebo -over 4.8 yrs -Post CABG ( 40% and no DM
-Quinapril to target of 40 mg PO daily vs. placebo -over 2.95 yrs
Reduce risk of mortalityNSS Reduce risk of future myocardial
infarctions NSS Adverse event Cough and syncope Cough and
hypotension
Slide 49
Application to WA and BL WABL Necessary CV risk factors present
DM, HTN, prior MI hx Effective? Safe Adherence?
Slide 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
Slide 51
Monitoring Plan EfficacyWhen S: MI symptoms -Chest pain Daily
O:BP ( 30%, K > 5 mmol/LDaily post-CABG until stable, then 1-2
weeks post dose increase as outpatient, then with routine
outpatient blood work thereafter
Slide 52
Follow Up WA Ramipril 5 mg PO daily initiated Influenza and
pneumococcal vaccine to be given as outpatient Metformin 500 mg PO
BID initiated WA appeared receptive to smoking cessation and
importance of adherence to medications Successful CABG BL ACEI not
initiated Influenza vaccine administered BL receptive to smoking
cessation BL receptive to avoiding use of NSAID and using
acetaminophen for pain control Successful CABG
Slide 53
Conclusion No studies have evaluated ACEI solely in UA patients
ACEI decreased CV death and non-fatal MI in UA if other risk
factors are present HTN, DM, chol, or LVEF ACEI have not shown
similar results in low CV risk patients
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