Transcript Document

Medication Management
and Secondary Prevention
Post PCI
Kimberly J. Richards, Pharm.D., RPh
Director of Pharmacy Services
Baptist Health Richmond
Diagnostic Cardiac Catheterization vs.
PTCA Number of Procedures Performed
Coronary Heart Disease
Syndromes And Interventional
Procedures
 1.6 million hospital discharges for ACS in the U.S. in
2003.
 Roughly 30% of ACS patients have STEMI.
 ~ 2.7 million heart catheterizations are done in the US
annually.
 ~ 1/3 of these require coronary intervention
(~900,000/year).
 The majority of interventional procedures involve the
use of endovascular stents.
 Approximately 1 million coronary stents are
implanted in the US annually (~ 1.3 stents per
patient)
Classification of Recommendations and Levels of Evidence
A recommendation with
Level of Evidence B or C
does not imply that the
recommendation is weak.
Many important clinical
questions addressed in
the guidelines do not lend
themselves to clinical
trials. Although
randomized trials are
unavailable, there may be
a very clear clinical
consensus that a
particular test or therapy
is useful or effective.
*Data available from
clinical trials or registries
about the usefulness/
efficacy in different
subpopulations, such as
sex, age, history of
diabetes, history of prior
myocardial infarction,
history of heart failure,
and prior aspirin use.
†For comparative
effectiveness
recommendations (Class I
and IIa; Level of Evidence
A and B only), studies
that support the use of
comparator verbs should
involve direct
comparisons of the
treatments or strategies
being evaluated.
Use of Stents in Patients With STEMI
I IIa IIb III
Placement of a stent (BMS or DES) is useful in primary PCI for
patients with STEMI.
I IIa IIb III
I IIa IIb III
Harm
BMS* should be used in patients with high bleeding risk, inability
to comply with 1 year of DAPT, or anticipated invasive or surgical
procedures in the next year.
DES should not be used in primary PCI for patients with STEMI
who are unable to tolerate or comply with a prolonged course of
DAPT because of the increased risk of stent thrombosis with
premature discontinuation of one or both agents.
*Balloon angioplasty without stent placement may be used in selected patients.
Stents
• Nearly Eliminated Abrupt Vessel
Closure
• Significantly Reduced Restenosis
• Reduced Urgent CABG
1. Bare Metal
2. Drug Eluting
Long-term Prevention
Short-term Prevention
Secondary and Long-Term
Prevention: Post-PCI
Acute
stent
thrombosis
24 hours
incidence: 0.6%
Sub-acute
stent thrombosis
Late stent
restenosis
Major adverse
cardiac events
Other atherothrombotic
events (all arterial beds)
Days to weeks
incidence: <5%
Up to 12 months
incidence: 15%
First year
incidence: ~20%
Life-long
STENT THROMBOSIS
Presentation with DES Thrombosis
Iakovou: JAMA 2005; 293: 2126-30
Predictors of Late Stent
Thrombosis
•
•
•
•
•
•
•
•
Advanced Age
ACS
Insulin Treated Diabetes
Low Ejection Fraction
Smoking
Renal Failure
Multiple Stents
Suboptimal Stent Results
Risk Factor Modification &
Secondary Prevention
ABCDE’s
•
•
•
•
•
Antiplatelets & Anticoagulation
Blood Pressure Management
Cholesterol & Cessation of Smoking
Diet
Education & Exercise
Dual Anti-Platelet Therapy (DAPT)
• Aspirin
• Thienopyridines
–Ticlopidine (Ticlid®)
–Clopidogrel (Plavix®)
–Prasugrel (Effient®)
–Ticagrelor (Brilinta®)
Main Results of the CURE Trial
Main Results of the PCI-CURE
Study
TABLE I. Antiplatelet Agent Uses
2, 3, 6
Antiplatelet Agent Uses
Clopidogrel
Prasugrel
Ticagrelor
Management of ACS – patients undergoing
PCI with stent placement
Management of ACS – non-invasive
strategy
FDA
approved
FDA
approved
FDA
approved
FDA
approved
*
FDA
approved
Prevention of stroke
FDA
approved
*
*
* Not an FDA approved use
ACS = acute coronary syndrome, PCI=percutaneous coronary intervention
Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III
Aspirin 162 to 325 mg should be given before primary PCI.
I IIa IIb III
After PCI, aspirin should be continued indefinitely.
Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III
P2Y12 inhibitor therapy should be given for 1 year to patients with
STEMI who receive a stent (BMS or DES) during primary PCI
using the following maintenance doses:
• Clopidogrel 75 mg daily; or
• Prasugrel 10 mg daily; or
• Ticagrelor 90 mg twice a day*
*The recommended maintenance dose of aspirin to be used with Ticagrelor is 81 mg
daily.
Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III
It is reasonable to use 81 mg of aspirin per day in preference to
higher maintenance doses after primary PCI.
Antiplatelet Therapy to Support
Primary PCI for STEMI
I IIa IIb III
Prasugrel should not be administered to patients with a history of
prior stroke or transient ischemic attack.
Harm
Blood Clotting
Red Blood Cell
Platelet
Fibrin Mesh
Ticlopidine (Ticlid®)
Initial Oral Thienopyridine
Platelet inhibition 30%
Small Risk of Severe Neutropenia
Need CBC Monitoring
Rare TTP
Use in Patients Unable to Take
Clopidogrel
• Full Antiplatelet Action Takes Several
Days
•
•
•
•
•
•
Pharmacokinetics
Clopidogrel
Prasugrel
Ticagrelor
Distribution:
Plasma protein binding:
N/A
98%
N/A
Time to peak response:
30-60 minutes
30 minutes
1.5 hours
Hepatic
Hepatic
Hepatic
Yes
50% renal, 50% biliary
excretion
Decreased inhibition of
platelet aggregation
(~25%)
Yes
68% renal, 27% biliary
excretion
Exposure to active
metabolite decreased in
patients with severe
renal impairment
No differences
observed
Yes
Biliary excretion
Metabolism:
Active metabolites:
Elimination:
Moderate or severe renal
impairment
In patients with hepatic
impairment
Age
Terminal Half Life
Platelet inhibition:
Maximum platelet
aggregation inhibition at
steady state
Time to normal platelet
function upon
discontinuation
No differences
observed
No difference observed
6 hours
Irreversible
40%-60%, 3-7 days
Increased exposure of
active metabolite
observed in patients
>75 years of age
7 hours
Irreversible
70%-80%, 3-5 days
About 5 days
5-9 days
No differences
observed
Not studied or
recommended in
patients with severe
hepatic impairment
No difference
observed
7 hours
Reversible
80%-90%, 4 weeks
2-3 days
2, 3, 6
Safety Considerations for Antiplatelet Agents
Clopidogrel
Contraindications:
Hypersensitivity to the drug or
its components
Active bleeding
Prior transient ischemic attack
or stroke
Severe hepatic impairment
Precautions:
Extreme caution in patients >
75 years of age or body weight
< 60 kg
Caution in patients with
impaired CYP2C19 function
(genetic variations, drug
interactions)
Drug Interactions:
Prasugrel
Ticagrelor
X
X
X
X
X
X
---
X
---
---
---
X
---
X
---
X
Omeprazole,
NSAIDs, warfarin
--Warfarin, NSAIDs
--Strong
inducers/inhibitors of
CYP 3A4 (e.g.,
ketoconazole,
voriconazole,
clarithromycin,
dexamethasone,
phenytoin,
carbamazepine)
Clopidogrel
Pediatric Use:
Geriatric Use:
Pregnancy Category:
Nursing Mothers:
Excreted in human milk
Safety and
effectiveness not
established
Effectiveness and
safety not affected by
age
B
Not known
(Rat models detected
drug in milk)
Adverse Events:* (non-bleeding)
Diarrhea
Nausea
Dyspepsia
Rash
Dyspnea
Hypertension
Hypotension
Ventricular pauses
Prasugrel
Ticagrelor
Safety and
effectiveness not
established
Not recommended
in patients > 75
years of age;
increased risk of
bleeding
B
Not known
(Rat models
detected drug in
milk)
Safety and
effectiveness not
established
Use with caution in
elderly patients
2.3%
4.6%
--2.8%
4.9%
7.5%
3.9%
---
3.7%
4.3%
4.8%
0.9%
13.8%
--3.3%
5.5%
2.6%
4.3%
--2.4%
4.5%
7.1%
3.8%
---
*Adverse events for clopidogrel and prasugrel taken from TRITON-TIMI 38 trial11
C
Not known
2, 3, 6
Dosing and Monitoring Recommendations for Antiplatelet Agents:
Indications:
Dosing
Clopidogrel 300-600 mg loading dose, 75 mg daily
ACS – PCI with stent placement Prasugrel 60 mg loading dose, 10 mg daily
Ticagrelor 180 mg loading dose, 90 mg twice daily
ACS – Medical management
Clopidogrel 300-600 mg loading dose, 75 mg daily
Ticagrelor 180 mg loading dose, 90 mg twice daily
Prevention of stroke
Clopidogrel 75 mg daily
Monitoring Recommendations:
Clopidogrel
Signs of bleeding, platelet aggregation studies (suspected nonresponders), CYP2C19 genotype/phenotype (controversial)
Prasugrel
Signs of bleeding
Ticagrelor
Signs of bleeding
Clopidogrel
• Most Commonly Used Thienopyridine in
U.S. and the only one in the class that
is available generically
• Onset of Full Effect within Hours of a
Loading Dose
• Indicated in Patients After NSTEMI, U.A.,
STEMI
Clopidogrel – “Boxed Warning”
Effectiveness is dependent on activation to an active
metabolite via CYP2C19.
Poor metabolizers of CYP2C19 treated with
Clopidogrel at recommended doses exhibit higher
cardiovascular (CV) event rates following acute
coronary syndrome (ACS) or undergoing
percutaneous coronary intervention than patients
with normal CYP2C19 function.
Tests are available to identify a patient's CYP2C19
genotype and to determine therapeutic strategy.
Consider alternative treatment in poor metabolizers.
CLINICAL ALERT
ACCF/AHA Clopidogrel Clinical Alert: Approaches to the FDA "Boxed Warning“;
A Report of the American College of Cardiology Foundation
Task Force on Clinical Expert Consensus Documents and
the American Heart Association Endorsed by the Society for
Cardiovascular Angiography and Interventions and the
Society of Thoracic Surgeons
J Am Coll Cardiol, 2010; 56:321-341, doi:10.1016/j.jacc.2010.05.013 (Published online 28 June 2010).
© 2010 by the American College of Cardiology Foundation
 CYP2C19 polymorphism accounts for only 12% of
variability in Clopidogrel platelet response.
 The positive predictive value of CYP2C19
polymorphisms is estimated to be between 12%
and 20% in patients with ACS undergoing PCI.
Platelet Testing
 Genetic Testing: CYP2C19 – “Poor Metabolizers”
 Platelet Function Testing: (“Verify Now”, TEG,
others) – “Hypo responders” [< 20% platelet
inhibition] *A positive association with an
increased risk of death, MI, and ST
 Both?
 Neither?
Clinical Events as a Function of Proton Pump Inhibitor
Use, Clopidogrel Use, and Cytochrome P450 2C19
Genotype in a Large Nationwide Cohort of Acute
Myocardial Infarction
Results From the French Registry of Acute ST-Elevation and Non–ST-Elevation
Myocardial Infarction (FAST-MI) Registry
Circulation. 2011;123:474-482 January 24, 2011, doi: 10.1161/CIRCULATIONAHA.110.965640
 PPI use was not associated with an increased risk for
in-hospital events (survival, reinfarction, stroke,
bleeding, and transfusion).
 PPI treatment was not an independent predictor of 1year survival (hazard ratio, 0.97; 95% confidence
interval 0.87 to 1.08; P=0.57) or 1-year MI.
 PPI use was not associated with an increased risk of
cardiovascular events or mortality in patients
administered Clopidogrel for recent MI, whatever the
CYP2C19 genotype.
Duration of Therapy Post PCI
• Initially 2-4 weeks
• PCI Cure Trial changed that
– 31% Decreased Risk of CV Death, MI or Stroke with
long term Clopidogrel
– No Increase in Major Bleeding
– Increase in Minor Bleeding
• Credo Trial Found Similar Long Term Benefit
Post—PCI
• Based on these trials it is rec. ASA &
Clopidogrel Post Stenting & PCI go to at
least 1 year
Reasons for Discontinuation
•
•
•
•
•
Cost
Lack of Education and F/U
Older Age
Bleeding/Bruising
Clopidogrel has Lower Risk of Bleeding
than ASA
Methods to Prevent Premature
Discontinuation
• Discuss with Patient BEFORE Stenting
• If Procedure Needed in Next 12
months, Consider BMS or Balloon PTCA
• Educate Patients Post-Procedure
• Instruct Patients to Contact their
Physician Prior to Discontinue any
Medication
• Defer Elective Procedures if Possible
•
•
Antithrombin Therapy
Atrial Fibrillation is the most common
sustained cardiac arrhythmia and occurs
at a frequency of 10% in patients after
acute MI and the lifetime risk of
developing AF at age 55 is ~24% in men &
22% in women
If a Patient needs Warfarin (AF, valve etc.)
and has a Stent Implanted, then ASA +
Clopidogrel + Warfarin are needed
1. ? Increased Risk of Bleeding
2. Recent Registry Data Showed no Increased
Death or Bleed 6 months Post Stent
3. Try and Keep INR Lower ~2.0
4. Consider BMS
5. Each Clinical Situation Will Dictate How
Aggressively to Anticoagulate
Anticoagulation
I IIa IIb III
Anticoagulant therapy with a vitamin K antagonist should be
provided to patients with STEMI and atrial fibrillation with
CHADS2* score greater than or equal to 2, mechanical heart
valves, venous thromboembolism, or hypercoagulable disorder.
I IIa IIb III
The duration of triple-antithrombotic therapy with a vitamin K
antagonist, aspirin, and a P2Y12 receptor inhibitor should be
minimized to the extent possible to limit the risk of bleeding.†
*CHADS2 (Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous
Stroke/transient ischemic attack (doubled risk weight)) score.
†Individual circumstances will vary and depend on the indications for triple therapy and the type of
stent placed during PCI. After this initial treatment period, consider therapy with a vitamin K
antagonist plus a single antiplatelet agent. For patients treated with fibrinolysis, consider triple
therapy for 14 days, followed by a vitamin K antagonist plus a single antiplatelet agent.
Anticoagulation
I IIa IIb III
Anticoagulant therapy with a vitamin K antagonist is reasonable
for patients with STEMI and asymptomatic LV mural thrombi.
I IIa IIb III
Anticoagulant therapy may be considered for patients with
STEMI and anterior-apical akinesis or dyskinesis.
I IIa IIb III
Targeting vitamin K antagonist therapy to a lower international
normalized ratio (e.g., 2.0 to 2.5) might be considered in patients
with STEMI who are receiving DAPT.
Long-term Prevention
Short-term Prevention
Secondary and Long-Term
Prevention: Post-PCI
Acute
stent
thrombosis
24 hours
incidence: 0.6%
Sub-acute
stent thrombosis
Late stent
restenosis
Major adverse
cardiac events
Other atherothrombotic
events (all arterial beds)
Days to weeks
incidence: <5%
Up to 12 months
incidence: 15%
First year
incidence: ~20%
Life-long
DES vs BMS
TAXUS IV
SIRIUS
40%
Overall
Restenosis
36.3%
35%
30%
26.6%
25%
20%
15%
10%
8.9%
7.9%
5%
T=Paclitaxel
S=Sirolimus
0%
T
Control
S
Control
Restenosis
• Occurs over 1 to 8 months post PCI
• Presenting symptoms include
– exertional angina (25% to 85%)
– unstable angina (11 to 41%)
– MI (1 to 6%)
Levine, Clin Cardiol. 1995;18:693-703
Risk Factor Modification
ABCDE’s
•
•
•
•
•
Antiplatelets & Anticoagulation
Blood Pressure Management
Cholesterol & Cessation of Smoking
Diet
Education & Exercise
Blood Pressure Control
Recommendations
Goal: <140/90 mm Hg or <130/80 if
diabetes or chronic kidney disease
I IIa IIb III
I IIa IIb III
Blood pressure 120/80 mm Hg or greater:
Initiate or maintain lifestyle modification: weight control,
increased physical activity, alcohol moderation, sodium
reduction, and increased consumption of fresh fruits vegetables
and low fat dairy products
Blood pressure 140/90 mm Hg or greater (or 130/80 or
greater for chronic kidney disease or diabetes)
As tolerated, add blood pressure medication, treating initially
with beta blockers and/or ACE inhibitors with addition of other
drugs such as thiazides as needed to achieve goal blood
pressure
Beta Blockers
I IIa IIb III
Oral beta blockers should be initiated in the first 24 hours in
patients with STEMI who do not have any of the following: signs
of HF, evidence of a low output state, increased risk for
cardiogenic shock,* or other contraindications to use of oral beta
blockers (PR interval >0.24 seconds, second- or third-degree
heart block, active asthma, or reactive airways disease).
I IIa IIb III
Beta blockers should be continued during and after
hospitalization for all patients with STEMI and with no
contraindications to their use.
*Risk factors for cardiogenic shock (the greater the number of risk factors present, the higher the
risk of developing cardiogenic shock) are age >70 years, systolic BP <120 mm Hg, sinus
tachycardia >110 bpm or heart rate <60 bpm, and increased time since onset of symptoms of
STEMI.
Antihypertensive Agents
Beta-Adrenergic Blockers
(Beta Blockers)
•
•
•
•
For patients with acute MI, beta blocker therapy reduces
infarct size and early mortality when started early and
lowers the risk of death when continued long term
Decreased oxygen demand due to the reductions in HR,
BP and contractility, and the consequent relief of CPReduced Cardiac Output!
Decreased risk of v-fib; RRR in sudden cardiac death
(30-47%)
Reduction in remodeling and improvement in left
ventricular function; dependent on infarct size and time
to treatment
Slowing of yearly rate of progression of coronary
atherosclerosis in patients with or without MI
Beta-Adrenergic Blockers
(Beta Blockers)
Cardio selective - Preferred - acts mainly on Beta-1
receptors (heart)
 Atenolol , Metoprolol, Bisoprolol,
Nonselective - inhibits Beta-1 (heart) & Beta-2
(bronchial) receptors
- HR slows & BP decreases
- Bronchoconstriction occurs
*Use cautiously in clients w/ pulmonary history*
 Carvedilol, Labetalol, Nadolol, Propranolol, Sotalol,
Timolol, Pindolol
 Side effects: fatigue, weakness, depression,
impotence, bradycardia
Renin-Angiotensin-Aldosterone
System Inhibitors
I IIa IIb III
An ACE inhibitor should be administered within the first 24 hours
to all patients with STEMI with anterior location, HF, or EF less
than or equal to 0.40, unless contraindicated.
I IIa IIb III
An ARB should be given to patients with STEMI who have
indications for but are intolerant of ACE inhibitors.
Antihypertensive Agents
Angiotensin-Converting Enzyme Inhibitors
(ACE Inhibitors)
• Prevent production of angiotensin II, a
potent vasoconstrictor which
stimulates aldosterone production. This
results in systemic vasodilation,
decrease preload and afterload,
decreased BP, and prevention of overt
HF after MI
A-II blockers - block
angiotensin II from
receptors in blood
vessels, adrenals, and all
other tissues.
ACE inhibitors inhibit the
enzyme necessary for
the conversion of A-I to
A-II
Antihypertensive Agents
Angiotensin II Receptor Antagonists (Blockers)
(ARBs)
• Prevent production of angiotensin II, a
potent vasoconstrictor which
stimulates aldosterone production. This
results in systemic vasodilation,
decrease preload and afterload,
decreased BP, and prevention of overt
HF after MI
ACEIs and ARBs
• ACEIs*: lisinopril, captopril, benazepril,
enalapril, fosinopril, quinapril,ramipril
• ARBS**: losartan, Diovan, Avapro,
Micardis, Atacand, Benicar
Side effects: cough*, hypotension, loss of
taste perception, proteinuria,
headache** and dizziness**
JNC VII Lifestyle Modifications for BP
Control
Modification
Recommendation
Approximate SBP
Reduction Range
Weight reduction
Maintain normal body weight
(BMI=18.5-24.9)
5-20 mmHg/10 kg weight
lost
Diet rich in fruits, vegetables, low fat
dairy and reduced in fat
8-14 mmHg
Restrict sodium
intake
<2.4 grams of sodium per day
2-8 mmHg
Physical activity
Regular aerobic exercise for at least
30 minutes on most days of the week
4-9 mmHg
Moderate alcohol
consumption
<2 drinks/day for men and <1
drink/day for women
2-4 mmHg
Adopt DASH
eating plan
BMI=Body mass index, SBP=Systolic blood pressure
Chobanian AV et al. JAMA. 2003;289:2560-2572
Risk Factor Modification
ABCDE’s
•
•
•
•
•
Antiplatelets & Anticoagulation
Blood Pressure Management
Cholesterol & Cessation of Smoking
Diet
Education & Exercise
Lipid Management Goal
I IIa IIb III
LDL-C should be less than 100 mg/dL
I IIa IIb III
Further reduction to LDL-C to < 70 mg/dL is
reasonable
If TG >200 mg/dL, non-HDL-C should be < 130 mg/dL*
*Non-HDL-C = total cholesterol minus HDL-C
Relative Risk for Coronary
Heart Disease (Log Scale)
CHD Risk According to LDL-C Level
3.7
2.9
2.2
1.7
1.3
1.0
40
70
100
130
160
LDL-Cholesterol (mg/dL)
CHD=Coronary heart disease, LDL-C=Lowdensity lipoprotein cholesterol
Grundy S et al. Circulation 2004;110:22739
190
Lipid Management
I IIa IIb III
High-intensity statin therapy should be initiated or continued in all
patients with STEMI and no contraindications to its use.
I IIa IIb III
It is reasonable to obtain a fasting lipid profile in patients with
STEMI, preferably within 24 hours of presentation.
Therapies to Lower LDL-C
Class
Drug(s)
3-Hydroxy-3-Methylglutaryl Coenzyme A
(HMG-CoA) reductase inhibitors [Statins]
Atorvastatin (Lipitor)
Fluvastatin (Lescol XL)
Lovastatin (generic and Mevacor)
Pravastatin (Pravachol)
Rosuvastatin (Crestor)
Simvastatin (Zocor)
Bile acid sequestrants
Cholesterol absorption inhibitor
Nicotinic acid
Dietary Adjuncts
Cholestyramine (generic and Questran)
Colesevelam (Welchol)
Colestipol (Colestid)
Ezetimibe (Zetia)
Niacin
Soluble fiber
Soy protein
Stanol esters
Lipid Management
Pharmacotherapy
TC
LDL
HDL
TG
Patient
tolerability
 19-37%
 25-50%
4-12%
 14-29%
Good
 13%
18%
1%
 9%
Good
Bile acid
sequestrants
7-10%
10-18%
3%
Neutral or
Poor
Nicotinic acid
 10-20%
 10-20%
14-35%
 30-70%
Reasonable
to Poor
19%
4-21%
11-13%
30%
Good
Therapy
Statins*
Ezetimibe
Fibrates
HDL-C=High-density lipoprotein cholesterol, LDL-C=Low-density lipoprotein cholesterol,
TC=Total cholesterol, TG=Triglycerides
*Daily dose of 40mg of each drug, excluding rosuvastatin.
Lipid Lowering Agents
HMG-CoA Reductase Inhibitors
(Statins)
• The beneficial effects of statins are the result of
their capacity to reduce cholesterol biosynthesis,
mainly in the liver, by inhibiting HMG-CoA
reductase.
• Statins have anti-atherosclerotic effects, that
positively correlate with the percent decrease in
LDL cholesterol.
• Statins significantly reduce the incidence of
coronary events, both in primary and secondary
prevention, and are the most effective
hypolipidemic medications in reducing the rate
of mortality in coronary patients.
The Role of Lipoproteins in Atherogenesis
HDL
High plasma
LDL
Endothelial
injury
LDL
+
VLDL
LDL infiltration
into intima
Adherence
of platelets
Liver
Cholesterol
excreted
LCAT
APO-A1
Oxidative
modification
of LDL
+
Macrophages
Foam cells
Fatty streak
APO-A1=Apolipoprotein A1, HDL=High density
lipoprotein, LCAT=Lecithin cholesterol
acyltransferase, LDL=Low density lipoprotein,
PDGF=Platelet-derived growth factor, VLDL=Very
Other
growth
factors
Release
of PDGF
Advanced
fibrocalcific
lesion
Statin equivalent dosages
% LDL
reduction
(approx.)
Atorvastatin
Fluvastatin
Lovastatin
Pravastatin
Rosuvastatin Simvastatin
10–20%
20–30%
30–40%
40–45%
–
–
10 mg
20 mg
20 mg
40 mg
80 mg
–
10 mg
20 mg
40 mg
80 mg
10 mg
20 mg
40 mg
80 mg
–
–
5 mg
5–10 mg
5 mg
10 mg
20 mg
40 mg
46–50%
40 mg
–
–
–
10–20 mg
80 mg*
50–55%
56–60%
80 mg
–
–
–
–
–
–
–
20 mg
40 mg
–
–
* 80-mg dose no longer recommended due to increased risk of rhabdomyolysis
Starting dose
Starting dose 10–20 mg
20 mg
10–20 mg
40 mg
If higher LDL
reduction
goal
40 mg if >45% 40 mg if >25% 20 mg if >20% --
Optimal
timing
Anytime
Evening
With evening
Anytime
meals
10 mg;
5 mg if
20 mg
hypothyroid,
>65 yo, Asian
20 mg if LDL
40 mg if >45%
>190 mg/dL (
Anytime
Evening
Smoking
Independent Risk Factor for CAD
60% of Smokers Do Not Believe this
Incidence of MI is 3-6x increased
Patients with prior CAS have Increased
risk of Death, Sudden Death, and
Reinfarction
• Pathogenesis—  LDL +  TG +  HDL
•
•
•
•
– Impaired Endothelial Function—Dose
Related
– Enhanced Prothrombotic State
Mediators
• Nicotine—Sympathetic Neural
Stimulation ( BP + HR +  O2
Demand increases ischemia)
• CO—binds to Hb and Increases
Ischemia, Ventricular Dysfunction
• Oxygen Free Radicals—Atherosclerosis
development
Post-PCI—Smoking
•  Death—1.75x 
• Q wave MI—2x 
• 50% Decreased Reinfarction, Sudden
Death & Mortality if Patients Quit
Cigarette Smoking Recommendations
Goal: Complete Cessation and No Exposure
to Environmental Tobacco Smoke
•Ask about tobacco use status at every visit.
•Advise every tobacco user to quit.
•Assess the tobacco user’s willingness to quit.
I IIa IIb III
•Assist by counseling and developing a plan for
quitting.
•Arrange follow-up, referral to special programs,
or pharmacotherapy (including nicotine
replacement and bupropion.
•Urge avoidance of exposure to environmental
tobacco smoke at work and home.
Comparison of Nicotine Replacement Products
Availability
NRT Form
Flexible
Dosing
Min/Max Dose
Time To Onset
Oral
Delivery
Primary Side
Effects
Generic
Form
Available
Nicotine
Patch
Over-the-Counter
No
1 daily
1-3 hours
No
Topical skin rash
Yes
Nicotine
Gum
Over-the-Counter
Yes
9-20 daily
7-10 mins
Yes
mouth/throat
soreness
No
Nicotine
Lozenge
Over-the-Counter
Yes
9-20 daily
7-10 mins
Yes
hiccups; heartburn
No
Nicotine
Inhaler
Prescription
Yes
6-16 daily
5 mins
Yes
cough; throat
irritation
No
Nasal
Spray
Prescription
Yes
13-20 daily
10-15
mins
No
nose/throat
irritation;
runny nose
No
(Adapted from Schmitz J., Henningfield J, Jarvik M, "Pharmacologic Therapies for Nicotine Dependence." In Principles for Addiction Medicine,
Non-Nicotine Pill - Zyban
• Bupropion hydrochloride (Zyban®) was
approved in 1997 to help smokers quit. The
drug, available by prescription only, is also
sold as an antidepressant under the name
Wellbutrin, Wellbutrin SR, Budeprion SR..
• Common side effects include insomnia, dry
mouth and dizziness.
• Treatment with bupropion begins while the
user is still smoking, one week prior to the
quit date. Treatment is then continued for 7
to 12 weeks. Length of treatment is
individualized.
Chantix®
• The newest prescription drug Chantix, Varenicline
tartrate, is only the second nicotine-free smokingcessation drug to gain FDA approval. The active
ingredient varenicline works in two ways -- by
cutting the pleasure of smoking and reducing the
withdrawal symptoms that lead smokers to light up
again and again.
• The tablet will be taken twice-daily for 12 weeks, a
period that can be doubled in patients who
successfully quit to increase the likelihood they
remain smoke-free.
• The most common adverse side effects
include: nausea, headache, vomiting, gas,
insomnia, abnormal dreams, and a change in taste
perception.
Risk Factor Modification
ABCDE’s
•
•
•
•
•
Antiplatelets & Anticoagulation
Blood Pressure Management
Cholesterol & Cessation of Smoking
Diet
Education & Exercise
Exercise Evidence: Mortality
Risk
Observational study of self-reported physical activity in 772 men with
established coronary heart disease
Light or moderate exercise is associated with lower risk
Wannamethee SG et al. Circulation 2000;102:1358-1363
Post hospitalization Plan of Care
I IIa IIb III
Post hospital systems of care designed to prevent hospital
readmissions should be used to facilitate the transition to
effective, coordinated outpatient care for all patients with STEMI.
I IIa IIb III
Exercise-based cardiac rehabilitation/secondary prevention
programs are recommended for patients with STEMI.
Post hospitalization Plan of Care
I IIa IIb III
I IIa IIb III
A clear, detailed, and evidence-based plan of care that promotes
medication adherence, timely follow-up with the healthcare team,
appropriate dietary and physical activities, and compliance with
interventions for secondary prevention should be provided to
patients with STEMI.
Encouragement and advice to stop smoking and to avoid
secondhand smoke should be provided to patients with STEMI.
Questions