presenting faculty : tomas villanueva, do, mba, facpe, sfhm
DESCRIPTION
Presenting Faculty : Tomas Villanueva, DO, MBA, FACPE, SFHM Clinical Assistant Professor of Medicine College of Osteopathic Medicine Nova Southeastern University Medical Director, Hospital Medicine Program Baptist Health System of Miami Miami, FL - PowerPoint PPT PresentationTRANSCRIPT
Presenting Faculty:
Tomas Villanueva, DO, MBA, FACPE, SFHMClinical Assistant Professor of Medicine
College of Osteopathic MedicineNova Southeastern University
Medical Director, Hospital Medicine ProgramBaptist Health System of Miami
Miami, FL
Dr. Villanueva has disclosed that he is a consulting editor for Hospital Medicine Program Management and a reviewer for Hospital Medicine. He is also on the
speakers’ bureaus for American Regent, AstraZeneca, Forest, Novo Nordisk, and Pfizer.
Pre-test
67 year old man with history of DM and GI bleed six months ago is admitted with NSTE-ACS. Initial ECG showed anterolateral ST depressions and troponin levels rose to 1.3. He undergoes stenting of the LAD with a drug-eluting stent (DES). He is discharged to your care for further management.
What is the most appropriate daily dose of aspirin to treat him with long-term?
25%
25%
25%
25%
Countdown
10
A. 81 mg QDB. 325 mg (enteric coated) QDC. 325 mg BID (to better prevent stent thrombosis)D. It doesn’t matter
How long should his P2Y12 inhibitor therapy (clopidogrel, ticagrelor, or prasugrel) be continued?
0%
0%
0%
0%
A. One monthB. 3-6 monthsC. At least 12 monthsD. It depends on which P2Y12 inhibitor he was
placed on
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10
Should the patient be placed on a PPI?
25%
25%
25%
25%
Countdown
10
A. It dependsB. Yes C. NoD. Maybe
Pathophysiology of Plaque Rupture and Acute Coronary Syndromes
Coronary Atherosclerotic Plaque
• Coronary artery smooth muscle thickening
• Foam cells accumulate in smooth muscle
• Core of extracellular lipid accumulates
Plaque Core
RupturedVulnerable
FibrousCap
Thrombus
Ruptured Vulnerable Plaque with Thrombus Formation
Plaque Rupture with Coronary Thrombus
Platelet Aggregation
Adhesion1
Platelets
LipidCore
CollagenGP la/lla Bind
von WillebrandFactor/GP lb Bind
Activation2Thrombin
ADP
5 HT
TXA2
Aggregation3
FibrinogenActivatedGP llb/llla
Platelet Plug4
Schafer AI. Am J Med. 1996.
Platelet Cascade in ACS
Mortality in the Global Registry of Acute Coronary Events (GRACE)
16
12
8
4
00 30 60 90 120 150 180
% M
orta
lity
DaysFox KA, et al. BMJ. 2006;
Goldberg RJ, et al. Am J Cardiol. 2004.
STEMI
NSTEMI
UA
Mortality fromD/C to six monthsSTEMI – 4.8%NSTEMI – 6.2%Unstable – 3.6%
N=43,810
Aspirin for ACS and Secondary Prevention
17.1
6.5*
Placebo ASA0
5
10
15
20
Patie
nts (
%)
Unstable Angina
25.0
11.0*
ASA0
10
20
303.3
1.9*
ASA0
1
2
3
4
11.8
9.4*
ASA0
5
10
15
Acute MIP<.0001
Death or MIP=.001
ReocclusionP=.012
MIP<.001
Vascular Death
N= 397 399 513 419 8,587 8,600 8,587 8,600
MI=myocardial infarctionASA=acetylsalicylic acidRISC=Research on Instability in Coronary Artery Disease
Placebo Placebo Placebo
RISC Group. Lancet. 1990;Roux S, et al. J Am Coll Cardiol. 1992; ISIS-2. Lancet. 1988.
Aspirin in Acute Coronary Syndromes (ACS)
Antithrombotic Trialists Collaboration. Br Med J. 2002.
Chronic ASA Doses and Vascular Events in High Risk Patients
ASA dose (range 75-325 mg)
0
1.0
2.0
3.0
4.0
5.0
Inci
denc
e of
Maj
or
Blee
ding
(%)
1.9%
3.0% 2.8%
3.4%3.7%
4.9%
101–199 mg (N=3,109)
≥200 mg (N=4,110)
≤100 mg (N=5,320)
ASA + Placebo ASA + Clopidogrel
Peters RJ, et al. Circulation. 2003.
Relationship Between Major Bleeding and ASA Dose in ACS Patients
Post-hoc Analysis from CURE
• UA/NSTEMI (2011 Focused Update):1
• 75-162 mg indefinitely• STEMI (2004 Guideline):2
• 75-162 mg indefinitely• Secondary Prevention (2011 Update):3
• 75-162 mg indefinitely• PCI (2011 Guideline):4
• Aspirin indefinitely (class I; LOE A)• Reasonable to use 81 mg/day in preference to higher
maintenance doses (class IIa; LOE B)
1Wright RS, et al. Circulation. 2011;
2Antman EM, et al. J Am Coll Cardiol. 2004;3Smith S, et al. J Am Coll Cardiol. 2011;
4Levine GN. J Am Coll Cardiol. 2011.
Aspirin Dosing After ACS/PCI: Current ACCF/AHA Recommendations
Clopidogrel After NSTE-ACS
Yusuf S, et al. N Engl J Med. 2001.
20% RRRP=.00009
2
4
6
8
10
12
14
% W
ith E
vent
Clopidogrel + Aspirin
3 6 9
Placebo + Aspirin
Follow-up (Months)0 12
11.4%
9.3%
CURE Trial: Primary Composite Endpoint (MI/CVA/CV Death)
at 12 Months in Patients with NSTE-ACS
Clopidogrel For Primary and Secondary Prevention
CHARISMA Trial Design(Clopidogrel in Addition to Aspirin in Patients Without Recent ACS)
Clopidogrel 75 mg/day(N=7,802)
Placebo 1 tablet/day
(N=7,801)1-month visit
Final visit (Fixed study
end date)
Patients age ≥45 years at high risk of atherothrombotic events*
R Double-blind treatment up to 1040 primary efficacy events (CV death, MI or CVA)
Low dose ASA 75-162 mg/day
Low dose ASA 75-162 mg/day
(N=15,603)
Visits every 6 months3-month visit
Bhatt DL, et al. Am Heart J. 2004.
*Documented CAD, CVD, symptomatic PAD or >=2 CRF
CHARISMA: Overall Population: Primary Efficacy Outcome (MI, Stroke, or CV Death)†
† First Occurrence of MI (fatal or non-fatal), stroke (fatal or non-fatal), or cardiovascular death*All patients received ASA 75-162 mg/day§The number of patients followed beyond 30 months decreases rapidly to zero and there are only 21 primary efficacy events that occurred beyond this time (13 clopidogrel and 8 placebo)
Placebo + ASA*7.3%
Clopidogrel + ASA*6.8%
RRR: 7.1% [95% CI: -4.5%, 17.5%]P=.22
Months since randomization§
0
2
4
6
8
0 6 12 18 24 30
Cum
ulati
ve e
vent
rate
(%)
Bhatt DL, et al. N Engl J Med. 2006.
Population RR (95% CI) P
value
Qualifying CAD, CVD or PAD 0.88 (0.77, 0.998) .046(N=12,153)
Multiple Risk Factors 1.20 (0.91, 1.59) .20 (N=3,284)
Overall Population* 0.93 (0.83, 1.05) .22 (N=15,603)
CHARISMA Primary Efficacy Results (MI/Stroke/CV Death) by Pre-Specified Entry Category
0.6 0.8 1.41.2Clopidogrel Better Placebo Better
1.60.4
*A statistical test for interaction showed marginally significant heterogeneity (P=.045) in treatment response for these pre-specified subgroups of patients
Bhatt DL, et al. N Engl J Med. 2006.
10
8
6
4
2
0
CHARISMA – Prior MI
0 6 12 18 24 30
HR=0.774 (95% CI [0.613–0.978])P=.031
N=3,846
Prim
ary
Out
com
e Ev
ent R
ate
(%)
Months Since Randomization
8.3%
6.6%
Placebo + ASAClopidogrel + ASA
Bhatt DL, et al. J Am Coll Cardiol. 2007.
Clopidogrel should be considered in a non-diabetic patient with high risk for atherosclerosis but has not had an episode of ACS.
0%
0%
A. TrueB. False
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10
P2Y12 Inhibitor Therapy After Stenting
Lesion crossed with guidewire
Deployed stent In artery
Lesion dilated with balloon
Stent alignedin lesion
Coronary Stenting
Coronary Stenting
Pre-PTCA Post-Balloon Post-Stent
CREDO: One Year Primary OutcomeStable CAD and ACS Patients Rx with Bare Metal Stents (BMS)
Months0 3 6 9 12
8.5%
11.5%
0
5
15
10
ClopidogrelN=1,053
PlaceboN=1063
Deat
h, M
I, or
Str
oke
27% RRRP=.02
Steinhubl SR, et al. JAMA. 2002.
Continued Risk of Drug Eluting Stent (DES) Thrombosis
DES Stent Thrombosis In The Bern/Rotterdam Two Center Experience
Series10
1
2
3
4
0 365 7301,095
Sten
t Thr
ombo
sis (%
)
Days After Stenting
P. Wenaweser and P.W. Serruys, ESC 2006. (Slide courtesy of Roxana Mehran, Columbia University)
Paclitaxel DES
Sirolimus DES
0
1
3
2
4
Newer P2Y12 Inhibitors ∙ Prasugrel Ticagrelor∙
Bhatt DL. N Engl J Med. 2009;van Giezen JJ. Eur Heart J Suppl. 2008.
• Thienopyridine• “Irreversible” platelet
inhibition• Rapidly metabolized
prodrug• Rapid onset of action• Greater and more
reliable platelet inhibition than clopidogrel
Prasugrel
mean ± SEM 20 μM ADP
Inhi
bitio
n of
Pl
atel
et A
ggre
gatio
n (%
)
0
20
40
60
80
100
Loading Dose Maintenance Doses
Time Hours Days
0.25 0.5 1 2 4 6 24 3 4 5 6 7 8 90
Clop 300 mg
Clop 75 mg
††
!
!
† §
† P<.001 vs. Clop 300!P<.05 vs. Clop 300
§P<.05 vs. Clop 300/75
Clop 600 mg
Clop 75 mg
*
*
** * *
* * * * * * *
*P<.001 vs. Clop 300 mg or 600 mg LD
Pras 60 mg
Pras 10 mg
Wiviott SD, et al. Circulation. 2007.
PRINCIPLE-TIMI 44Prasugrel vs. Clopidogrel
Double-blind
ACS (STEMI or UA/NSTEMI) and Planned PCI
ASA
PRASUGREL60 mg LD/10 mg MD
CLOPIDOGREL300 mg LD/75 mg MD
1o endpoint: CV death, MI, Stroke2o endpoints: CV death, MI, Stroke, Rehospitalization for Recurrent Ischemia
CV death, MI, UTVR Stent Thrombosis (ARC definite/prob.) Safety endpoints: TIMI major bleeds, Life-threatening bleedsKey Substudies: Pharmacokinetic, Genomic
Median duration of therapy: 12 months
N=13,600
Wiviott SD, et al. N Engl J Med. 2007.
TRITON-TIMI 38: Study Design
LD=loading dose; MD=maintenance dose
0
2
4
6
8
0 1 2 3
1
0 30 60 90 180 270 360 450
HR 0.82P=.01
HR 0.80P=.003
5.6
4.7
6.9
5.6
Days
Prim
ary
Endp
oint
(%)
(CV
deat
h, M
I, CV
A)
Prasugrel
Clopidogrel
Prasugrel
Clopidogrel
Loading Dose Maintenance Dose
Wiviott SD, et al. N Engl J Med. 2007.
TRITON-TIMI 38 Timing of Benefit: Landmark Analysis
0
1
2
2.5
0 30 60 90 180 270 360 450
HR 0.48P<.0001
Prasugrel
Clopidogrel 2.4(142)
NNT=77
1.1 (68)
Days
Defin
ite &
Pro
babl
e St
ent
Thro
mbo
sis (%
)
Any Stent at Index PCI N=12,844
Wiviott SD, et al. N Engl J Med. 2007.
TRITON-TIMI 38: Definite and Probable Stent Thrombosis
TIMI Major Bleeds
Life Threatening Nonfatal Fatal ICH0
2
4
1.8
0.9 0.9
0.10.3
2.4
1.41.1
0.4 0.3
% E
vent
s
ARD 0.6%HR 1.32
Clopidogrel Prasugrel
ARD 0.5%HR 1.52
ARD 0.2% ARD 0%ARD 0.3%
P=.03
P=.01P=NS
P=.002 P=NS
Wiviott SD, et al. N Engl J Med. 2007.
ICH in Pts with Prior Stroke/TIA
(N=518)Clopidogrel 0 (0%) Prasugrel 6 (2.3%)
P=.02
TRITON-TIMI 38: Bleeding Events
ARD=absolute risk difference
Medically Managed UA/NSTEMI Patients
Clopidogrel*
75 mg MD
Prasugrel*
5 or 10 mg MD
Minimum Rx Duration: 6 months; Maximum Rx Duration: 30 months
Primary Efficacy Endpoint: CV Death, MI, Stroke
Randomization Stratified by:Age, Country, Prior Clopidogrel Treatment(Primary analysis cohort — Age <75 years)
Clopidogrel*300 mg LD
+75 mg MD
Prasugrel*30 mg LD
+5 or 10 mg MD
Medical Management Decision ≤72 hrs(No prior clopidogrel given) – 4% of total
Medical Management Decision ≤ 10 days(Clopidogrel started ≤72 hrs in-hospital OR
on chronic clopidogrel) – 96% of total
*All patients were on aspirin and low-dose aspirin (<100 mg) was strongly recommended. For patients <60 kg or ≥75 years, 5 mg MD of prasugrel was given
Median Time to Enrollment=4.5 Days
Adapted from Chin CT, et al. Am Heart J. 2010.
TRILOGY ACS Study Design
HR: 0.91P=.21 (NS)
Interaction P=.07
20
10
15
5
00 180 360 540 720 900
Roe MT, et al. N Engl J Med. 2012.
Prasugrel: 3,620 3,248 2,359 1,611 953 389Clopidogrel: 3,623 3,244 2,390 1,596 946 399
No. at risk Time, days
ClopidogrelPrasugrel
16.0%13.9%
*Primary endpoint=CV death, nonfatal MI, nonfatal stroke **Primary analysis excludes age >75 yrs
Prim
ary
Effica
cy E
ndpo
int (
%)*
*
HR ≤1Year: 0.99(0.84, 1.16)
HR >1 Year: 0.72(0.54, 0.97)
TRILOGY ACS: Primary Efficacy Endpoint*
Bhatt DL. Nature Reviews Cardiology. 2009;van Giezen JJ. Eur Heart J Suppl. 2008.
•Non-thienopyridine
•“Reversible” binding of P2Y12 receptor
•Active drug
•Quick onset of action
•Greater degree of and more reliable platelet inhibition than clopidogrel
Ticagrelor
Ticagrelor 90 mgTicagrelor 180 mgTicagrelor 270 mg
Clopidogrel 300 mg
0 2 4 6 8 10 120
25
50
75
100
Time Post Dose (Hours)
IPA,
% (m
ean
± SE
M)
Keeley EC, et al. Lancet. 2006.
Inhibition of Platelet Aggregation (IPA)
DISPERSE 2Comparative Effects on Platelet Aggregation of Ticagrelor vs. Clopidogrel
Primary endpoint: CV death + MI + Stroke Primary safety endpoint: Total major bleeding
6-12-month exposure
ClopidogrelIf pretreated, no additional loading dose;if naive, standard 300 mg loading dose,
then 75 mg QD maintenance;(additional 300 mg allowed pre-PCI)
Ticagrelor180 mg loading dose, then90 mg BID maintenance;
(additional 90 mg pre-PCI)
NSTEMI-ACS (moderate-to-high risk), STEMI (if primary PCI)Clopidogrel-treated or -naive;
randomized within 24 hours of index event (N=18,624)
Wallentin L, et al. N Engl J Med. 2009.
PLATO Study Design
*Composite of CV death, MI, or stroke
No. at risk
ClopidogrelTicagrelor
9,2919,333
8,5218,628
8,3628,460
8,124
Days after Randomisation
6,6506,743
5,0965,161
4,0474,147
0 60 120 180 240 300 360
121110
9876543210
13Cu
mul
ative
inci
denc
e (%
)
9.8%
11.7%
8,219
HR 0.84 (95% CI 0.77-0.92)P=.0003
Clopidogrel
Ticagrelor
Wallentin L, et al. N Engl J Med. 2009.
PLATO: Time to Primary Efficacy Endpoint*
Days after randomisation
0 60 120 180 240 300 360
6
5
4
3
2
1
0
7
Cum
ulati
ve in
cide
nce
(%) Clopidogrel
Ticagrelor
5.8
6.9
HR 0.84 (95% CI 0.75-0.95)P=.005
0 60 120 180 240 300 360
6
4
3
2
1
0
Clopidogrel
Ticagrelor4.0
5.1
HR 0.79 (95% CI 0.69-0.91) P=.001
7
5
Days after randomisation
Myocardial infarction Cardiovascular death
Cum
ulati
ve in
cide
nce
(%)
Wallentin L, et al. N Engl J Med. 2009.
PLATO: Secondary Efficacy Endpoints
Estim
ated
Rat
e (%
per
yea
r)
Wallentin L, et al. N Engl J Med. 2009.
P=.026
P=.025
P=.32 (NS)9
Non-CABGPLATO major
bleeding
87
6
54
32
10 Non-CABG
TIMI major bleeding
CABGPLATO major
bleeding
CABG TIMI major
bleeding
4.53.8
2.82.2
7.47.9
5.35.8
P=.32 (NS)
P=.57 (NS)
P=.43 (NS)
0PLATO criteria
major bleeding
1
2
3
4
5
6
7
8
910
12
11
13
TIMI criteria major
bleeding
11.611.2
7.9 7.7
Ticagrelor Clopidogrel
PLATO: Overall, Non-CABG and CABG-related Major Bleeding
*Evaluated in patients with any stent during the study
Wallentin L, et al. N Engl J Med. 2009.
Stent Thrombosis, %
Ticagrelor(N=5,640)
Clopidogrel(N=5,649) HR (95% CI) P Value
Definite 71 (1.3%) 106 (1.9%) 0.67 (0.52-0.91) .009
Probable of definite 118 (2.1%) 158 (2.8%) 0.75 (0.59-
0.95) .02
Possible, probable, or definite
155 (2.8%) 202 (3.6%) 0.77 (0.62-0.95) .01
PLATO: Stent Thrombosis*
James SK, et al. BMJ. 2011.
0
4
8
12
16
20
0 60 120 180 240 300 360
Days after Randomization
Card
iova
scul
ar d
eath
, MI,
or S
trok
e (%
)
14.3%
12.0%HR 0.85P=.04
•N=5,216 (1/4 total study population, 1/3 NSTE-ACS population)•In-hospital procedures: cath 41.9%; PCI 20.4%; CABG 4.0%•By final follow-up: revascularization 40% (PCI only 72.6%; CABG only 25.8%; both 1.6%)
Clopidogrel
Ticagrelor
PLATO: Initial Non-Invasive Strategy Subgroup
0
2
4
6
8
10
Days after Randomization
All-c
ause
Mor
talit
y (%
) 8.2%
6.1%
HR 0.75P=.01
0 60 120 180 240 300 360
James SK, et al. BMJ. 2011.
Ticagrelor
Clopidogrel
•N=5,216•In-hospital procedures: cath 41.9%; PCI 20.4%; CABG 4.0%•By final follow-up: revascularization 40% (PCI only 72.6%; CABG only 25.8%; both 1.6%)
PLATO: Initial Non-Invasive Strategy Subgroup
Clopidogrel Prasugrel Ticagrelor
Class Thienopyridine Thienopyridine Triazolopyrimidine
“Reversibility” Irreversible Irreversible Reversible
Activation Prodrug, limited by metabolism
Prodrug, not limited by metabolism Active drug
Onset of effect 2-4 hr 30 min 30 min
Duration of effect 3-10 days 5-10 days 3-4 days
Withdrawal before major elective surgery 5 days 7 days 5 days
Contraindications/Caveats
•600 mg loading dose (not FDA approved) provides faster, greater, and more reliable platelet inhibition•CYP2C19 *2 or *3 alleles are poor metabolizers and have reduced antiplatelet effects
•Contraindicated in patients with hx CVA/TIA•Generally not recommended in patients age >75 years (bleeding risk)•Increased bleeding risk if body weight <60 kg
•Concomitant ASA dose should be <100 mg•Contraindicated if severe hepatic impairment•Avoid use with strong CYP3A inhibitors* or CYP3A inducers**
Based in part from Hamm CW, et al. Eur Heart J. 2011, as well as drug PIs and study protocols.
*clarithromycin, ketoconazole, indinavir, itraconazole, etc. **rifampin, carbamazepine, dexamethasone, phenytoin, phenobarbital
Summary of P2Y12 Inhibitor Properties and Use
Which of the following features do prasugrel and ticagrelor NOT share?
0%
0%0%
0%
A. Platelet receptor targetB. Superiority over clopidogrel in preventing stent thrombosisC. Once-daily dosingD. No generic formulation available
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10
Patients on ticagrelor should be on a dose of aspirin under 100 mg per day.
0%
0%
A. TrueB. False
Countdown
10
Recommendation COR LOEEarly Invasive Strategy, Medium to High Risk Patients:
• Aspirin indefinitely I A
• P2Y12 inhibitor therapy (clopidogrel, ticagrelor, or prasugrel) in post-PCI patients at least 12 months I B
• If the risk of morbidity because of bleeding outweights the anticipated benefits afforded by P2Y12 receptor inhibitor therapy, earlier discontinuation should be considered
I C
Initial Conservative (noninvasive) Strategy
• Aspirin indefinitely I A
• P2Y12 inhibitor therapy (clopidogrel or ticagrelor) for up to 12 months I B
Jneid H, et al. J Am Coll Cardiol. 2012.
2012 ACCF/AHA Selected Recommendations for Antiplatelet Therapy in UA/NSTEMI
COR=class of recommendation; LOE=level of evidence; ACCF=American College of Cardiology Foundation; AHA=American Heart Association; GPI =glycoprotein IIb/IIIa Inhibitor
2011 ACCF/AHA/SCAI PCI Recommendations: P2Y12 Inhibitor Therapy with Coronary Stents
Recommendation COR LOEP2Y12 inhibitor therapy (clopidogrel, prasugrel, or ticagrelor for at least 12 months in patients receiving a stent (BMS or DES) during PCI for ACS I B
Clopidogrel for at least 12 months in patients treated with a DES for a non-ACS indication, if patients are not at high risk of bleeding I B
Clopidogrel for a minimum of 1 month and ideally up to 12 months in patients receiving a BMS for a non-ACS indication (unless the patient is at increased risk of bleeding; then it should be given for a minimum of two weeks)
I B
Earlier discontinuation (e.g., <12 months) of P2Y12 inhibitor therapy after stent implantation if the risk of morbidity from bleeding outweighs the anticipated benefit afforded by a recommended duration of P2Y12 inhibitor therapy
IIa C
Continuation of DAPT beyond 12 months in patients undergoing DES implantation IIb C
Levine GN, et al. J Am Coll Cardiol. 2011.
ESC Recommendations for P2Y12 Inhibitors in Patients with CKD
Clopidogrel Experience is limited in patients with severe renal impairment; use with caution
Prasugrel No dosage adjustment is necessary for patients with renal impairment; limited experience in ESRD
Ticagrelor No dose reduction is necessary for patient with renal impairment; limited experience in dialysis
Hamm CW, et al. Eur Heart J. 2011.
Prasugrel is NOT indicated for ACS patients that will undergo a PCI.
0%
0%
A. TrueB. False
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10
PPI Treatment With Dual Oral Antiplatelet Therapy (DAPT)
Bhatt DL, et al. N Engl J Med. 2010.
COGENT Trial – Effect of PPI on Composite GI Events
HR 0.34, 95% CI 0.18-0.63
Time (Days)
Prob
abili
ty o
f Fre
edom
fr
om P
rimar
y GI
End
poin
t
0 50 100 150 180 2000.00
0.90
1.00
Placebo
Omeprazole
P<.001 by the log-rank test
No. at RiskPlacebo 1,885 1,455 951 523 260 231Omeprazole 1,876 1,500 987 553 250 215
COGENT Trial – Effect of PPI on Composite Cardiovascular Events
HR 0.99, 95% CI 0.68-1.44
Time (Days)
Prob
abili
ty o
f Fre
edom
from
Pr
imar
y CV
End
poin
t
0 50 100 150 180 2000.00
0.90
1.00
Placebo
Omeprazole
P=.98 by the log-rank test
No. at RiskPlacebo 1,885 1,449 945 515 250 218Omeprazole 1,876 1,488 966 537 242 205
Bhatt DL, et al. N Engl J Med. 2010.
PPI Therapy and DAPT Recommendations Based on Risk of GI Bleeding
Recommendation COR LOE
PPI use for patients with history of prior GI bleeding who require DAPT I C
PPI use for patients with increased risk of GI bleeding (advanced age, concomitant use of warfarin, steroids, NSAIDs, H. pylori infection, etc.) who require DAPT
IIa C
Routine use of a PPI for patients at low risk of GI bleeding, who have much less potential to benefit from prophylactic therapy
III: No Benefit C
How Much of the Patient Are We Treating?
0.0002 m2
1,000 m2
=1/5,000,000Courtesy of Steven Steinhubl.
Established Therapies Are Consistently Underused in All Patient Types
CAD (N=40,258) Cerebrovasc Dis (N=18,843)
PAD (N=8,273) ≥3 Risk Factors (N=12,389)
0
10
20
30
40
50
60
1418 18
46
19
39
30
1924
4436
28
Antiplatelets Lipid-lowering Statin
Patie
nts N
ot R
ecei
ving
The
rapy
(%
of s
ubpo
pula
tion)
Bhatt DL, et al. JAMA. 2006.
Placebo-Controlled Mega-Trials of Statin Therapy in Primary and Secondary Prevention
WOSCOPS (
CAD death or n
o NFMI)
4S (total m
ortality
)
CARE (CAD death O
r NFMI)
LIPID
(total
morta
lity)
HPS (total m
ortality
or Vasc
Event)
GREACE (total m
ortality
)
ASCOTS-LL
P (NFMI +
Fatal CHD)
CARDS (MACCE)
0
10
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31% 30%24% 23%
28%
43%36% 37%
% R
educ
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in P
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• All patients hospitalized for CAD should have lipid profile obtained within 24 hours of admission• All patients with CAD should be screened
• Drug Rx can be started simultaneously with life-style changes
• CAD-equivalents include:• PVD, AAA, carotid disease• Diabetes• Multiple CRF conferring high risk of
developing CAD• Goal: LDL <100 mg/dL
NCEP ATP IIILatest Recommendations for Primary and Secondary Screening,
Prevention, and Therapy: Secondary Prevention
Grundy SM, et al. J Am Coll Cardiol. 2004.
NCEP ATP III Update
• Emphasized LDL <100 mg/dL is a “minimal goal of therapy” for secondary prevention
• Consider goal of <70 mg/dL in very high risk patients
• These patients are those with established CVD plus:• Multiple major risk factors (especially DM)• Severe and poorly controlled risk factors
(especially continued smoking)• Multiple risk factors of metabolic syndrome (TG
>200, etc.)• Patients with ACS
Grundy SM, et al. J Am Coll Cardiol. 2004.
Which of the following medical therapies is MOST effective at preventing stent thrombosis?
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A. StatinsB. Beta blockersC. ACEI-ARBD. Good glycemic control in diabetic patientsE. Dual antiplatelet therapyF. Good blood pressure control in hypertensive
patients
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10
Medication Adherence
Medication Adherence
National Transitions of Care Coalition. Available at: http://www.ntocc.org.
• One in three patients fail to fill their prescriptions• Approximately three of four Americans report they do not
consistently take their medications as directed• Sixty percent of patients cannot correctly name their medications and
up to 20% of patients take other people’s medications• Between 33 and 69 percent of medication-related hospital admissions
in the U.S. are due to poor adherence• Approximately one-fourth of all nursing home admissions are related
to improper self-administration of medications• In common chronic conditions such as diabetes and hypertension,
adherence rates average between 50-65 percent
Medication Adherence Decreases Over One Year
OA=oral anticoagulant
OMT=optimal medical therapy
Discharge1 Year
*P=.03**P<.001
% P
atien
ts
Study Design• Canadian
Survey• 1956 NSTEMI
patients prospectively followed
• Hospital and discharge data collected by chart review
• One-year adherence data collected by patient telephone interview
Bagnall AJ, et al. Circ Cardiovasc Qual Outcomes. 2010.
Reasons Medications Were Not UsedCanadian Survey
Conclusions• Physicians underestimated risk or were misinformed about guidelines• One third of EBT nonadherent patients had stopped their own treatment• Antiplatelet, β-blocker, and ACEI use declined during the year after discharge
Suggested solutions• Discharge contract signed by patient• Cardiac rehab and education
Bagnall AJ, et al. Circ Cardiovasc Qual Outcomes. 2010.
Predictors of Antiplatelet DiscontinuationOne-Year Follow-Up After DES Implantation
Ferreira-González I, et al. Circulation. 2010.
OR, odds ratio of discontinuation of antiplatelet therapy
Rehospitalizations: Medicare Fee-for-Service
Jencks FS, et al. N Engl J Med. 2009.
19.6%
34.0%
≤30 days ≤90 days
Summary Analysis
• 19.6% (nearly 1/5) were rehospitalized within 30 days
• 34% were rehospitalizedwithin 90 days
• 50.2% of those rehospitalized within 30 days after a medical discharge there was no bill for a visit to a physician office
• Analysis of Medicare Claims data from 2003-2004• Includes the 11,855,702 Medicare beneficiaries discharged from the hospital
Case Study
• Jose is a 66-year-old gentlemen with a h/o HTN and dyslipidemia, transferred to the tele floor from the ICU with the Dx of a STEMI and implantation of a drug-eluting stent (DES).
• The patient and his family were poor historians on admission and it is unclear whether his medical and medication history are accurate.
• Jose is anxious to “get out of here” and thinks this is “no big deal”.
Continuity of Care:
Key Information Exchange Between the Inpatient Team and the Primary Care Team
Pre-hospitalization and Hospitalization
• Medication reconciliation during pre-hospitalization may be complicated by the lack of a reliable source of medication history and should be re-evaluated 24 hours after the patient is admitted
• Contact with the PCP is appropriate during the hospital stay, and may offer valuable insight about issues related to discharge planning
• A particular challenge of ACS care is the extensive amount of complex information which must be shared quickly and accurately with all stakeholders
• The risk of miscommunication is real
Case Study, Continued…
• Jose’s PCP provided more information about his medical and medication history
• His father died of a heart attack at age 62
• Smoked on/off for several years and has been poorly compliant with diet, exercise, and taking statins
• He may not comprehend the seriousness of his heart disease and how secondary preventive measures may reduce his risk of further events
• His history of poor adherence raises concern that he will not persist with recommended ACS medications after discharge
Discharge and Post-Discharge
• Discharge is one of the most crucial transitions in care, with potential impact on patient outcomes post-discharge, including readmission
• The discharge summary is an obvious target for quality improvement, as it is the most common vehicle for sharing patient information with the PCP and other healthcare providers
Overcoming Barriers to Communication
• Poor literacy• Poor English proficiency• Poor understanding of medical jargon• Inadequate time with the clinician for questions and
answers• Poor cognition• Lack of communication between healthcare
professionals, specifically among physicians• Financial barriers to medication use
Case Study, The Finale…
• After verbally describing his discharge medications to Jose and his family, and providing written patient materials, you ask Jose to explain why his prescribed dual antiplatelet therapy is important
• A consult is requested from pharmacy for additional counseling
• Because you have been in direct contact with the PCP, you call now to express your concerns, in addition to noting Jose’s poor comprehension in the discharge summary
Transitioning the Patient With ACS From Inpatient to Primary Care
• Timely and accurate communication between the inpatient team and the PCP/PCHM is a vital component of a safe transition from inpatient to primary care.
• Communication directly impacts the continuity of care, patient outcomes, patient and caregiver satisfaction, and use of health care resources.
• The inpatient team should be cognizant of gaps in care related to how information is generated, recorded, and shared between the inpatient setting and primary care.
• The inpatient team responsibility for the patient does not end at the time of discharge. All reasonable effort should be done to assure that our patients, their caregivers and their outpatient providers are given all the tools necessary to complete and maintain the patient’s therapy.
Post-test
67 year old man with history of DM and GI bleed six months ago is admitted with NSTE-ACS. Initial ECG showed anterolateral ST depressions and troponin levels rose to 1.3. He undergoes stenting of the LAD with a drug-eluting stent (DES). He is discharged to your care for further management.
What is the most appropriate daily dose of aspirin to treat him with long-term?
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0% A. 81 mg QDB. 325 mg (enteric coated) QDC. 325 mg BID (to better prevent stent thrombosis)D. It doesn’t matter
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10
How long should his P2Y12 inhibitor therapy (clopidogrel, ticagrelor, or prasugrel) be continued?
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A. One monthB. 3-6 monthsC. At least 12 monthsD. It depends on which P2Y12 inhibitor he was
placed on
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10
Should the patient be placed on a PPI?
A. It dependsB. YesC. NoD. Maybe