presenting faculty : tomas villanueva, do, mba, facpe, sfhm

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

Countdown

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


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

Countdown

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


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


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


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


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

(%)


PLATO: Secondary Efficacy Endpoints

Estim

ated

Rat

e (%

per

yea

r)


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


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

Countdown

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

Countdown

10

PPI Treatment With Dual Oral Antiplatelet Therapy (DAPT)


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


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

20

30

40

50

31% 30%24% 23%

28%

43%36% 37%

% R

educ

tion

in P

rimar

y En

dpoi

nt

• 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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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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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

presenting faculty : tomas villanueva, do, mba, facpe, sfhm

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