Aderenza terapeutica: il fattore di rischio occulto · • 2002 anterior MI primary PCI (BMS) on...

Strategie di Prevenzione del Rischio CCV Globale

Bergamo 13 Novembre 2010

Roberta Rossini

USC Cardiologia Ospedali Riuniti di Bergamo

Aderenza terapeutica:

il fattore di rischio occulto

“I farmaci non funzionano nei pazienti che non li assumono”

C. Everett Koop, MD

Copyright ©2006 American Heart AssociationNewby, L. K. et al. Circulation 2006;113:203-212

Prevalence of use of aspirin, beta-blockers, lipid-lowering agents in patients with coronary artery disease

Impatto dell’interruzione precoce delle “evidence-based medical therapies” sulla prognosi clinica dopo

Infarto Miocardico Acuto: dati del Registro PREMIER

Impatto dellImpatto dell’’ interruzione precoce delle interruzione precoce delle ““ evidenceevidence--based medical based medical therapiestherapies”” sulla prognosi clinica dopo sulla prognosi clinica dopo

Infarto Miocardico Acuto: dati del Registro PREMIERInfarto Miocardico Acuto: dati del Registro PREMIER

Ho PM, et al.Arch Intern Med. 2006;166:1842-1847

HR

Interruzione dell’Aspirina

Interruzione dei Beta-bloccanti

Interruzione delle Statine

Riduzione della Mortalità Aumento della Mortalità

Copyright ©2010 American Heart AssociationBaroletti, S. et al. Circulation 2010;121:1455-1458

Causes of medication nonadherence

Khouzam RN, JACC 2 November 2010

A heart with 67 stents

Stent metallici (BMS)

Duplice antiaggregazione dopo

impianto di stent coronarici

Classe I

For post-PCI patients receiving a BMS, dual antipla telet therapy should be

given for a minimum of 1 month (level of Evidence: A)

ACC/AHA 2007 PCI Guidelines update

PCI Guidelines 2005

Classe IIn patients who have undergone PCI, clopidogrel 75 mg daily should be given for at least 3 months after sirolimus stent implantation, and 6 months after paclitaxel stent implantation, and ideally up to 12 months in patients who are not at high risk of bleeding.

(Level of Evidence: B)

PCI Guidelines UPDATE 2007Classe I

For all post-PCI stented patients receiving a DES, clopidogrel 75 mg daily should be given for at least 12 months if patients are not at high risk of bleeding.

(Level of Evidence: B)

Durata della duplice antiaggregazione dopo

impianto di stent medicati

ACC/AHA PCI Guidelines

Ospedali Riuniti di Bergamo

GP, male, 86 yrs old

• Dyslipidemia, COPD. Hb 11 g/dl

• 2002 anterior MI�primary PCI (BMS) on mid LAD

• June 2006 PCI on prox LAD (DES) for stable angina

• Oct 2006 Aspirin and Clopidogrel discontinuation due to melena and

subsequent gastroscopy

• Oct 2006 at 12:00 chest pain

• 16:20 at ER – Anterior AMI – Aspirin 250 mg i.v. –Heparin 5000 UI

GP, male, 86 yrs old

Ospedali Riuniti di Bergamo

• 16:30 cath lab arrival

• SBP 70 mmHg-Killip IV – Clopidogrel 300 mg

• 16:35 Coronary angiography starts

Pathology of DES in Humans

Temporal sequence of reendothelialization in BMS and DES



Joner et al., JACC 2006 48:193-202Joner et al., JACC 2006 48:193-202

68 DES > 30 days68 DES > 30 days

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 111516 2017Months

%

E

ndo

the

lializ

atio

n

DES

BMS

>400

20

40

60

80

100

1 2 3 4 5 6 7 8 9 111516 2017Months

%

E

ndo

the

lializ

atio

n

DES

BMS

>40

DESDES

BMSBMS

Premature Discontinuation of Antiplatelet Therapy as Predictor of ST

Premature Discontinuation of Antiplatelet Therapy as Predictor of ST

OR=89.8(29.9-270)

HR=19.2(5.6-65.5)

OR=4.8(2.0-11.1)

HR=13.7(4.0-46.7)

Odd

s/H

azar

dR

atio

Iakovou et alJAMA 2005

Park et alAm J CARD 2006

Kuchulakanti et alCirculation 2006

Airoldi et alCirculation 2006

We studied 1358 consecutive pts treated with DES and discharged on dual antiplatelet therapy with aspirin (100 mg/day) and clopidogrel (75 mg/day)

Clopidogrel was to be maintained for 12 months

Pts were followed-up for 32.4±11.3 months

86,4%

8,8% 4,8%

No discontinuation

Early discontinuation

Late discontinuation Rossini R et al. Am J Card 2011, in press

Discontinuation Causes:

� Surgery 34.5% � Bleeding 21%� Medical decision 17.6%� Dental interventions 7.6%� Economic/burocratic reasons 5.9% � Anticoagulant therapy 5.0%

Patients who discontinued antiplatelet therapy had a higher incidence of death, MACE and stent thrombosis

MACE

%

Discontinuation and Prognosis

Rossini R et al. Am J Card 2011, in press

Death, MACE or stent thrombosis and time of discontinuationDeath, MACE or stent thrombosis and time of discontinuation

%

P=0.10

P=0.02

P=0.008

P for trend = 0.004

P=0.10

P=0.02

P=0.008

P for trend = 0.004P=0.10

P=0.02

P=0.008

P for trend = 0.004


Any Discontinuation� history of prior stroke (OR=4.46, p=0.018) � statins at discharge (OR=0.35, p<0.001)� oral anticoagulants at discharge (OR=5.94, p<0.001)� in-hospital major bleeding(OR=7.69, p<0.001)� In-hospital minor bleeding (OR=2.17, p=0.028)

Predictors of Discontinuation

Early Discontinuation� in-hospital major bleeding (OR=9.00, p<0.001)� statins at discharge (OR=0.36, p<0.001)�oral anticoagulants at discharge (OR=8.21, p<0.001)

Late Discontinuation� history of prior stroke (OR=5.21, p<0.001)


Mehran RM et al. Eur Heart J 2009 June ; 30: 1457-1466

Influence of Major Bleeding and MI within 30 Days on Risk of Death Over 1 Year

Cox model adjusted for 36 baseline predictors, with MI and majorbleeding (non-CABG) as time-updated covariates


Of 13,819 enrolled pts, 524 (3.8%) died within 1 year

Myocardial infarction 3.1 (2.4-3.9) <0.001

Major bleeding 3.5 (2.7-4.4) <0.001

Blood transfusion 4.5 (3.4-5.9) <0.001

HR ± 95% CI P-valueHR (95% CI)

% 23,6

47,3

12,712,5

3,13,8

0

10

20

30

40

50

mortality MACE stentthrombosis

Major Bleeding and Long-Term Outcome

Major bleeding

No major bleeding

P<0.001

P<0.001

P=0.002

Rossini R, Musumeci G et al. ESC Congress 2010, Stockholm August 2010


63,6

11,5

0

10

20

30

40

50

60

70

80

90

100

Major Bleeding and Antiplatelet Discontinuation

Major bleeding

No major bleeding

%

Antiplatelet Discontinuation


Major bleeding

� Anemia at admission (OR =8.5 [3.7-19.2], p<0.001)�Oral anticoagulants at discharge (OR=8.4 [1.9-36.2], p=0.004);�Male sex (OR=0.39 [0.16-0.97], p=0.042);�Use of glycoprotein IIb/IIIa inhibitors (OR=2.5 [1.1-5.6], p=0.026)

Minor bleeding

� Oral anticoagulants at discharge (OR=6.2 [2.1-18.1], p=0.001);�Anaemia at admission (OR=2.7 [1.4-5.5], p=0.005);�Prior myocardial infarction (OR=2.0 [1.1-3.9], p=0.032);�Age (OR 1.03 [1.01-1.06], p=0.013)

Independent predictors of cumulativebleeding

Rossini R et al. J Am Coll Card 2010, abstr 2504. Atlanta March 2010

Discharge after acute coronary event

27.3% of patients discontinued statin therapy

during the 12-month follow-up

Median time to discontinuation 35 days (IQR 21–79)

2234 patients; 1385 men; mean age 72 years

IQR = interquartile range

100

90

80

70

0

Pat

ien

ts o

n t

reat

men

t (%

)

0 30 60 90 120 150 180 210 240 270 300 330 360

Time (days)

Discontinuation of statin therapy after ACSDiscontinuation of statin therapy after ACS

Colivicchi F, et al. Eur Heart J 2008;29 (Suppl. 1):68

Statin Discontinuation after MI and long-term MortalityUnited Kingdom General Practice Research Database (n=9939)

Statin Discontinuation after MI and long-term MortalityUnited Kingdom General Practice Research Database (n=9939)

Daskalopoulou S et al. Eur Heart J 2008 29(17): 2083-2091

Reported Side Effects

� Dyspepsia

� Fatigue

� Headache

� Myalgias

� Asymptomatic increase in liver enzymes

� Asymptomatic increase in total CK

“Too many pills”

CK = creatine kinase

Reported causes of discontinuation of statin therapy after an acute coronary event

Reported causes of discontinuation of statin therapy after an acute coronary event

Colivicchi F, et al. Eur Heart J 2008;29 (Suppl. 1):68

Conclusioni

La scarsa aderenza alla terapia rappresenta un fattore di rischio

occulto

E’ spesso legata ad una comunicazione inefficace o alla

mancanza di motivazione adeguata

L'aumentata complessità, e talvolta scarsa maneggevolezza,

della terapia farmacologica poco si concilia con una

ospedalizzazione sempre più breve, in cui il paziente non

raggiunge la piena consapevolezza della sua patologia

How much is too much?

� Clopidogrel is a prodrug. It requires the conversion by the liver primarily via CYP3A4 and CYP2C19 to an active metabolite

� PPIs are strong inhibitors of CYP2C19 activity

�� Clopidogrel is a prodrug. It requires the conversion by the liveClopidogrel is a prodrug. It requires the conversion by the liver r primarily via CYP3A4 and CYP2C19 to an active metaboliteprimarily via CYP3A4 and CYP2C19 to an active metabolite

�� PPIs are strong inhibitors of CYP2C19 activityPPIs are strong inhibitors of CYP2C19 activity

Clopidogrel and PPIs Clopidogrel and PPIs –– The OCLA studyThe OCLA study

-32.6

-43.3

-50-45-40-35-30-25-20-15-10-50

PR

I Var

iatio

n (%

)

Omeprazole (n=64)

Placebo (n=60)

PRI: Platelet Reactivity Index as measured by vasodilator stimulated phosphoprotein (VASP)

Gilard et al. J Am Coll Cardiol 2008;51:256-60

p<0.0001

MYOCARDIAL INFARCTION

31%

with PPIs

RR (95%CI)

Siller-Matula J Thromb Haemost, 2010 september 10

GASTROINTESTINAL BLEEDING

50%with PPIs

RR (95%CI)

Siller-Matula J Thromb Haemost, 2010 september 10

Days

Sur

viva

l Pro

babi

lity

0 30 60 90 120 150 180 210 240 270 300 330 360 390

0.90

0.92

0.94

0.96

0.98

1.00

Placebo

Treated

Survival Curves for PPI Treated vs PlaceboComposite Cardiovascular Events

Adjustment through Cox Proportional Hazards ModelAdjustment through Cox Proportional Hazards ModelAdjusted to Positive NSAID Use and Positive H. Pylori StatusAdjusted to Positive NSAID Use and Positive H. Pylori Status

HR = 1.0295% CI = 0.70; 1.51

The COGENT Trail. Bhatt D. et al. NEJM, october 6, 2010

HR = 0.5595% CI = 0.36; 0.85

p=0.007

Reduction of GI events by PPI

%

Long-term events

P=0.56

P=0.39

P=0.26

Rossini R et al. Eur Heart J 2010;30:741

%

Long-term events

P=0.518

P=0.974

P=1.00


%

One year Outcome: Clopidogrel and PPI in 1328 pts

P=0.46 P=0.62 P=0.67


Aspirin Sensitivity Reactions

Gollapude R; JAMA. 2004.292;:3017-3023

Aspirin Desensitization Protocol

Time (min) Aspirin dose (mg)

0 1

30 5

60 10

90 20

210 40

330 100

R. Rossini et al. Am J Cardiol 2008;101:786 –789

Aspirin Desensitization Results(N=52)

Aspirin Desensitization Results(N=52)

94,3

0

20

40

60

80

100

Procedural success

%

6,6

93,4

Pre-PCI desesitization

Post-PCI desesitization

%

%


82,7

0

20

40

60

80

100

Aspirin at FU

Results: Aspirin use and MACE at one yearResults: Aspirin use and MACE at one year

2 4 6 8 10 120

60

70

80

90

100

Freedom from MACE%

Months

92.3%

N = 4 TVR (PCI = 3 and CABG = 1)

%Stop 17,3%


Conclusioni

La terapia con statine è attualmente l’unica terapia farmacologica capace di rallentare la progressione della placca ateromasica

La terapia con statine ad alto dosaggio nei pazienti con ACS è sicura ed efficace determinando un beneficio precoce e prolungato rispetto alla terapia con statine a dose standard

L’interruzione prematura o la sostituzione terapeutica di statine ad alto dosaggio con agenti della stessa classe, ma con minore azione ipolipemizzante comporta un peggioramento della prognosi clinica, con aumento della morbilità e mortalitàcardiovascolare

L’interruzione prematura della tp antiaggregante si associa a prognosi sfavorevole ed èdeterminata soprattutto da sanguinamenti ed interventi chirurgici

I sanguinamenti, che si verificano sia in fase acuta che a lungo termine, condizionano sfavorevolmente la prognosi

Prima di scegliere la terapia antiaggregante e la strategia di rivascolarizzazione èimportante stratificare il rischio di prematura interruzione della tp antiaggregante, di sanguinamento e di procedura chirurgica a breve-medio termine

%


P=0.99

P=0.05

P=0.05


Mehran RM et al. Eur Heart J 2009 June ; 30: 1457-1466

Influence of Major Bleeding and MI within 30 Days on Risk of Death Over 1 Year



Of 13,819 enrolled pts, 524 (3.8%) died within 1 year

Myocardial infarction 3.1 (2.4-3.9) <0.001

Major bleeding 3.5 (2.7-4.4) <0.001

Blood transfusion 4.5 (3.4-5.9) <0.001

HR ± 95% CI P-valueHR (95% CI)

Death

Log Rank P=0,00013

Nodiscontinuation vs early discontinuation: p < 0.001Nodiscontinuation vs late discontinuation: p = 0.223Early discontinuation vs late discontinuation: p = 0.011Nodiscontinuation vs early+late discontinuation: p = 0.018

No discontinuation

Early Discontinuation

Late discontinuation

Stent Thrombosis

No discontinuation


Late discontinuation Nodiscontinuation vs early discontinuation: p = 0.015Nodiscontinuation vs late discontinuation: p = 0.175Early discontinuation vs late discontinuation: p = 0.653Nodiscontinuation vs early+late discontinuation: p = 0.009

MACE

Nodiscontinuation vs early discontinuation: p < 0.001Nodiscontinuation vs late discontinuation: p = 0.117Early discontinuation vs late discontinuation: p = 0.313Nodiscontinuation vs early+late discontinuation: p < 0.001

No discontinuation



25

44,9

10,913

0102030405060708090

100

MACE Antiplateletdiscontinuation

Minor Bleeding and Long-Term Outcome

%

Minor bleeding

No bleeding

P<0.001P=0.001


Table 2. Cumulative, 30-day and 12-month rates of any bleeding .

Bleeding at follow upBleeding at 30 days Bleeding at 12 months

No(N=1,286)

Yes(N=151)

P

No

(N=1,371)

Yes(N=166)

P

No

(N=1,314)

Yes(N=123)

Cumulative MACE 12.4 31.1 < 0.001

13.6 30.3 < 0.001

12.7 31.7

Any death 4.6 11.3 0.001 5.0 10.6 0.08 4.7 11.4

MI 4.2 8.6 0.015 4.6 6.1 0.545 4.3 8.1

UA leading to hospitalization 3.8 11.3 < 0.001

4.3 10.6 0.028 3.9 12.3

Non fatal stroke 0.5 1.3 0.240 0.5 3.0 0.061 0.5 1.6

Cumulative cardiac death 1.0 5.3 0.001 1.3 4.5 0.068 1.1 5.7

Any stent thrombosis 3.2 6.6 0.031 3.4 7.6 0.08 3.1 8.1

Log rank = 0.003

A) MACE free survival

No major bleeding at 30 daysMajor bleeding at 30 days

Log rank = 0.051

A) Any ST free survival


Log rank < 0.001

A) MACE free survival

No major bleeding at 12 monthsMajor bleeding at 12 months

Log rank < 0.001

A) Any ST free survival


CV

de

ath

, M

I or

str

oke

Days

CLOPIDOGREL PPI vs no PPI: Adj HR 0.94, 95% CI 0.80-1.11

PPI use at randomization (n= 4529)

Clopidogrel

Prasugrel

PRASUGREL PPI vs no PPI: Adj HR 1.00, 95% CI 0.84-1.20

Primary endpoint stratified by use of a PPI

O’Donoghue ML, Braunwald E, Antman EM, et al. Lancet. 2009.

Efficacy of Antiplatelet Therapy in Reducing Coronary Events after Stenting

Efficacy of Antiplatelet Therapy in Reducing Coronary Events after Stenting

0,81,6

0,5

5,6 5,7

3,9

6,2

3,6

11

8,3

2,7

0

3

6

9

12

Hall (1996) ISAR (1997) STARS (1998) MATTIS(1998)

FANTASTIC(1998)

ASA+Ticlopidine ASA only ASA + Warfarine

N=226 N=517 N=1653 N=350 N=485

P=0.1

P=0.01

P<0.001

P=0.07P=0.37

Cum

ulat

ive

Eve

nt R

ate

%





Joner et al., JACC 2006 48:193-202Joner et al., JACC 2006 48:193-202

68 DES > 30 days68 DES > 30 days

0

20

40

60

80

100

1 2 3 4 5 6 7 8 9 111516 2017Months

%

E

ndo

the

lializ

atio

n

DES

BMS

>400

20

40

60

80

100

1 2 3 4 5 6 7 8 9 111516 2017Months

%

E

ndo

the

lializ

atio

n

DES

BMS

>40

DESDES

BMSBMS

Possible Mechanisms Linking Post-Percutaneous Coronary

Intervention Bleeding With Increased Mortality

Doyle B Am Coll Cardiol 2009;53:2019–27

Risk of All-Cause Mortality and Recurrent ACS in Patients Taking Clopidogrel and PPI

Ho PM, Maddox TM, Wang L, et al. JAMA. 2009;301(9):937-944

0.70

0.60

0.50

0.40

0.30

0.20

0.10

00 90 180 270 360 450 540 630 720 810 900 990 1080

Days Since Discharge

Pro

po

rtio

n o

f D

eath

s o

r R

ecu

rre

nt A

CS

Neither clopidogrel nor PPIPPI without clopidogrelClopidogrel + PPIClopidogrel without PPI

Log rank = 0.019

30-day Bleeding and Long-Term Mortality



Log rank < 0.001


12-month Bleeding and Mortality


ConclusionConclusionS

urvi

valf

ree

from

Ste

ntT

hrom

bosi

s(%

)

100100

9090

8080

7070

6060

5050

40404848

3636

2424

1212

00

Log rank testOverall: p=0.031No discontinuation vs early discontinuation: p=0.015No discontinuation vs late discontinuation: p=0.175Early discontinuation vs late discontinuation: p=0.653No discontinuation vs early+late discontinuation: p=0.009

Months



No discontinuation

Overall death and discontinuationOverall death and discontinuation

100100

9090

8080

7070

6060

5050

4040

48483636

24241212

Sur

viva

l(%

)

Months




No discontinuation



Clopidogrel was to be maintained for 12 months

Pts were followed-up for 32.4±11.3 months

86,4%

8,8% 4,8%

No discontinuation



Discontinuation Causes:

� Surgery 34.5% � Bleeding 21%� Medical decision 17.6%� Dental interventions 7.6%� Economic/burocratic reasons 5.9% � Anticoagulant therapy 5.0%

Premature Discontinuation of Antiplatelet Therapy after Drug Eluting Stent Implantation


ConclusionConclusion

100100

9090

8080

7070

6060

5050

4040

4848363624241212

Sur

viva

lfre

efr

om

MA

CE

(%

)




No discontinuation

Association between thienopyridine and/or aspirin discontinuation and MACE stratified by time intervals

Discontinuation of Thienopyridine after DESDiscontinuation of Thienopyridine after DES

Mor

talit

y

%

Discontinued

Continued

1 2 3 4 5 6 7 8 9 10 11 120

5

10

15

p<0.001

Months

7.5 %

0.7 %

Spertus et al, Circulation 2006;113:2803-2809

PREMIER Registry: 500 DES treated MI pts

Possible Mechanisms Linking Post-Percutaneous Coronary

Intervention Bleeding With Increased Mortality

Doyle B Am Coll Cardiol 2009;53:2019–27

Bleeding and dual antiplatelet therapy

1,23,4

0123456789

10

major bleeding minor bleeding

30-day Bleeding

%

12-month Bleeding

3

6,9

0123456789

10

major bleeding minor bleeding

%



25

44,9

10,913

0102030405060708090

100

MACE Antiplateletdiscontinuation

Minor Bleeding and Long-Term Outcome

%

Minor bleeding

No bleeding

P<0.001P=0.001


Long-term triple therapy with aspirin, clopidogrel, and warfarin18-month TIMI Major and Minor Bleeding

Long-term triple therapy with aspirin, clopidogrel, and warfarin18-month TIMI Major and Minor Bleeding

%

Mean INR at the time of bleeding was 3.1±0.7

2,9

7,8

22,9

0

5

10

15

Major bleeding Minor bleeding

triple therapy (N=102) dual therapy (N=102)

P=0.6

P=0.1

R. Rossini et al. Am J Cardiol 2008 in press

All bleeding cumulative distribution

100

90

80

70

60

500 200 300 450 600

%

Double therapy

Triple therapy

P=0.13

95.1 %

89.2 %

Days

Ble

edin

g ev

ent f

ree

surv

ival


Long-term triple therapy with aspirin, clopidogrel, and warfarin

100

90

80

70

60

500 200 300 450 600

%

Double therapy

Triple therapy with INR < 2.6

All bleeding cumulative distribution by INR

95.1 %

95.1 %

Days

Ble

edin

g ev

ent f

ree

surv

ival

Triple therapy with INR ≥ 2.6

66.7 %

†

‡

† P<0.0001 vs Double therapy

‡ P<0.0001 vs Triple with INR <2.6R. Rossini et al. Am J Cardiol 2008 in press

Long-term triple therapy with aspirin, clopidogrel, and warfarin

5,84,9

0

5

10

15

20triple therapy dual therapy

%

P=0.7


Long-term triple therapy with aspirin, clopidogrel, and warfarin18-month MACE

Long-term triple therapy with aspirin, clopidogrel, and warfarin18-month MACE

Aspirin Hypersensitivity Related Symptoms(N=52)

Aspirin Hypersensitivity Related Symptoms(N=52)

3929

302

Urticaria Angioedema Asthma Anaphylactic shock

%

%

%

%


Days

Sur

viva

l Pro

babi

lity

0 30 60 90 120 150 180 210 240 270 300 330 360 390

0.90

0.92

0.94

0.96

0.98

1.00

Placebo

Treated

Survival Curves for PPI Treated vs PlaceboComposite Cardiovascular Events

Adjustment through Cox Proportional Hazards ModelAdjustment through Cox Proportional Hazards ModelAdjusted to Positive NSAID Use and Positive H. Pylori StatusAdjusted to Positive NSAID Use and Positive H. Pylori Status

HR = 1.0295% CI = 0.70; 1.51

COGENT Trial ResultsTCT ‘09

HR = 0.5595% CI = 0.36; 0.85

p=0.007

Reduction of GI events by PPI

%

53,1

1,2

7,8

2,1 2,14,2

0,8 1,7

8,1

3,1 3,1

0

5

10

15

20

25

MACE Death Stent Thrombosis

No PPI (n=170) Lansoprazolo (n=855)

Omeprazolo (n=125) Pantoprazolo (n=178)


P=0.46

P=0.62P=0.67


Clopidogrel is a prodrug. It requires the conversio n by the liveClopidogrel is a prodrug. It requires the conversio n by the live r primarily via r primarily via CYP3A4 and CYP2C19 to an active metaboliteCYP3A4 and CYP2C19 to an active metabolite

PPIs are strong inhibitors of CYP2C19 activityPPIs are strong inhibitors of CYP2C19 activity

Clopidogrel and PPIs Clopidogrel and PPIs –– The OCLA studyThe OCLA study

PRI: Platelet Reactivity Index as measured by vasodilator stimulated phosphoprotein (VASP)

Gilard et al. J Am Coll Cardiol 2008;51:256-60.

p<0.0001

Studio CURE: Primary Endpoint MI / Stroke / CV Death

Months of Follow-Up

Yusuf S et al. N Engl J Med. 2001;345:494-502.

0.00

0.02

0.04

0.06

0.08

0.10

0.12

0.14

Cum

ulat

ive

Haz

ard

Rat

e

Clopidogrel + ASA*

3 6 9

Placebo + ASA*

P=0.00009N=12,56220% RRR

0 12*Other standard therapies were used as appropriate.

Duplice antiaggregazione nelle sindromi coronariche acute

NSTEACS

ACCP Guidelines 2008

Aderenza alla terapia

"il coinvolgimento attivo, volontario e collaborativo del paziente,

finalizzato a produrre un risultato terapeutico"

tra i pazienti dimessi dopo un infarto miocardico acuto in terapia

con aspirina, statine e beta-bloccanti, circa il 34% dei pazienti sospende almeno 1 dei 3 farmaci

ed il 12% li sospende tutti e 3 entro il primo mese dalla

dimissione

terapia tra 6 e 12 mesi dopo la diagnosi angiografica di

cardiopatia ischemica Il 71% dei pazienti prosegue la terapia con

aspirina, mentre meno della metàmantiene la terapia con beta-

bloccanti (46%), ipolipemizzanti(44%), e solo il 21% continua la

terapia con tutti e 3 i farmaci.

Newby LK, et al. Circulation. 2006;113:203-212

Newby LK, et al. Circulation. 2006;113:203-212

Switching from intensive to moderate statin therapy after an acute coronary event

Switching from intensive to moderate statin therapy Switching from intensive to moderate statin therapy

after an acute coronary eventafter an acute coronary event

1,321 patients discharged on atorvastatin 80mg/day*

557 (42%) switched to moderate statin therapy

Median time to switching 28 days (IQR 16–67 days)

102 (18%) switched to a lower dose of atorvastatin

Mean dose 24mg/day

327 (59%) switched to simvastatin

Mean dose 27mg/day

57 (16%) switched to pravastatin

Mean dose 40mg/day

41 (7%) switched to fluvastatin

Mean dose 80mg/day

486 (37%) continued atorvastatin

80mg/day

278 (21%) discontinued therapy

Median time to discontinuation 37 days (IQR 19–81 days)

*1321 consecutive patients (886 men, mean age 71.1 ± 8.7 years) discharged on atorvastatin 80mg/day after an ACS in a 6.5-year period

Colivicchi F, et al. Int J Cardiol (2010), doi:10.1016/j.ijcard.2010.07.006

SICI-GISE Consensus DocumentSICI-GISE Consensus Document

�The Italian Society of InterventionalCardiology (GISE) recommends a 12-month dual antiplatelet therapy after DES placement

Journal Cardiovascular Medicine 2007; 10:782-791Journal Cardiovascular Medicine 2007; 10:782-791

Research Only

Not Commercially Available

Research Only

Not Commercially Available

Late Stent Thrombosis

Colivicchi F, et al. Int J Cardiol (2010), doi:10.1016/j.ijcard.2010.07.006

Association between switching and MACEsAssociation between switching and MACEs

Riddell, J. W. et al. Circulation 2007;116:e378-e382

Coronary Stent Thrombosis and Non-cardiac Surgery

Nuovo Protocollo di studioStenting coronarico e chirurgia:

Rischio di trombosi dello stent e rischio emorragico

Rilevare il numero di pazienti con pregresse procedure interventistiche coronariche + stenting sottoposti a interventochirurgico (cardiochirurgia, chirurgia generale, ortopedica, traumatologica, urologica, ginecologica, neurochirurgica, oculistica, dermatologica, odontoiatrica, otorino-laringoiatrica) presso gli OO.RR.Bg nell’arco di 6 anni (2003-2009)

Determinare il rischio di trombosi dello stent e di eventi emorragici nella fase peri- e post-operatoria (30 giorni) in rapporto al tipo di stent e di terapia antiaggregante in corso, ed al tempo intercorso tra impianto di stent e chirurgia



Discuntinuation of Both

Discuntinuation of Thienopyridines Only

Discuntinuation of Aspirin Only

No Discontinuation

P=1.0

P=0.88

P = 0.20

P=0.26

P=0.001

P = 0.24P=0.08

P=0.002

P=0.001

P=1.00

P=0.11

P = 0.07

%

Log rank p = 0.019

30-day Bleeding and Long-Term Mortality



Log rank p < 0.001

12-month Bleeding and Long-Term Mortality

Time of major bleeding and long-term outcome


Aderenza terapeutica: il fattore di rischio occulto · • 2002 anterior MI primary PCI (BMS) on...

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