Prevalence, Predictors, and Long-Term Prognosis of Premature Discontinuation of Oral Antiplatelet Therapy After Drug Eluting Stent Implantation

Roberta Rossini, MD, PhD, Davide Capodanno, MD, Corrado Lettieri, MD, Giuseppe Musumeci, MD, Tamar Nijaradze, MD, Michele Romano, MD, Nikoloz Lortkipanidze, MD, Nicola Cicorella, MD, Giuseppe Biondi Zoccai, MD, Vasile Sirbu, MD,

Antonio Izzo, MD, Giulio Guagliumi, MD, Orazio Valsecchi, MD, Antonello Gavazzi, MD and Dominick J. Angiolillo, MD, PhD

USC Cardiologia, Dipartimento Cardiovascolare, Ospedali Riuniti di Bergamo, Italy

Divisione di Cardiologia, Ospedale Carlo Poma, Mantova, Italy

Divisione di Cardiologia, Università di Torino, Italy

University of Florida College of Medicine- Jacksonville, Florida, US

American Journal of CardiologyVolume 107, Issue 2, Pages 186-194 (January 2011)

DOI: 10.1016/j.amjcard.2010.08.067

Copyright © 2011 Elsevier Inc. Terms and Conditions

Aim of the StudyAim of the Study

The aims of the present study were to determinethe prevalence and predictors of premature

discontinuation of long-term oral antiplatelet therapy after DES implantation and to evaluate its

effects on prognosis in relation to the time and duration of the discontinuation

MethodsMethods

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 maintained for 12 months

Pts were followed-up for 32.4±11.3 months

Prevalence and predictors of aspirin and/or clopidogrel discontinuation were assessed

Major adverse cardiac events (MACE), defined as death, acute coronary syndrome leading to hospitalization, and stroke, were recorded. Probable/possible/definite stent thrombosis were also recorded

86,4%

8,8% 4,8%

No discontinuation

Early discontinuation

Late discontinuation Rossini R et al. Am J Card 2011, 107: 186-194

Discontinuation Causes:

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

ResultsResults

8.8% of patients discontinued one or both antiplatelet agents within the first 12 months (early discontinuation) and 4.8% withdrew aspirin after 1 year (late discontinuation)

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)

Rossini R et al. Am J Card 2011, 107: 186-194

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, 107: 186-194

Overall death and discontinuation

100

90

80

70

60

50

40

48362412

Sur

viva

l (%

)

Months

Log rank testOverall: p=0.001No discontinuation vs early discontinuation: p=0.001No discontinuation vs late discontinuation: p=0.223Early discontinuation vs late discontinuation: p=0.011No discontinuation vs early+late discontinuation: p=0.018

Late discontinuation

Early discontinuation

No discontinuation

Rossini R et al. Am J Card 2011, 107: 186-194

100100

9090

8080

7070

6060

5050

4040

4848363624241212

Sur

viva

l fre

e fr

om M

AC

E (

%)

Log rank testOverall: p=0.001No discontinuation vs early discontinuation: p=0.001No discontinuation vs late discontinuation: p=0.223Early discontinuation vs late discontinuation: p=0.011No discontinuation vs early+late discontinuation: p=0.018

Late discontinuation

Early discontinuation

No discontinuation

MACE and discontinuation

MonthsRossini R et al. Am J Card 2011, 107: 186-194

Surv

ival

fre

e fr

om S

tent

Thr

ombo

sis

(%) 100100

9090

8080

7070

6060

5050

4040484836362424121200

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

Late discontinuation

Early discontinuation

No discontinuation

Stent Thrombosis and discontinuation

Rossini R et al. Am J Card 2011, 107: 186-194

Death, 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

Rossini R et al. Am J Card 2011, 107: 186-194

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

Discuntinuation of BothDiscuntinuation 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

%

Rossini R et al. Am J Card 2011, 107: 186-194

ConclusionsConclusions

• Premature discontinuation of antiplatelet therapy is relatively common, especially within the first year, and strongly associated with increased cardiovascular events, including ST and death.

• Early discontinuation of antiplatelet agents within the first year was predicted by in-hospital major bleeding, oral anticoagulant use at discharge, and the lack of statin prescription.

• Strategies to improve compliance to antiplatelet therapy in patients with greater likelihood to interrupt treatment are warranted