Inappropriate clopidogrel adherence explains stent related adverse outcomes Leonardo Tamariz, MD,...
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Transcript of Inappropriate clopidogrel adherence explains stent related adverse outcomes Leonardo Tamariz, MD,...
Inappropriate clopidogrel adherence explains stent related adverse outcomes
Leonardo Tamariz, MD, MPHUniversity of Miami
Antiplatelet use post-stent
• Angioscopic studies show lack of neo-intimal coverage and thrombi post-stent.
• Drug eluting stents have been associated to late MI.
• ACC/AHA/SCAI recommends in patients with low bleeding risk maintaining clopidogrel for 12 months after a stent.
• Clopidogrel is now a chronic medication.
Consequences of lack of medication adherence in CV
disease• Inadequate disease control.• Low adherence to beta-blockers or statins
in post MI patients increases the death rate.
• Represents a significant burden to healthcare utilization – the estimated yearly cost is $396 to $792 million.
• One – two thirds of all medication-related hospital admissions are attributed to nonadherence.
Specific aims
• To evaluate clopidogrel medication adherence in a cohort of patients with stents.
• To evaluate if clopidogrel adherence affects stent related outcomes.
Methods: Data source
Humana EDW
Medical FileICD 9 codesMember File
DemographicsCostsProvider information
Pharmacy FileGPI codes DosageRefill patterns
Methods: Study design
3.2 ± 0.7 years
Clopidogrel adherenceClopidogrel adherence
Inclusion criteria•18 years or older• Procedure claim for bare metal stent (36.06) or drug eluting stent (36.07) between January 1, 2003-June 1, 2005.
Stents(n=7,091)
Clopidogrel users(n=5,838)
Non- clopidogrel users(n=1,253)
MIDeath
Methods: Clopidogrel adherence
• Clopidogrel use defined by Generic Product Identifiers (GPI code:85158020)
• Adherence defined by medication possesion ratios (MPR).– Appropriate adherence: 80% or more MPR– Innapropriate adherence: <80% MPR.
∑ days supply of medication
∑ number of days between first and last refill + days supply of last refill
MPR =
Methods: Outcomes
• Myocardial infarction– ICD 9 code 410.x with a hospitalization
• Death (all cause mortality)– Social security death index match
• Combined– MI or death
Methods: CV risk factors (ICD-9 definitions)
• Diabetes (250.xx)• Hypertension (401.xx, 402.xx,
403.xx,404.xx,405.xx)• Abnormal lipid panel (272.xx),• Obesity (278, 278.0, 278.00, 278.01,
278.1).
Methods: Statistical analysis
• Baseline characteristics with chi-square and t-test• Predictors of innapropriate use with logistic
regression• Person-time and hazard ratios of events using
Cox proportional adjusted for demographics, claims for CV risk factors, claims for heart failure, type of stent and MI at presentation.
Results: Baseline characteristics
CharacteristicCharacteristic Entire Entire cohortcohort(n=5,838)(n=5,838)
Clopidogrel Clopidogrel users with users with
appropriate appropriate adherence adherence (n=4,548)(n=4,548)
Clopidogrel users Clopidogrel users with with
inappropriate inappropriate adherenceadherence(n=1,290)(n=1,290)
p-valuep-value
Age, years 63.311.6 63.511.5 62.711.9 0.04
Female gender, % 33 24 21 <0.01
Previous history of myocardial infarction, %
18 18 18 0.92
Previous history of hypertension, %
55 54 57 0.18
Previous history of diabetes, %
28 27 32 <0.01
Previous history of abnormal lipids, %
48 48 48 0.95
Previous history of heart failure, %
10 9 11 0.01
Medicare, %
58 55 59 0.08
Drug eluting stents, %
84 84 85 0.49
Results: Distribution of MPRs0
1020
3040
Per
cent
0 .2 .4 .6 .8 1Medication possesion ratio
Results: Predictors of inappropriate clopidogrel use
Predictors OR (95% C.I)
Age 0.97 (0.97-0.98)
Female gender 0.79 (0.69-0.91)
Diabetes 1.2 (1.0-1.4)
Medicare insurance 1.5 (1.26-1.81)
0.02
0.04
0.06
0.08
0.10
Cu
mm
ulat
ive
inci
den
ce
0 1 2 3Years
Appropriate clopidogrel adherence
Innappropriate clopidogrel adherence
Results: Incidence of MI by adherence to clopidogrel
HR 1.35(1.08-1.70)p=0.009
0.00
0.10
0.20
0.30
0.40
Cu
mm
ulat
ive
inci
den
ce
0 1 2 3Years
Appropriate clopidogrel adherenceInnappropriate clopidogrel adherence
Results: Incidence of death by adherence to clopidogrel
HR 1.32(1.12-1.55)p<0.01
0.00
0.05
0.10
0.15
Cu
mm
ulat
ive
inci
den
ce
0 1 2 3Years
Appropriate clopidogrel adherenceInnappropriate clopidogrel adherence
Results: Incidence of combined outcome by adherence to
clopidogrel
HR 1.31(1.11-1.54)p<0.01
Conclusions
• Twenty eight percent of clopidogrel users post-stent deployment are not adherent.
• Lack of adherence to clopidogrel post-stent increases the risk of myocardial infarction and death.
Limitations
• Lack of validation of exposure and outcomes.
• Insured patient population, less burden of disease compared to other studies.
• Unable to document ASA use, coronary anatomy where stent was placed due to use of administrative claims.
Clinical implications and unresolved issues
• We need to stress the importance of clopidogrel adherence after a stent.
• We need to inquire patients about clopidogrel adherence post-stent.
• We need to identify individual reasons for lack of clopidogrel adherence.
• Need a randomized trial to determine the efficacy of different interventions to improve clopidogrel adherence.