Inappropriate clopidogrel adherence explains stent related adverse outcomes Leonardo Tamariz, MD, MPH University 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 File ICD 9 codes Member File Demographics Costs Provider information Pharmacy File GPI codes Dosage Refill patterns

Methods: Study design 3.2 ± 0.7 years Clopidogrel 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, Stents (n=7,091) Clopidogrel users (n=5,838) Non- clopidogrel users (n=1,253) MI Death

Methods: Clopidogrel adherence Clopidogrel use defined by Generic Product Identifiers (GPI code: ) 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, , , 278.1).

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 Characteristic Entire cohort (n=5,838) Clopidogrel users with appropriate adherence (n=4,548) (n=4,548) Clopidogrel users with inappropriate adherence (n=1,290)p-value Age, years 63.3   Female gender, %332421<0.01 Previous history of myocardial infarction, % Previous history of hypertension, % Previous history of diabetes, % <0.01 Previous history of abnormal lipids, % Previous history of heart failure, % Medicare, % Drug eluting stents, %

Results: Distribution of MPRs

Results: Predictors of inappropriate clopidogrel use PredictorsOR (95% C.I) Age0.97 ( ) Female gender0.79 ( ) Diabetes1.2 ( ) Medicare insurance1.5 ( )

Results: Incidence of MI by adherence to clopidogrel HR 1.35( )p=0.009

Results: Incidence of death by adherence to clopidogrel HR 1.32( )p<0.01

Results: Incidence of combined outcome by adherence to clopidogrel HR 1.31( )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.