Inappropriate clopidogrel adherence explains stent related adverse outcomes

1. Inappropriate clopidogrel adherence explains stent related adverse outcomes Leonardo Tamariz, MD, MPH University of Miami

2. 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.

3. 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.

4. Specific aims • To evaluate clopidogrel medication adherence in a cohort of patients with stents. • To evaluate if clopidogrel adherence affects stent related outcomes.

5. Methods: Data source Humana EDW Medical File ICD 9 codes Member File Demographics Costs Provider information Pharmacy File GPI codes Dosage Refill patterns

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

7. ∑ days supply of medication MPR = ∑ number of days between first and last refill + days supply of last refill 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.

8. 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

9. 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).

10. 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.

11. Results: Baseline characteristics

12. Results: Distribution of MPRs

13. Results: Predictors of inappropriate clopidogrel use

14. Results: Incidence of MI by adherence to clopidogrel HR 1.35(1.08-1.70)p=0.009

15. Results: Incidence of death by adherence to clopidogrel HR 1.32(1.12-1.55)p<0.01

16. Results: Incidence of combined outcome by adherence to clopidogrel HR 1.31(1.11-1.54)p<0.01

17. 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.

18. 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.

19. 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.