Assessing the Impact of Medication Adherence on Long-term Outcomes Post

Myocardial Infarction

S. Bansilal, JM. Castellano, HG. Wei, E. Garrido, A. Freeman, CM. Spettell, F. Garcia-Alonso, G.

Steinberg , G. Sanz, V. Fuster

European Society Of Cardiology Congress 2014

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Disclosures

• Drs. Bansilal, Castellano, Sanz and Fuster have no relevant disclosures.

• Ms. Garrido and Dr. Garcia-Alonso are employees of Grupo Ferrer.

• Drs. Wei, Steinberg, Spettell and Ms. Freeman are employees of Aetna.

Background

• Evidence based medications for secondary prevention of cardiovascular disease (CVD) have led to a 50% reduction in mortality

• Nearly half of the patients are non adherent within the first year post event.

• Long-term studies linking adherence with outcomes are limited.

• We attempted to study the association between levels of medication adherence and long-term major adverse cardiovascular events in patients post myocardial infarction (MI).

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Study Aims

• Evaluate the association of levels of medication adherence with long-term major cardiovascular events- death, hospitalization for MI, stroke and coronary revascularization.

• Evaluate the association of levels of medication adherence with ‘softer’ cardiac outcomes –hospitalization for angina, All-cause and cardiac –related visited to ED.

• Evaluate the association of levels of medication adherence with resource utilization- outpatient visits to a cardiac specialist and cardiac testing.

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Methods

Data Collection

• 2010-2013 data from Aetna Commercial & Medicare

Advantage population databases

• Enrolment records, medical and pharmacy health insurance

claims.

• Records linked for comprehensive tracking of individuals’ use

of healthcare resources and clinical outcomes over time and

across providers.

• Symmetry Episode Risk Groups (ERG®) Scores & publicly

available data from the U.S. Census 2010 file used

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MethodsInclusion Criteria:• Adults who initiated both statin and ace-inhibitor (ACEI) medications

following a hospitalization discharge for myocardial infarction (MI) based on ICD codes with a length of stay of more than 2 days, between January 1, 2010, and February 28, 2013.

• Continuous eligibility for both medical and prescription drug benefits from Aetna during 6 months before and after the MI.

Exclusion Criteria:• Pregnant • Diagnosis codes indicating psychoses, dementia, bipolar disorder, major

depressive disorder (severe with psychotic behaviours) or alcohol/substance abuse

• Living in a nursing home or in a hospice or respite care.• Patients who had a refill for ARB medication within 6 months following the

discharge date of the MI

Methods• Most recurrent events post MI occur within the first

year• Patients ‘reveal’ their adherence patterns as early as

a month post MI, but their stable pattern is best apparent around 6 months and beyond

• Studies evaluating adherence have typically selected a 6-12 month exposure period

• We chose a 6 month adherence assessment period to optimize rigor while maintaining power

1. Smolina K etal. Circ Cardiovascular Qual. Outcomes 20122. Ho PM etal.- Arch. Int Med 2006 ; Am Heart J 2008; Circulation 2009 3. Jackevicius CA etal. Circulation 20084. Choudhry NK etal. Am Heart J 2014

Methods

Adherence assessment

• Proportion of days covered (PDC) for both statin and ACEI during 6 months of follow-up after the index prescription.

• Patients were considered to be adherent if they were getting the refill of both ACEI and statin prescriptions.

• Based on their PDCs, we categorized patients into one of three groups using standard thresholds: ≥80% (‘fully adherent’), 40–79% (‘partially-adherent’), and <40% (‘non-adherent’).

Statistical Analyses

• Descriptive analyses were conducted to compare baseline characteristics between adherence exposure groups.

• Time to MACE for the three exposure groups was compared using Cox Proportional Hazards regression.

• Adjustment for significant confounders including those related to the “healthy adherer effect”.

• Event counts were compared using Negative Binomial regression with adjustment for confounders as above.

Covariates included for adjustment

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Consort Diagram

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n=1263

Adults post- MI 1/10/10-2/28/13

N=14,119 7012 (49.6%) No fill of both ACEI and Statin

during 6 months post MIAdults post MI with ACEI and Statin fill within 6

month post eventN=7107

Adults post MI with ACEI and Statin fill within 6 month post event, No

exclusionN=5776

1331 excluded • 29% mental

disorders• 1%

pregnant/delivery

• 10% Hospice• 23% Nursing

facility• 33% ARB fill

during 6 months post MI

• 4% MI was not index event

1761 without 6 months pre-periodAdults post MI with ACEI and

Statin fill within 6 month post event, No exclusion, with 6

mth pre-periodN=4015

Fully-Adherent (>80%) N=1721 (43%)

Partially-Adherent (40-79%) N=1031 (31%)

Non-Adherent (<40%) N=1263 (26%)

Baseline Characteristics

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Low PDC

Mid PDC High PDC p value

Age (mean) 56.6 57.8 56.2 0.0002 Male gender (%) 74.01 76.72 79.31 0.005 PDC (mean) 21 62 93 <0.0001 Diabetes (%) 34.05 34.20 25.63 <0.0001

Hyperlipidemia (%) 91.76 94.62 95.41 0.0003

Hypertension (%) 68.19 77.12 68.97 <0.0001 Previous CAD (%) 31.30 34.52 21.50 <0.0001 Previous CVD (%) 5.92 7.21 5.69 0.215

Previous PAD (%) 7.57 8.79 5.75 0.006

Obesity (%) 4.46 5.78 4.65 0.259 CHF (%) 20.66 20.43 17.26 0.033 CRF (%) 4.17 5.86 3.78 0.021

Prospective risk score (ERG) (mean) 2.96 3.29 2.50 <0.0001

Charlson Comorbidity Score (mean) 1.91 2.04 1.82 <0.0001

Length of Stay - Index Admission (mean) 4.2522 4.5701 4.0622 0.0084 Household income in zip code (median) 64336 66058 66827 0.031 Copays for all medications during adherence period (mean)

488 570 592 <0.0001

Time to Major cardiac Event by Adherence Levels

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Primary Outcome Measures

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Fully adherent (High PDC) group showed statistically significant lower events across the board when compared with partially adherent and non-adherent groups. Outcomes were not statistically different

for the partially adherent and non-adherent groups.

Event Low PDC (N=1031)

Mid PDC (N=1263)

High PDC (N=1721)

PDC group comparison Ratiop value

Composite Cardiac Events 18.1 (281) 17.2 (329) 12.8 (328) High v. Low 0.72 0.002High v. Mid 0.81 0.01 Mid v. Low 0.90 0.18

Coronary/MI Hospitalization 4.8 (74) 4.4 (84) 2.3 (58) High v. Low 0.54 0.001High v. Mid 0.59 0.01 Mid v. Low 0.90 0.57

Stroke Hospitalization 1.2 (18) 0.9 (17) 0.6 (16) High v. Low 0.54 0.09High v. Mid 0.94 0.86 Mid v. Low 0.58 0.14

Revascularization Procedures (IP or OP)

14.4 (224) 13.1 (249) 10.8 (277) High v. Low 0.78 0.01

High v. Mid 0.86 0.12 Mid v. Low 0.90 0.30

Secondary Outcome Measures

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Other than All cause ER visits, none of the other outcomes were statistically significant

Event Low PDC (N=1031)

Mid PDC (N=1263)

High PDC (N=1721)

PDC group comparison Ratio p value

Hospitalization related to angina and CV atherosclerosis

7.6 (118) 8.1 (154) 5.8 (149) High v. Low 0.82 0.14

High v. Mid 0.79 0.06 Mid v. Low 1.04 0.78

All-Cause ER Visits 39.4 (406)37.3 (471) 31.3 (539) High v. Low 0.71 <0.001High v. Mid 0.89 0.08 Mid v. Low 0.80 0.002

Cardiac-Related ER visits 3.0 (47) 2.6 (50) 2.7 (70) High v. Low 0.89 0.64High v. Mid 1.07 0.78 Mid v. Low 0.83 0.49

Secondary Outcome Measures

Event Low PDC (N=1031)

Mid PDC (N=1263)

High PDC (N=1721)

PDC group comparison Ratio p value

OP Cardiologist visits with CV testing

49.9 (777) 49.4 (944) 51.5 (1320) High v. Low 1.00 1.00

High v. Mid 1.01 0.80 Mid v. Low 0.99 0.83

General OP Cardiologist office visits

297 (4622) 305.4 (5832) 299.7 (7687) High v. Low 1.02 0.63

High v. Mid 1.01 0.71 Mid v. Low 1.00 0.90

Discussion

• The Challenge of poor adherence

• Ho etal. –VA database

• MI-FREEE-Randomized trial

• Novel strategies to enhance adherence

• Polypill

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Limitations

• Insurance and pharmacy claims database

• Lack of benefit for secondary outcomes

• Overlap of outcomes with the adherence assessment period

• Unable to directly establish causality

• Confounding bias

• Treatment initiation

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Conclusions

• High levels of adherence to guideline recommended therapies are associated with a lower rate of major cardiovascular events compared to partial or non-adherence.

• There appeared to be a threshold effect for this benefit at >80% adherence.

• Novel approaches to improve adherence such as a polypill that may enable >80% adherence with secondary preventive therapies may lead to a significant reduction in CV events post MI.

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Clinical Trial Update Hotline: Infarction, interventions and outcomes

September 2nd, 2014 Barcelona-Central Village

17:42- FOCUS - Fixed dose combination drug for secondary prevention

Valentin Fuster, M.D, PhD

Thank you Aetna patients!