Collaborating for Impact
National Forum for Heart Disease and Stroke Prevention
12th Annual Meeting October 22, 2014
Helene D. Clayton-Jeter, O.D.
Director, Cardiovascular and Endocrine Liaison Program
Commissioner’s Office of External Affairs
Food and Drug Administration
Fortunato Fred Senatore MD, PhD, FACC
Medical Officer
Division of Cardiovascular and Renal Products
Food and Drug Administration
1
Presenter Disclosure
The opinions and content in this
presentation are based on personal
views and do not reflect positions
or policies of the FDA.
2
Million
®
Hearts
Goal: Prevent 1 million heart attacks
and strokes by 2017
• National initiative co-led by CDC and CMS
• In partnership with federal, state, and private organizations
innovating and implementing
• To address the causes of 1.5M events and 800K deaths a
year, $312.6 B in annual health care costs and lost
productivity and major disparities in outcomes
From presentation by Janet Wright, MD, FACC, Executive Director, MH Initiative
3
Key Components of Million
Hearts®
Excelling in the ABCS
Optimizing care
Health Keeping Us Healthy
Disparities Changing the context
Prioritizing
the ABCS
Health tools
and technology
Innovations in
care delivery
TRANS
FAT
From presentation by Janet Wright, MD, FACC, Executive Director, MH Initiative
Million Hearts
• Three things must happen to prevent 1
million heart attacks and stroke
– 6.3 million smokers quit
– 10 million more people control their
hypertension
– 20% reduction in sodium intake
Focus on populations with greatest burden and at greatest risk
From presentation by Janet Wright, MD, FACC, Executive Director, MH Initiative
5
Preventing a Million:
Targets for Our Environment
2009-2010
Pre-Initiative
Estimate
2017 Target
26%
10% reduction
Sodium reduction
3580 mg/day
20% reduction
Trans fat reduction
0.6% of calories
100% reduction
Intervention
Smoking prevalence
From presentation
by Use
Janet
Wright,
MD, FACC, Executive Director, MH Initiative
National Survey on Drug
and Health
2009-2010
National Health and Nutrition Examination Survey 2009-2010
Preventing a Million: Targets for
the ABCS
Intervention
2009-2010
Pre-Initiative
Estimate
2017
Populationwide Target
2017
Clinical
Target
Aspirin when appropriate
54%
65%
70%
Blood pressure control
52%
65%
70%
Cholesterol management
33%
65%
70%
Smoking cessation
22%
65%
70%
National Ambulatory Medical Care Survey, National Health and Nutrition Examination Survey
Government/
Academia
FDA
Medication
Adherence
Strategies
Partnering
For Public
Health
Scientific
Research
Improved
Healthcare and
Care Delivery
Patients/Societies/Payers
8
Collaborating for Impact
Assess, Address, and Reduce Health Disparities
9
FDA Action Items to support
Million Hearts
Translate and
Disseminate Knowledge
Implement and Innovate
for Population Health
Research*
Liaison program,
newsletters, and webinars
targeting CV health
practitioners, patients,
patient advocates, and
consumers
Nutritional Fact Label
Campaign
•Label Youth Outreach
•Menu and Vending
Enhanced adherence
strategies for CV meds
Link MH website with
FDA’s CV webpage.
Conduct “the real cost”
tobacco cessation program
Evidence synthesis
focused on improved
patient outcomes
Publication:
•sodium levels for food
•partially hydrogenated oils
are not generally
recognized as safe
* Response to the
challenge to “push the
envelope”
10
Adherence: Multifaceted
faceted issue
Convenience
Pill
Burden/Day
Cost of
drugs
TI
Adherence
Rescue
Therapy
Patient
Attitude and
awareness
Test for
Adherence
PCP-Patient
Relationship
Symptom
of Disease
Health
Equity
TI = Therapeutic Index
11
Research Action Item-MH
Outcome Metrics Alliance
Rescue
Therapies
Professional
Academies
and Colleges
Evidencesynthesis on
improved
patient
outcomes
Strategy for
enhanced
adherence
TI
Pill
burden
Increased
public / sector
awareness
Improved
Care Delivery
ACL and
Administration
on Aging
TI = Therapeutic Index; ACL= Administration of Community Living
12
Why is adherence important?
• Assessing the Impact of Medication Adherence
on Long-term Outcomes Post Myocardial
Infarction
– Bansilal S, Castellano JM, Wei HG, Garrido E, Freeman E,
Spettell CM, Garcia-Alonso F, Steinberg G, Sanz G, Fuster V;
ESC Congress 2014
• Outcome: Time to MACE (death, hospitalization
for MI, stroke, coronary revascularization) by
Adherence Levels (Portion of Days Covered for
both statin and ACE-I as determined by
prescription pattern x 6 months
13
Time to MACE by Adherence Levels
14
Collaborating for Impact
• Conclusion
– Million Hearts promotes collaboration in CV
risk modification involving ABCS
– Million Hearts involves a multitude of
government agencies each tasked with
specific action items
– Mechanisms to enhance medication
adherence being examined
15
For additional information, contact the Commissioner’s Office of External Affairs,
Office of Health and Constituent Affairs, Million Hearts Liaison
Helene Clayton-Jeter, O.D. at cardio.endocrine@fda.hhs.gov or 301.796.8452
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Collaborating for Impact
Back-up
17
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
Bansilal et al, ESC 2014
18
Adherence Study-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).
Bansilal et al, ESC 2014
19
Adherence Study-Objectives
• 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.
Bansilal et al, ESC 2014
20
Adherence Study-Methods
• 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
Bansilal et al, ESC 2014
21
Adherence Study:
Inclusion/Exclusion
Inclusion 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
Bansilal et al, ESC 2014
22
Adherence Study: Endpoint Selection
• 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 et al. Circ Cardiovascular Qual. Outcomes 2012
2. Ho PM etal.- Arch. Int Med 2006 ; Am Heart J 2008; Circulation 2009
3. Jackevicius CA et al. Circulation 2008
4. Choudhry NK et al. Am Heart J 2014
Bansilal et al, ESC 2014
23
Adherence Study: 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’).
Bansilal et al, ESC 2014
24
Adherence Study: Statistical Analysis
• 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.
Bansilal et al, ESC 2014
25
Adherence Study:
Covariates for adjustment
Category
Sociodemographics
Copayment and
medication use
Use of medical
services
Comorbidities
Comorbidity
scores
Variables
Age, gender and race/ethnicity.
Health plan type (HMO vs. PPO), commercial or Medicare.
Estimated household income, population density, region and type of area (rural,
suburban, and urban) based on geographic location.
Statin, ACE-I and other medications average and total co-payment during the
adherence period; ACE-I, ARB, statin, beta-blocker, clopidogrel and warfarin use
and all medications use before index date and during the adherence period,
generic and mail order use for index medications.
Primary care physician or specialist visits, cardiologist visits or visits for
cardiovascular testing, influenza vaccination use, length of stay for index MI.
Diabetes, hyperlipidaemia, hypertension, depression, cerebrovascular disease,
chronic heart failure, ischemic heart disease, obesity, chronic renal failure, chronic
obstructive pulmonary disease, atrial fibrillation, metabolic syndrome, peripheral
vascular disease, ventricular arrhythmia, previous diagnostic of coronary arterial
disease.
Symmetry Episode Risk Group® (ERG®) score, Charlson comorbidity score.
Bansilal et al, ESC 2014
26
Adherence Study:
Disposition
1331 excluded
• 29% mental
disorders
• 1%
pregnant/deliv
ery
• 10% Hospice
• 23% Nursing
facility
• 33% ARB fill
during 6
months post
MI
• 4% MI was not
index event
Adults post- MI
1/10/10-2/28/13
N=14,119
Adults post MI with
ACEI and Statin fill
within 6 month post
event
N=7107
7012 (49.6%) No fill of
both ACEI and Statin
during 6 months post
MI
Adults post MI with
ACEI and Statin fill
within 6 month post
event, No exclusion
N=5776
Adults post MI with ACEI
and Statin fill within 6
month post event, No
exclusion, with 6 mth preperiod
1761 without 6
months pre-period
N=4015
Fully-Adherent
(>80%) N=1721
(43%)
Partially-Adherent
(40-79%) N=1031
(31%)
Bansilal et al, ESC 2014
Non-Adherent
(<40%) N=1263
(26%)
27
Adherence Study: Baseline Characteristics
Low
PDC
Mid PDC
High PDC
p value
Age (mean)
Male gender (%)
PDC (mean)
Diabetes (%)
56.6
74.01
21
34.05
57.8
76.72
62
34.20
56.2
79.31
93
25.63
0.0002
0.005
<0.0001
<0.0001
Hyperlipidemia (%)
91.76
94.62
95.41
0.0003
Hypertension (%)
Previous CAD (%)
Previous CVD (%)
Previous PAD (%)
68.19
31.30
5.92
7.57
77.12
34.52
7.21
8.79
68.97
21.50
5.69
5.75
<0.0001
<0.0001
0.215
0.006
Obesity (%)
CHF (%)
CRF (%)
Prospective risk score (ERG) (mean)
4.46
20.66
4.17
2.96
5.78
20.43
5.86
3.29
4.65
17.26
3.78
2.50
0.259
0.033
0.021
<0.0001
Charlson Comorbidity Score (mean)
1.91
2.04
1.82
<0.0001
4.2522
64336
488
4.5701
66058
570
4.0622
66827
592
0.0084
0.031
<0.0001
Length of Stay - Index Admission (mean)
Household income in zip code (median)
Copays for all medications during adherence
period (mean)
Bansilal et al, ESC 2014
28
Adherence Study: Time to MACE
by Adherence Level
Bansilal et al, ESC 2014
29
Adherence Study: Primary Outcome Measures
Event
Low PDC
(N=1031)
Mid PDC
(N=1263)
High PDC PDC group
Ratiop value
(N=1721) comparison
Composite Cardiac Events
18.1 (281)
17.2 (329)
12.8 (328) High v. Low 0.72 0.002
High 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 0.001
High v. Mid 0.59 0.01
Mid v. Low 0.90 0.57
Stroke Hospitalization
1.2 (18)
0.9 (17)
0.6 (16)
0.09
0.86
0.14
0.01
Revascularization Procedures 14.4 (224)
(IP or OP)
13.1 (249)
High v. Low 0.54
High v. Mid 0.94
Mid v. Low 0.58
10.8 (277) High v. Low 0.78
High v. Mid 0.86 0.12
Mid v. Low 0.90 0.30
Bansilal et al, ESC 2014
30
Adherence Study: 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
Bansilal et al, ESC 2014
31
Adherence Study: Conclusions
• High levels of adherence to guideline recommended
therapies are associated with a lower rate of major
cardiovascular events compared to partial or nonadherence.
• 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.
Bansilal et al, ESC 2014
32