FULL COVERAGE FOR PREVENTIVE MEDICATIONS AFTER MYOCARDIAL INFARCTIONNEW ENGLAND JOURNAL OF MEDICINE 2011; DOI: 10.1056/NEJMSA1107913

Niteesh K. Choudhry, MD, PhD,1 Jerry Avorn, MD,1 Robert J. Glynn, ScD, PhD,1,2 Elliott M. Antman, MD,3 Sebastian Schneeweiss, MD, ScD1, Michele Toscano, MS,4 Lonny Reisman, MD,4 Joaquim Fernandes, MS,4 Claire Spettell, PhD,4 Joy L. Lee, MS,1 Raisa Levin, MS,1 Troyen Brennan, MD, JD, MPH,5 and William H. Shrank, MD, MSHS,1 for the Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) Trial

Divisions of 1Pharmacoepidemiology and Pharmacoeconomics and 2Preventive Medicine, and the 3Cardiovascular Division, Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School; 4Aetna and 5CVS Caremark

Background Adherence to evidence-based medications prescribed after

myocardial infarction (MI) remains poor■Within 2 years of initiating therapy, only half of patients are adherent to their

prescribed statins, beta-blockers, or ACEI/ARBs

Drug costs appear to be a central reason for medication underuse■Even among patients with insurance, utilization varies according to the

comprehensiveness of coverage

Eliminating out-of-pocket costs for evidence-based therapies may promote adherence and improve outcomes■Referred to as “value-based insurance design” or “evidence-based plan design”■Observational studies support the ability of this strategy to increase adherence but

its impact on health outcomes and spending has not been rigorously evaluated

Post-Myocardial Infarction Free Rx Event and Economic Evaluation (MI FREEE) Trial

OBJECTIVE:

To evaluate the impact of eliminating copayments for statins, beta-blockers and ACEI/ARB prescribed to post-MI

patients on rates of major vascular events and health spending

clinicaltrials.gov NCT00566774

Overall DesignMI FREEE

EXCLUSIONS:Age > 65, didn’t have both

drug and medical coverage, enrolled in ineligible plan

AETNA BENEFICIARIES DISCHARGED AFTER ACUTE MIBased on discharge claims submitted by hospitals (specificity 99%)

cluster randomizedby plan sponsor

CONTROLusual levels of prescription

insurance coverage

FULL COVERAGEall beta-blockers, ACEI/ARBs

and statins

Both groups contacted to tell them that taking their prescribed medications is important +/- inform them of their benefit change

SOURCE: Choudhry et al. Am Heart J 2008; 156: 31

study group assignment

occurred a mean of 49 days post-MI

Outcomes and analysisMI FREEE

Outcomes assessed using validated health services claims and based on intention to treat principles■Included only verifiable (in hospital) fatal events

Clinical events evaluated using time-to-event (Cox) modeling; adherence and spending evaluated using generalized estimating equations■Analyses adjusted for the cluster and block randomized design

Primary First major vascular event* or revascularization

Secondary Total major vascular events and revascularization

First major vascular event

Medication adherence (proportion of days covered)

Pharmacy and medical spending

*Fatal or non-fatal acute MI, unstable angina, stroke, congestive heart failure

5,855 patients (2,980 plan sponsors) randomized

FULL COVERAGE2,845 patients (1,494 plan sponsors)

USUAL COVERAGE3,010 patients (1,486 plan sponsors)

913 covered by plan sponsors who declined to participate

6,768 patients (3,983 plan sponsors) potentially eligible

133 (4.7%) patients lost insurance eligibility before randomization

151 (5.0%) patients lost insurance eligibility before randomization

Enrollment and RandomizationMI FREEE

Median follow-up: 394 days (interquartile range: 201 to 663 days)

CHARACTERISTICFULL

COVERAGE(N=2845)

USUAL COVERAGE

(N=3010)Age, mean 53.6 53.7Male sex, % 75.6 74.7Comorbidities, %

Congestive heart failure 27.0 29.1Diabetes 34.3 34.8Hypertension 71.2 72.4Prior MI 15.6 17.4Stroke 5.8 6.7

Procedures on index hospitalization, %Angiography 94.7 93.7PCI 67.3 66.0CABG 17.9 18.1

Monthly baseline copayment, meanACEI/ARB $13.48 $13.35Beta-blocker $12.64 $12.83Statin $24.98 $24.92

Baseline characteristics (selected)*

MI FREEE

*There was no significant between-group difference in any category

0

10

20

30

40

27.730.7

38.6

12.1

22.9 25.2

31.6

8.9% f

ully

ad

he

ren

t

0

10

20

30

40

50

60

41.1

49.355.1

43.9

35.9

45.049.0

38.9

% o

f d

ay

s c

ov

ere

dMedication adherenceMI FREEE

6.2%4.4%5.6% 5.4%

37%32% 31% 41%

P<0.001 for all comparisons

Full coverage Usual coverage

ACEI/ARBs Beta-blockers Statins All 3 classes

Hazard ratio (95% CI): 0.93 (0.82-1.04)P-value: 0.21

Full coverage

Usual coverage

Rate per 100 person years 17.6 18.8

No. at RiskUsual coverageFull coverage

3010 2361 10991652 662 379 1312845 2295 1572 1013 625 340 135

Full coverage

Usual coverage

Major vascular event or revascularizationMI FREEE

Hazard ratio (95% CI): 0.86 (0.74-0.99)P-value: 0.03

Full coverage

Usual coverage

Rate per 100 person years 11.0 12.8

Full coverage

Usual coverage

Major vascular events (Fatal or nonfatal MI, unstable angina, CHF, stroke)

MI FREEE

No. at RiskUsual coverageFull coverage

3010 2361 10991652 662 379 1312845 2295 1572 1013 625 340 135

Full Coverage Usual Coverage0

5

10

15

20

25

21.523.3

Rat

e p

er 1

00

per

son

yea

r

Total major vascular events or revascularization*

MI FREEE

Hazard ratio (95% CI) 0.89 (0.80-0.99)

P=0.03

*Considers all events experienced by each patient

$0

$500

$1,000

$1,500

$2,000

$802

$480

$1,282$1,164

$618

$1,781

Pa

tie

nt

Sp

en

din

gHealth spendingMI FREEE

$0

$25,000

$50,000

$75,000

$5,649

$60,358$66,008

$5,085

$66,693$71,778

To

tal s

pe

nd

ing

30%P<0.001

18%P=0.005

26%P<0.001

17%P=0.02

10%P=0.72

11%P=0.68

Full coverage Usual coverage

Pharmacy Medical Total

$0

$200

$400

$600

$800

$1,000

$323 $203

$526

$665

$235

$900

Pa

tie

nt

Sp

en

din

gCardiovascular spendingMI FREEE

$0

$5,000

$10,000

$15,000

$20,000

$25,000

$2,594

$15,661$18,254

$2,488

$17,750$20,238

To

tal s

pe

nd

ing

51%P<0.001

9%P=0.05

40%P<0.001

8%P=0.02

14%P=0.06

11%P=0.08

Full coverage Usual coverage

Pharmacy Medical Total

SummaryMI FREEE

Eliminating copayments for post-MI secondary prevention: Improved adherence Reduced rates of major vascular events*

Reduced patient out-of-pocket spending for drugs and other non-drug services

Did not increase insurer or total spending Did not significantly reduce the composite outcome of major

vascular events plus revascularization

*Fatal or non-fatal acute MI, unstable angina, stroke, congestive heart failure

ImplicationsMI FREEE

This quality-improvement strategy could contribute to ongoing efforts to improve post-MI outcomes■Probably cost-effective■Could be easily scaled

Adherence was improved but remained poor even for patients who received full coverage■Average adherence to all 3 of the study medication classes remained < 50%

Our results highlight the need for other interventions to promote adherence■Should target other causes of non-adherence: complex treatment regimens,

difficulties accessing medications, knowledge gaps, adverse effects, forgetfulness

Choudhry NK et al. New England Journal of Medicine 2011; DOI: 10.1056/NEJMsa1107913