International comparison of outcomes among 140 887 survivors after acute myocardial infarction: real-world evidence from electronic health and administrative

International comparison of outcomes among 140 887 survivors after

acute myocardial infarction: real-world evidence from electronic health and

administrative records

Professor Harry Hemingway

on behalf of the APOLLO investigators

European Society of Cardiology Congress 2014Registry Hot Line Session: Atrial fibrillation and myocardial infarction

Authors

Eleni Rapsomaniki1, Magnus Janzon2, David J. Cohen3, Tomas Jernberg4, Nicholas Moore5, Marcus Thuresson6, Erru Yang7, Patrick Blin5, Saga Johansson8, Harry Hemingway1

1Farr Institute of Health Informatics Research, University College London, UK2Linkoping University, Sweden3Saint Luke’s Mid America Heart Institute, Kansas City, USA4Karolinska University Hospital, Sweden5Department of Pharmacoepidemiology, University of Bordeaux, France6Statisticon AB, Uppsala, Sweden7Health Economics & Epidemiology, Evidera, Lexington, USA8Observational Research Center, AstraZeneca R&D, Mölndal, Sweden

Conflicts

AstraZeneca funded the APOLLO Programme alongside the PEGASUS-TIMI 54 study which is aimed at determining the clinical efficacy and safety of long-term dual antiplatelet therapy with ticagrelor plus aspirin for the prevention of secondary cardiovascular events in patients with a recent myocardial infarction and additional atherothrombotic risk factors

Motivation

• Importance – MI survivors

– International comparisons

• Uncertainty– Unselected populations

– Long-term follow-up

– Non-fatal and fatal

– Benefits and harms

• Novel opportunity – Electronic health and administrative records

Objective

• To compare atherothrombotic events, death and bleeding risks in 1-year post-MI survivors across Sweden, the USA, England and France over 3 years of follow-up

Methods: electronic health records and administrative data sources in APOLLO

Programme

Countries

Record sources

Details

CPRD, Clinical Practice Research Datalink; EGB, Echantillon Généraliste des Bénéficiaires; HES, Hospital Episodes Statistics; MINAP, Myocardial Ischaemia National Audit Project; PMSI, Programme de médicalisation des systèmes d'information

EGB,PMSI

• Sample of national healthcare insurance data

• Hospital discharge data linked to death registry

France

National registries

• Nationwide• Longitudinal

data• Hospital

discharge data linked to prescribed data register and death registry

Sweden

CPRD, MINAP, HES

• Four linked datasets

• Longitudinal data

• Primary and secondary care, and disease registry and death registry

England

Medicare

• Age >65 years• Demographics

and health insurance claims

• Linked to death registry

USA

Methods: study population, disease definitions and statistics

• Patients entered the study 1 year after the most recent discharge for MI (study period: 2002–2011)

• Disease definitions were harmonised using ICD9/ICD10 diagnostic codes

• Data from each country were analysed using a common protocol

• Cox models were utilised to estimate adjusted risks and relative risks, using Sweden as reference

ICD, International Classification of Diseases

Age- and sex-standardised prevalence of comorbidities and secondary prevention treatments

ACEI, angiotensin-converting enzyme inhibitor; ADP, adenosine diphosphate; ARB, angiotensin receptor blocker; CABG, coronary artery bypass graft; COPD, chronic obstructive pulmonary disease; MI, myocardial infarction; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention

Baseline comorbidities (%) Treatments prescribed at 1 year post-MI (%)

Revascularisation (%)

Hypertension

History ofheart failure

Diabetes

History of atrial fibrillation

History of >1 MI

History of cancer

History of stroke

History of COPD

History ofhospitalised bleeding

History of renal disease

History of PAD

Sweden, n=77 798

USA, n=53 909

England, n=7238

France, n=1764

0 20 40 60 80 100Percentage

PCI

CABG

0 20 40 60 80Percentage

Statins

b-blockers

ACEI/ARBs

Aspirin

ADP-receptor blockers

Dualantiplatelet

Vitamin K antagonists

0 20 40 60 100Percentage

80

54.9%48.1%

38.7%61.6%

14.1%19.7%

11.4%7.1%

9.8%8.4%8.9%

54.4%41.0%

22.9%

65.0%49.7%

26.4%

80.4%86.7%

76.1%

73.5%68.5%

81.3%

71.3%80.1%

71.4%

80.0%79.4%

82.3%

63.9%79.0%

69.1%68.7%

29.0%40.7%

24.2%29.6%

25.4%38.5%

23.2%28.0%

22.0%24.2%

20.8%16.9%

14.4%11.7%12.2%13.5%

0.4%7.2%

10.5%4.2%

7.8%7.8%

11.2%5.4%

13.0%7.9%8.0%

15.2%

11.3%6.4%

8.3%3.7%

10.8%28.6%

11.9%11.2%

9.1%16.1%

7.5%3.8%

Prognostic validity:adjusted HRs of all-cause death

CABG, coronary artery bypass graft; CI, confidence interval; HR, hazard ratio; PCI, percutaneous coronary intervention

SwedenUSAEnglandFranceOverall mean

CABG, no vs yes


Age per 10 years


PCI, no vs yes


History of renal disease


History of heart failure

0.5 1 2 3 4 5 6

HR

Number ofevents

% in study

15 23322 498

659222

12.616.910.45.6

15 23322 498

659222

15 23322 498

659222

55.842.941.865.0

15 23322 498

659222

5.03.47.06.9

15 23322 498

659222

27.745.021.023.2

HR 95% CI

1.672.212.001.751.92

(1.58–1.78)(2.12–2.31)(1.42–2.83)(0.95–3.22)(1.54–2.40)

2.151.791.691.791.85

(2.11–2.20)(1.75–1.82)(1.55–1.84)(1.57–2.04)(1.63–2.11)

1.901.711.871.851.81

(1.83–1.98)(1.65–1.76)(1.50–2.32)(1.39–2.46)(1.66–1.98)

1.851.561.921.761.73

(1.72–1.92)(1.50–1.62)(1.57–2.34)(1.22–2.54)(1.53–1.96)

1.681.721.561.451.70

(1.63–1.74)(1.67–1.77)(1.32–1.85)(1.07–1.06)(1.66–1.74)

3-year cumulative absolute risks

Shaded areas correspond to 95% confidence intervalsMI, myocardial infarction

All-cause death MI/stroke/all-cause death

Follow-up (years)

Observed risk (%)

Adjusted risk (%)

Observed risk (%)

Adjusted risk (%)

Follow-up (years)

Follow-up (years)

50

40

30

20

10

0

0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.0 0.5 1.0 1.5 2.0 2.5 3.0

50

40

30

20

10

0

Sweden 20.1 (19.7–20.4)USA 30.2 (29.8–30.7)England 13.7 (12.6–14.8)France 14.3 (12.5–16.1)


Follow-up (years)0.0 0.5 1.0 1.5 2.0 2.5 3.0 0.0 0.5 1.0 1.5 2.0 2.5 3.0

20

15

10

5

0

30

25

20

15

10

5

0



Relative risks vs Sweden

aComorbidities adjusted for history of >1 MI, hypertension, renal disease, heart failure, PAD, stroke, atrial fibrillation, hospitalised bleeding, cancer and COPD. French group adjusted only for age, sex, and year of index MI. All models were additionally adjusted for year of index MICABG, coronary artery bypass graft; CI, confidence interval; COPD, chronic obstructive pulmonary disease; KM, Kaplan–Meier; MI, myocardial infarction; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention; RR, relative risk

RRRR

All-cause death MI/stroke/all-cause death

1.55

RR 95% CI RR 95% CI

1.46

1.111.17

0.77

1.04

1.040.90

0.69

1.14

1.111.09

(1.50–1.61)

(1.39–1.53)

(1.05–1.18)(1.11–1.24)

(0.66–0.90)

(0.86–1.26)

(0.85–1.28)(0.73–1.12)

(0.56–0.84)

(0.93–1.41)

(0.88–1.39)(0.86–1.37)

1.33

1.09

0.830.88

0.89

1.12

1.121.04

0.60

0.83

0.820.78

(1.29–1.37)

(1.05–1.13)

(0.80–0.87)(0.84–0.92)

(0.79–1.00)

(0.98–1.28)

(0.98–1.30)(0.90–1.20)

(0.50–0.72)

(0.70–0.99)

(0.68–0.98)(0.64–0.94)

0.75 1 1.5 0.75 1 1.5

Unadjusted (KM)

Age and sex

+ comorbiditiesa

+ PCI/CABG

USA

Unadjusted (KM)

Age and sex

+ comorbiditiesa

+ PCI/CABG

England

Unadjusted (KM)

Age and sex

+ comorbiditiesa

+ PCI/CABG

France

3-year cumulative risks of hospitalised bleeding events

Shaded areas correspond to 95% CIsaComorbidities adjusted for history of >1 MI, hypertension, renal disease, heart failure, PAD, stroke, atrial fibrillation, hospitalised bleeding, cancer and COPD. French group adjusted only for age, sex, and year of index MI. All models additionally adjusted for year of index MICABG, coronary artery bypass graft; CI, confidence interval; COPD, chronic obstructive pulmonary disease; KM, Kaplan–Meier; MI, myocardial infarction; PAD, peripheral arterial disease; PCI, percutaneous coronary intervention; RR, relative risk

Adjusted risk (%)

Follow-up (years)Follow-up (years)

Observed risk (%) RR (vs Sweden)

RR

0.0

6

0.5 1.0 1.5 2.0 2.5 3.0

5

4

3

2

1

0

0.0

6

0.5 1.0 1.5 2.0 2.5 3.0

5

4

3

2

1

0



RR 95% CI

Unadjusted (KM)Age and sex+ comorbiditiesa

+ PCI/CABG

USA2.122.141.641.69

(1.92–2.34)(1.92–2.38)(1.45–1.84)(1.51–1.90)


+ PCI/CABG

England1.352.071.941.94

(0.91–2.01)(1.40–3.07)(1.28–2.93)(1.28–2.93)


+ PCI/CABG

France0.750.991.061.06

(0.42–1.33)(0.58–1.69)(0.62–1.81)(0.62–1.81)

0.5 1 2

Limitations

• Medication information– Lacking for USA

• Data on cause-specific mortality– Lacking for USA, France

• Socioeconomic data– Lacking for Sweden, USA, France

• Patient age– USA >65 years only

Main results summary

• Among 140 887 1-year post-MI survivors drawn from unselected electronic health and administrative records populations:– High-risk state (>3% annual all-cause death risk1,2)

– About half of deaths are non-cardiovascular

– Compared with European populations, US patients had • higher (age and sex-standardised) prevalence of comorbidities

• higher adjusted all-cause mortality

– Risk of further MI, stroke or death remained high (about 1 in 5) across the 3 years and across the 4 countries studied, with fairly constant annual risks

– Difference in risk of hospitalised bleeding in the USA and England vs Sweden remained substantial

1Montalescot G et al. Eur Heart J 2013;34:2949–30032Fihn SD et al. J Am Coll Cardiol 2012;60:e44–e164

Clinical implications

• Guidelines1,2

– Definition of ‘high risk’ needs to be considered

• Policy– Impetus to improve quality of healthcare systems

• Primary care– Need for a generalist approach

• Evidence for regulators and clinicians– New interventions and generalisability of trial results

• National electronic health record resources– Quality, scope and comparability

1Montalescot G et al. Eur Heart J 2013;34:2949–30032Fihn SD et al. J Am Coll Cardiol 2012;60:e44–e164

Acknowledgements

• Editorial support was provided by Oxford PharmaGenesis™ Ltd

Documents

International comparison of outcomes among 140 887 survivors after acute myocardial infarction: real-world evidence from electronic health and administrative