The ADDITION-Europe study

Simon Griffin, Knut Borch-Johnsen, Melanie Davies, Kamlesh Khunti, Guy Rutten, Annelli Sandbæk, Stephen Sharp, Rebecca Simmons,

Maureen van den Donk, Nicholas Wareham, Torsten Lauritzen

Netherlands

Denmark

UK

www.addition.au.dk

Background

• Type 2 diabetes is common, costly and associated with a significant

burden of morbidity and mortality

• Single risk factor interventions can reduce risk of complications

• Intensive multifactorial treatment can halve the risk of CVD in

people with longstanding diabetes

• The effectiveness of multifactorial treatment in people with screen

detected diabetes is unknown

Diabetes detectablebiochemically

Diabetes detectableclinically

0 years ~8 years

Diabetes detectedby screening

~4 years

If we find and treat people earlier, canwe reduce the chance of them dying early

and/or suffering from heart attacks and strokes?

Background

Background

The ADDITION-Europe study

• involves individuals at an earlier stage, i.e. screen detected

diabetes

• is set in daily clinical practice in primary care

• assesses effectiveness of multifactorial treatment

• is randomised at the general practice level

• is pragmatic in design

Five-year data collection

161 practices provided intensive treatment

Participants: 1,678

156 practices provided routine care

Participants: 1,379

Follow-up1,678 (100%) with endpoint data104 (6.2%) died

Of those alive1,352 (86%) measured at CRF1,532 (97%) laboratory data collected

Follow-up1,377 (99.9%) with endpoint data92 (6.7%) died

Of those alive1,048 (81%) measured at CRF1,241 (96%) laboratory data collected

Prescribed treatment at baseline

Routine careIntensive treatment

0

10

20

30

40

50

60

70

80

90

100

% o

f part

icip

an

ts p

resc

ribed

medic

ati

on

StatinsBP-lowering Glucose-lowering

Baseline Baseline Baseline Baseline Baseline Baseline

Prescribed treatment at baseline and follow-up

0

10

20

30

40

50

60

70

80

90

100

% o

f part

icip

an

ts p

resc

ribed

medic

ati

on

Routine careIntensive treatment

Baseline Followup

Baseline Followup

Baseline Baseline Baseline Baseline

StatinsBP-lowering Glucose-lowering

Prescribed treatment at baseline and follow-up

0

10

20

30

40

50

60

70

80

90

100

% o

f part

icip

an

ts p

resc

ribed

medic

ati

on

Routine careIntensive treatment

Baseline Followup

Baseline Followup

Baseline Followup

Baseline Followup

Baseline Baseline

StatinsBP-lowering Glucose-lowering

Prescribed treatment at baseline and follow-up

0

10

20

30

40

50

60

70

80

90

100

% o

f part

icip

an

ts p

resc

ribed

medic

ati

on

Routine careIntensive treatment

Baseline Followup

Baseline Followup

Baseline Followup

Baseline Followup

Baseline Followup

Baseline Followup

StatinsBP-lowering Glucose-lowering

Relative risk of composite CVD endpoint as a first event

0.1 0.2 0.5 1 2

Favours intensive treatment Favours routine care

Overall(I-squared = 0.0%)

Netherlands

Denmark

UK

Country

0.83 (0.65 to 1.05)

0.96 (0.45 to 2.03)

0.83 (0.59 to 1.16)

0.80 (0.55 to 1.17)

Hazard Ratio (95% CI)

Cumulative probability of composite CVD endpoint

0

2

4

6

8

10

12

14

Pri

mary

com

posit

e e

nd

poin

t (%

)

0 1 2 3 4 5 6 7Years of follow-up

1377 1354 1321 1278 1093 879 535 138RCIT 1678 1654 1622 1564 1348 1058 624 208

Number at risk

p=0.12Routine careIntensive treatment

• Multifactorial intensive treatment was not associated with increased risk of mortality

• Mortality in both groups was low

Results in context

0

2

4

6

8

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14

All-c

au

se m

ort

ality

(%

)

0 1 2 3 4 5 6 7Years of follow-up

ADDITION Routine care

Danish general registry: Carstensen et al. Diabetologia 2008;51:2187-2196

Danish population with diabetes

Danish general population

Conclusions

• Cardiovascular risk factors improved in both groups in the five years following detection by screening

• The intervention to promote intensive management was associated with statistically significant but modest differences in prescribed treatment and levels of cardiovascular risk factors

• These differences were associated with a non-statistically significant 17% relative reduction in the incidence of a composite cardiovascular event endpoint over five years

ADDITION-Europe study team

ADDITION study teams

• ADDITION-Denmark study group includes Bendix Carstensen, Else-Marie Dalsgaard, Ynna Nielsen,

Søren Bech-Morsing, Mette Vinther Skriver, Helle Terkildsen, Morten Charles, Merete Frandsen,

Toke Bek and Henrik Andersen

• ADDITION-Cambridge study group includes Amanda Adler, Judith Argles, Gisela Baker, Rebecca Bale,

Roslyn Barling, Daniel Barnes, Mark Betts, Sue Boase, Ryan Butler, Parinya Chamnan, Sean Dinneen,

Pesheya Doubleday, Mark Evans, Tom Fanshawe, Francis Finucane, Philippa Gash, Julie Grant, Wendy

Hardeman, Robert Henderson, Garry King, Ann-Louise Kinmonth, Joanna Mitchell,

Richard Parker, Nicola Popplewell, A. Toby Prevost, Lincoln Sargeant, Megan Smith, Stephen Sutton,

Fiona Whittle and Kate Williams.

• ADDITION-Netherlands study group includes Kees Gorter, Paul Janssen, Lidian Izeboud, Jacqueline

Berends, Marlies Blijleven, Bart Thoolen, Denise de Ridder, Jozien Bensing, Mehmet Akarsubasi, Paula

Koekkoek, Carla Ruis, Geert Jan Biessels, Jaap Kappelle and Michiel van der Linden.

• ADDITION-Leicester study group includes Balasubramanian Thiagarajan Srinivasan, David Webb,

Laura J Gray, Mary Quinn, Emma Wilmot, Samiul A Mostafa, Nitin Gholap, Hamid Mani,

Winston Crasto, Steve Hiles, Joe Henson, Nick Taub, Janet Jarvis, Sukhjit Sehmi, Fiona Ablett, Champa

Merry, Emma Healey, Julia Stockman, Sandra Campbell, Janette Barnett, Nil Radia,

Mo Radia, Jo Howe, Lesley Bryan, Jane Brela, Jayne Hill, Helen Bray, Rachel Plummer, Zubeir Essat and

Francis Pullen