Published
16 October 2008, doi:10.1136/bmj.a1840
Cite this as: BMJ
2008;337:a1840
Research
The
prevention of progression of arterial
disease and diabetes (POPADAD) trial:
factorial randomised placebo controlled
trial of aspirin and antioxidants in
patients with diabetes and asymptomatic
peripheral arterial disease
Jill Belch,
professor of vascular medicine1,
Angus MacCuish,
consultant diabetologist2,
Iain Campbell,
professor of diabetic medicine3,
Stuart Cobbe,
Walton professor of cardiology4,
Roy Taylor,
professor of medicine and metabolism5,
Robin Prescott,
professor of health technology
assessment8,
Robert Lee, research
associate8,
Jean Bancroft, senior
research nurse1,
Shirley MacEwan,
honorary senior research fellow1,
James Shepherd,
professor of pathological
biochemistry6,
Peter Macfarlane,
professor of electrocardiology7,
Andrew Morris,
professor of diabetic medicine9,
Roland Jung,
consultant physician (endocrine and
diabetes) and honorary professor of
medicine10,
Christopher Kelly,
consultant diabetologist11,
Alan Connacher,
consultant diabetologist and
endocrinologist12,
Norman Peden,
consultant diabetologist13,
Andrew Jamieson,
consultant physician14,
David Matthews,
consultant physician15,
Graeme Leese,
consultant endocrinologist,
John McKnight,
consultant physician and honorary
senior lecturer16,
Iain O’Brien,
consultant diabetologist17,
Colin Semple,
consultant physician18,
John Petrie,
reader in diabetes9,
Derek Gordon,
consultant physician19,
Stuart Pringle,
professor of cardiology20,
Ron MacWalter,
consultant stroke physician1,
Prevention of Progression of
Arterial Disease and Diabetes Study
Group, Diabetes Registry Group, and
Royal College of Physicians
Edinburgh
1
Institute of Cardiovascular Research,
University of Dundee, Ninewells
Hospital, Dundee DD1 9SY, 2
Diabetes Centre, Glasgow Royal Infirmary,
3 Department of Medicine,
Royal Victoria Hospital, Kirkcaldy,
4 British Heart Foundation Glasgow
Cardiovascular Research Centre,
University of Glasgow, 5
Royal Victoria Infirmary, Newcastle upon
Tyne, 6 Department of
Biochemistry, Glasgow Royal Infirmary,
7 Department of Medical
Cardiology, Glasgow Royal Infirmary,
8 Medical Statistics Unit,
University of Edinburgh, 9
Diabetes Research Centre, Ninewells
Hospital, 10 Diabetes and
Endocrinology, Ninewells Hospital,
11 Diabetes Centre, Stirling Royal
Infirmary, 12 Diabetes
Centre, Perth Royal Infirmary, 13
Diabetes Centre, Falkirk and District
Royal Infirmary, Falkirk, 14
Diabetes Centre, Queen Margaret
Hospital, Dunfermline, 15
Diabetes Centre, Monklands Hospital,
Airdrie, 16 Metabolic Unit,
Western General Hospital, Edinburgh,
17 Wishaw General Hospital,
Wishaw, 18 Southern General
Hospital NHS Trust, Glasgow, 19
Medical Unit B, Stobhill NHS Trust,
Glasgow, 20 Cardiology
Department, Ninewells Hospital
Objective To determine whether
aspirin and antioxidant therapy,
combined or alone, are more
effective than placebo in reducing
the development of cardiovascular
events in patients with diabetes
mellitus and asymptomatic
peripheral arterial disease.
Design
Multicentre, randomised, double blind,
2x2 factorial, placebo
controlled trial.
Setting
16 hospital centres in Scotland,
supported by 188 primary care
groups.
Participants 1276 adults aged 40 or
more with type 1 or type 2
diabetes and an ankle brachial pressure
index of 0.99 or less but no
symptomatic cardiovascular disease.
Interventions Daily, 100 mg aspirin
tablet plus antioxidant
capsule (n=320), aspirin tablet plus
placebo capsule (n=318),
placebo tablet plus antioxidant capsule
(n=320), or placebo tablet
plus placebo capsule (n=318).
Main
outcome measures Two hierarchical
composite primary end points
of death from coronary heart disease or
stroke, non-fatal myocardial
infarction or stroke, or amputation
above the ankle for critical
limb ischaemia; and death from coronary
heart disease or stroke.
Results
No evidence was
found of any interaction between aspirin
and antioxidant. Overall,
116 of 638 primary events occurred
in the aspirin groups compared
with 117 of 638 in the no aspirin
groups (18.2% v 18.3%):
hazard ratio 0.98 (95% confidence
interval 0.76 to 1.26). Forty
three deaths from coronary heart disease
or stroke occurred in the aspirin
groups compared with 35 in
the no aspirin groups (6.7% v
5.5%): 1.23 (0.79 to 1.93). Among
the antioxidant groups 117 of 640
(18.3%) primary events occurred
compared with 116 of 636 (18.2%)
in the no antioxidant groups
(1.03, 0.79 to 1.33). Forty two (6.6%)
deaths from coronary heart
disease or stroke occurred in the
antioxidant groups compared
with 36 (5.7%) in the no antioxidant
groups (1.21, 0.78 to 1.89).
Conclusion
This trial does not provide evidence to
support the use of aspirin or
antioxidants in primary prevention of
cardiovascular events and
mortality in the population with
diabetes studied.
Trial
registration Current Controlled
Trials ISRCTN53295293
[controlled-trials.com]
.
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