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

Published on Oct 16, 2008in BMJ30.223
· DOI :10.1136/BMJ.A1840
Jill J. F. Belch78
Estimated H-index: 78
(Dund.: University of Dundee),
Angus MacCuish2
Estimated H-index: 2
+ 23 AuthorsRon MacWalter8
Estimated H-index: 8
(Dund.: University of Dundee)
Sources
Abstract
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, 2×2 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][1]. [1]: /external-ref?link_type=ISRCTN&access_num=ISRCTN53295293
Figures & Tables
Download
📖 Papers frequently viewed together
5,695 Citations
6,065 Citations
5,767 Citations
References45
Newest
#1Jill J. F. BelchH-Index: 78
#2Eric J. TopolH-Index: 223
Last. Frank SullivanH-Index: 50
view all 16 authors...
HIS CALL-TO-ACTION document is an initiative of the Prevention of Atherothrombotic Disease Network, an international, multidisciplinary network, adjoined by the mutual goal of increasing awareness, detection, and treatment rates of peripheral arterial disease (PAD) and increasing awareness of the interrelationship between PAD and the risk of ischemic events. Although the prevalence of PAD in Europe and North America is estimated at approximately 27 million people, PAD remains a largely underdiag...
44 Citations
#1Trisha Greenhalgh (UCL: University College London)H-Index: 108
#2Gary W. Wood (UCL: University College London)H-Index: 3
Last. Sue HinderH-Index: 19
view all 5 authors...
Objective To document the views of patients and the public towards the summary care record (SCR, a centrally stored medical record drawn from the general practice record) and HealthSpace (a personal health organiser accessible through the internet from which people can view their SCR), with a particular focus on those with low health literacy, potentially stigmatising conditions, or difficulties accessing health care. Design 103 semistructured individual interviews and seven focus groups. Settin...
121 CitationsSource
‘Three can keep a secret, if two of them are dead.’ (Benjamin Franklin) ‘Whoever wishes to keep a secret must hide the fact that he possesses one.’ (Johann Wolfgang von Goethe) ‘If you reveal your secrets to the wind you should not blame the wind for revealing them to the trees.’ (Kahlil Gibran) Our village postman used to start a rumour at the first house of his delivery and see if he could beat the rumour to the end of his round. Medical gossip had a special cachet that proved unbeatable. One ...
11 CitationsSource
#1Khin Than Win (UOW: University of Wollongong)H-Index: 16
#2John Fulcher (UOW: University of Wollongong)H-Index: 13
Electronic health record (EHR) systems are now in widespread use in healthcare institutions worldwide. EHRs include sensitive health information and if they are integrated among healthcare providers, data can be accessible from many different sources. This leads to increased concern regarding invasion of privacy and confidentiality. Incorporating consent mechanisms into EHRs has the potential to enhance confidentiality. However there are both positive and negative effects from employing such mec...
40 CitationsSource
#1Lars NorgrenH-Index: 61
#2William R. HiattH-Index: 96
Last. Robert B. RutherfordH-Index: 26
view all 7 authors...
603 Citations
#1Lars NorgrenH-Index: 61
#2William R. Hiatt (University of Colorado Denver)H-Index: 96
Last. F. G. R. FowkesH-Index: 59
view all 6 authors...
The Trans-Atlantic Inter-Society Consensus Document on Management of Peripheral Arterial Disease (TASC) was published in January 2000 as a result of cooperation between fourteen medical and surgical vascular, cardiovascular, vascular radiology and cardiology societies in Europe and North America. This comprehensive document had a major impact on vascular care amongst specialists. In subsequent years, the field has progressed with the publication of the CoCaLis document and the American College o...
5,912 CitationsSource
#1John B. Buse (UNC: University of North Carolina at Chapel Hill)H-Index: 118
#2Henry N. Ginsberg (Columbia University)H-Index: 118
Last. Neil J. Stone (NU: Northwestern University)H-Index: 56
view all 16 authors...
The American Heart Association (AHA) and the American Diabetes Association (ADA) have each published guidelines for cardiovascular disease prevention: the ADA has issued separate recommendations for each of the cardiovascular risk factors in patients with diabetes, and the AHA has shaped primary and secondary guidelines that extend to patients with diabetes. This statement will attempt to harmonize the recommendations of both organizations where possible but will recognize areas in which AHA and...
1,010 CitationsSource
#1Alan T. HirschH-Index: 76
#2Ziv J. HaskalH-Index: 58
Last. Barbara RiegelH-Index: 107
view all 30 authors...
2,997 CitationsSource
#1Barbara V. HowardH-Index: 129
#2Lyle G. Best (UND: University of North Dakota)H-Index: 10
Last. Richard B. Devereux (Cornell University)H-Index: 167
view all 9 authors...
OBJECTIVE —Diabetes has been defined as a coronary heart disease (CHD) risk equivalent, and more aggressive treatment goals have been proposed for diabetic patients. RESEARCH DESIGN AND METHODS —We studied the influence of single and multiple risk factors on the 10-year cumulative incidence of fatal and nonfatal CHD and cardiovascular disease (CVD) in diabetic and nondiabetic men and women, with and without baseline CHD or CVD, in a population ( n = 4,549) with a high prevalence of diabetes. RES...
148 CitationsSource
The Joint British Societies’ guidelines (JBS 2) on cardiovascular disease prevention in clinical practice were developed by a Working Party (see table) with nominated representatives from six professional societies. All members contributed to the text and those from the specialist societies of hypertension, lipids, and diabetes were specifically responsible for developing the sections on blood pressure, lipids, and glucose. All sections of the document represent an evidence based consensus by al...
878 CitationsSource
Cited By735
Newest
#1Larry B. GoldsteinH-Index: 95
#2Sudha SeshadriH-Index: 114
Last. Ralph L. SaccoH-Index: 157
view all 3 authors...
Source
#1Ella Murphy (National University of Ireland, Galway)
#2James M. G. Curneen (National University of Ireland, Galway)
Last. John W. McEvoy (National University of Ireland, Galway)H-Index: 29
view all 3 authors...
Aspirin’s antithrombotic effects have a long-established place in the prevention of cardiovascular disease (CVD), and its traditional use as a core therapy for secondary prevention of CVD is well recognized. However, with the advent of newer antiplatelet agents and an increasing understanding of aspirin’s bleeding risks, its role across the full spectrum of modern CVD prevention has become less certain. As a consequence, recent trials have begun investigating aspirin-free strategies in secondary...
Source
#1Sian Bradley (UNSW: University of New South Wales)H-Index: 4
#2Kevin Spring (UNSW: University of New South Wales)H-Index: 31
view all 6 authors...
The increasing prevalence of diabetes and stroke is a major global public health concern. Specifically, acute stroke patients, with pre-existing diabetes, pose a clinical challenge. It is established that diabetes is associated with a worse prognosis after acute stroke and the various biological factors that mediate poor recovery profiles in diabetic patients is unknown. The level of association and impact of diabetes, in the setting of reperfusion therapy, is yet to be determined. This article ...
Source
#1Ilaria CavallariH-Index: 13
Last. Francesco GrigioniH-Index: 4
view all 8 authors...
Source
#1Yinong Chen (PKU: Peking University)
#2Chun Yin (CQMU: Chongqing Medical University)
Last. Yihong Sun (China-Japan Friendship Hospital)
view all 7 authors...
Background: The value of aspirin for primary prevention continues to be debated. Data showing whether aspirin use for primary prevention adheres to established guidelines in real world practice are sparse. Methods: A total of 13,104 patients without cardiovascular diseases (CVD) were selected from the DYS-lipidemia International Study of China, a national survey of patients with dyslipidemia in 2012. The CVD risk of the participants were calculated using the 10-year risk of Ischemic Cardiovascul...
Source
#2Qing Gu (Peking Union Medical College Hospital)
Last. Rong Wang
view all 5 authors...
Objectives: A meta-analysis was conducted to assess the benefits and risks of aspirin for the primary prevention of cardiovascular disease and all-cause mortality events in adults with diabetes. Methods: An extensive and systematic search was conducted in MEDLINE (via PubMed), Cinahl (via Ebsco), Scopus, and Web of Sciences from 1988 to December 2020. A detailed literature search was conducted using aspirin, cardiovascular disease (CVD), diabetes, and efficacy to identify trials of patients with...
Source
#1Victor Aboyans (University of Limoges)H-Index: 80
#2Rupert Bauersachs (University of Mainz)H-Index: 34
Last. Basil S. Lewis (Technion – Israel Institute of Technology)H-Index: 106
view all 16 authors...
The aim of this collaborative document is to provide an update for clinicians on best antithrombotic strategies in patients with aortic and/or peripheral arterial diseases. Antithrombotic therapy is a pillar of optimal medical treatment for these patients at very high cardiovascular risk. While the number of trials on antithrombotic therapies in patients with aortic or peripheral arterial diseases is substantially smaller than for those with coronary artery disease, recent evidence deserves to b...
1 CitationsSource
#1E.S. DebusH-Index: 10
Last. Rupert BauersachsH-Index: 34
view all 5 authors...
Source
#1Ahmed Ismaeel (Baylor University)H-Index: 6
#2K. Leigh Greathouse (Baylor University)H-Index: 8
Last. Robert J Widmer (Scott & White Hospital)H-Index: 8
view all 12 authors...
Peripheral artery disease (PAD) affects over 200 million people worldwide, resulting in significant morbidity and mortality, yet treatment options remain limited. Among the manifestations of PAD is a severe functional disability and decline, which is thought to be the result of different pathophysiological mechanisms including oxidative stress, skeletal muscle pathology, and reduced nitric oxide bioavailability. Thus, compounds that target these mechanisms may have a therapeutic effect on walkin...
Source
#2Erik Lerkevang Grove (AU: Aarhus University)H-Index: 32
Last. Anne-Mette Hvas (AU: Aarhus University)H-Index: 40
view all 3 authors...
The ability of aspirin to inhibit platelet aggregation has positioned this agent within the most frequently used drugs worldwide. The aim of this article is to review the contemporary clinical use of aspirin and also to discuss unresolved issues not yet translated into clinical practice. Results from several clinical trials have led to strong guideline recommendations for aspirin use in the acute management and secondary prevention of cardiovascular disease. On the contrary, guidelines regarding...
1 CitationsSource