Diabetes Mellitus
Conditions
Keywords
Diabetes Mellitus, Cardiovascular Disease, Aspirin, Omega-3 fatty acids, Primary prevention, Randomized Controlled Trial, Type 1 Diabetes Mellitus, Type 2 Diabetes Mellitus, n-3 fatty acid
Brief summary
The purpose of this study is to determine whether 100mg daily aspirin versus placebo and/or supplementation with 1 gram daily omega-3 fatty acids or placebo prevents serious vascular events (i.e. non-fatal heart attack, non-fatal stroke or transient ischaemic attack, or death from vascular causes) in patients with diabetes who are not known to have occlusive arterial disease and to assess the effects on serious bleeding or other adverse events.
Detailed description
The role of antiplatelet therapy (chiefly aspirin) for the secondary prevention of heart attacks and strokes is firmly established for many high-risk people with diagnosed arterial disease, and the proportional reductions in these cardiovascular events appear to be about one quarter, whether or not such patients have diabetes. But, most younger and middle-aged people with diabetes do not have manifest arterial disease - although they are still at significant cardiovascular risk - and yet few trials have tested aspirin in such individuals. As a result, there is substantial uncertainty about the role of aspirin for the prevention of heart attacks and strokes among apparently healthy people with diabetes, and only a small minority receives it. There is consistent evidence from observational studies of lower rates of cardiovascular disease (particularly cardiac and sudden death) in people with higher intakes, or higher blood levels, of fish oils (omega-3 fatty acids). Trials in people who have survived a heart attack have shown modest, but potentially worthwhile, reductions in coronary events. If ASCEND can reliably demonstrate that aspirin and/or fish oils safely reduce the risk of cardiovascular events and deaths in people with diabetes who do not have pre-existing arterial disease, then this would be relevant to some tens of millions of people world-wide (who are currently not receiving such therapy) and might save tens of thousands of lives each year. The initial results (published 2018) showed that aspirin prevented serious vascular events in patients with diabetes who did not already have cardiovascular disease, but it caused almost as many major bleeds and there was no effect on cancers. There was no significant difference in the risk of serious vascular events between those who were assigned to receive n-3 fatty acid supplementation and those who were assigned to receive placebo. ASCEND will be conducting long-term follow-up for 20-years beyond the scheduled treatment period (which ended in 2017). We will collect relevant data from UK central health registries. This will be used to assess whether the balance of benefits versus hazards of aspirin observed within the main trial, relating to major vascular events such as heart attack or stroke, continue long-term or whether additional benefits emerge during longer-term follow-up. In addition ASCEND will use this long-term post-trial follow-up to investigate further whether low-dose aspirin might protect against cancer. The main cancer analyses is planned to take place \ 5-years after the end of the treatment period.
Interventions
Sponsors
British Heart Foundation
Bayer
Medical Research Council
Solvay Pharmaceuticals
Abbott
Mylan
Health Data Research UK
Alzheimer's Research UK
The Macular Society
University of Oxford
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Males or females with type 1 or type 2 diabetes mellitus. * Aged ≥ 40 years. * No previous history of vascular disease. * No clear contra-indication to aspirin. * No other predominant life-threatening medical problem.
Exclusion criteria
* Definite history of myocardial infarction, stroke or arterial revascularisation procedure. * Currently prescribed aspirin, warfarin or any other blood thinning medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With First Occurrence of Any Serious Vascular Event (SVE) | Randomized treatment phase during a mean of 7.4 years | The primary efficacy assessments involve intention-to-treat comparisons among all randomized participants of allocation to aspirin versus placebo and, separately, of omega-3 fatty acids versus placebo on the first occurrence of any Serious Vascular Event (SVE), defined as: * non-fatal myocardial infarction; or * non-fatal stroke (excluding confirmed intracranial hemorrhage) or TIA; or * vascular death excluding confirmed intracranial hemorrhage (defined as International Classification of Diseases 10th revision \[ICD-10\] I00-52 or I63-99, i.e. excluding subarachnoid hemorrhage \[I60\], intracerebral hemorrhage \[I61\], and other non-traumatic intracranial hemorrhage \[I62\]). |
| Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only) | Randomized treatment phase during a mean of 7.4 years | The primary safety assessments involve intention-to-treat comparisons among all randomized patients of allocation to aspirin versus placebo on the first occurrence of any major bleed, defined as: * any confirmed intracranial hemorrhage (including intracerebral, subarachnoid, subdural or any other intracranial hemorrhage); or * sight-threatening eye bleeding; or * any other serious bleeding episode. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only) | Randomized treatment phase during a mean of 7.4 years | Secondary efficacy assessments of aspirin involve intention-to-treat comparisons during the scheduled treatment period among all randomized participants on the first occurrence of: Any incident gastrointestinal (GI) tract cancer (i.e. any GI cancer excluding pancreas and hepatobiliary), overall and after exclusion of the first three years of follow-up. |
| Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations | Randomized treatment phase during a mean of 7.4 years | Secondary efficacy assessments involve intention-to-treat comparisons among all randomized participants of allocation to aspirin versus placebo and, separately, of omega-3 versus placebo on the first occurrence of the expanded vascular endpoint of SVE or revascularization (including coronary and non-coronary revascularizations). |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Fatal Event: All Stroke | Randomized treatment phase during a mean of 7.4 years | Fatal 'All stroke' events include deaths from: Haemorrhagic stroke (Intracerebral haemorrhage; Subarachnoid haemorrhage); Non-haemorrhagic stroke (Cerebral infarction; Stroke not specified as haemorrhage or infarction). |
| Number of Participants With Fatal Event: Other Vascular | Randomized treatment phase during a mean of 7.4 years | Fatal 'Other vascular' events include deaths from: Heart failure (excluding ischaemic cardiomyopathy); Other vascular death (excluding stroke; and Cardiac death (excluding CHD). |
| Number of Participants With Fatal Event: Cancer | Randomized treatment phase during a mean of 7.4 years | Fatal 'Cancer' events include any death attributed to cancer. |
| Number of Participants With Fatal Event: Respiratory | Randomized treatment phase during a mean of 7.4 years | Fatal 'Respiratory' events include any death attributed to respiratory causes. |
| Number of Participants With Fatal Event: Other Medical | Randomized treatment phase during a mean of 7.4 years | Fatal 'Other medical' events include deaths from: Non-vascular medical causes (excluding cancer and respiratory, including Fatal GI bleed or perforation); and deaths from Renal disease and Diabetes. |
| Number of Participants With Fatal Event: External Cause | Randomized treatment phase during a mean of 7.4 years | Fatal 'External cause' events include deaths from: Injury; Fracture; Self harm; and Medical and surgical complications |
| Number of Participants With Fatal Event: Unknown Cause | Randomized treatment phase during a mean of 7.4 years | Any death for which the cause is not known. |
| Number of Participants With Event: Any Cancer | Randomized treatment phase during a mean of 7.4 years | Incidence of fatal or non-fatal cancers. Any cancer excludes non-fatal non-melanoma skin cancer and non-fatal recurrence of a cancer that had occurred before randomization. A single participant may have had multiple cancers. |
| Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only) | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal cancers. Excludes cancers reported in the gastrointestinal tract category (see secondary outcome measure #4), and includes hepatobiliary and pancreatic cancers. |
| Number of Participants With Event: Respiratory Cancer | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal cancers. Includes lung and larynx cancer. |
| Number of Participants With Event: Genitourinary Cancer | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal renal, bladder, prostate, gynaecological and other GU cancers |
| Number of Participants With Event: Hematological Cancer | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal cancers. Includes leukaemia and lymphoma. |
| Number of Participants With Event: Breast Cancer | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal cancers. |
| Number of Participants With Event: Melanoma | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal melanomas. |
| Number of Participants With Event: Other Cancer | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal cancers not included elsewhere (where the type of cancer is known). |
| Number of Participants With Event: Unspecified Cancer | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal cancers of unknown type. |
| Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only) | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal events. |
| Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only) | Randomized treatment phase during a mean of 7.4 years | Includes fatal and non-fatal events, excludes atrial fibrillation. |
| Number of Participants With Fatal Event: All-cause Mortality | Randomized treatment phase during a mean of 7.4 years | 'All-cause mortality' includes all recorded deaths. |
| Number of Participants With Fatal Event: Coronary | Randomized treatment phase during a mean of 7.4 years | Fatal 'Coronary' events include deaths from: Acute MI and other CHD (unspecified Acute ischaemic heart disease; Atherosclerotic heart disease; Ischaemic cardiomyopathy; unspecified Chronic ischaemic heart disease). |
Countries
United Kingdom
Participant flow
Recruitment details
Participants were randomized between June 2005 through July 2011. Follow-up continued until March 2018.
Participants by arm
| Arm | Count |
|---|---|
| Aspirin + Omega-3 Participants receive 100mg of aspirin once daily and 1g of omega-3 ethyl esters once daily. | 3,870 |
| Aspirin + Placebo Omega-3 Participants receive 100mg of aspirin once daily and placebo omega-3 ethyl esters once daily. | 3,870 |
| Placebo Aspirin + Omega-3 Participants receive placebo aspirin once daily and 1g of omega-3 ethyl esters once daily. | 3,870 |
| Placebo Aspirin + Placebo Omega-3 Participants receive placebo aspirin once daily and placebo omega-3 ethyl esters once daily. | 3,870 |
| Total | 15,480 |
Baseline characteristics
| Characteristic | Aspirin + Placebo Omega-3 | Total | Aspirin + Omega-3 | Placebo Aspirin + Placebo Omega-3 | Placebo Aspirin + Omega-3 |
|---|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1611 Participants | 6446 Participants | 1613 Participants | 1609 Participants | 1613 Participants |
| Age, Categorical Between 18 and 65 years | 2259 Participants | 9034 Participants | 2257 Participants | 2261 Participants | 2257 Participants |
| Age, Continuous | 63.2 years STANDARD_DEVIATION 9.1 | 63.3 years STANDARD_DEVIATION 9.2 | 63.2 years STANDARD_DEVIATION 9.3 | 63.3 years STANDARD_DEVIATION 9.2 | 63.3 years STANDARD_DEVIATION 9.2 |
| Aspirin use prior to screening No | 2503 Participants | 9972 Participants | 2497 Participants | 2473 Participants | 2499 Participants |
| Aspirin use prior to screening Yes | 1367 Participants | 5508 Participants | 1373 Participants | 1397 Participants | 1371 Participants |
| Body-mass index (kg/m²) <25 | 558 Participants | 2249 Participants | 522 Participants | 562 Participants | 607 Participants |
| Body-mass index (kg/m²) ≥25 to <30 | 1397 Participants | 5529 Participants | 1356 Participants | 1361 Participants | 1415 Participants |
| Body-mass index (kg/m²) ≥30 | 1802 Participants | 7201 Participants | 1863 Participants | 1815 Participants | 1721 Participants |
| Body-mass index (kg/m²) Unknown | 113 Participants | 501 Participants | 129 Participants | 132 Participants | 127 Participants |
| Body-mass index (mean) | 30.8 kg/m² STANDARD_DEVIATION 6.2 | 30.7 kg/m² STANDARD_DEVIATION 6.3 | 30.9 kg/m² STANDARD_DEVIATION 6.3 | 30.7 kg/m² STANDARD_DEVIATION 6.3 | 30.5 kg/m² STANDARD_DEVIATION 6.3 |
| Duration of diabetes (years) ≥13 yr | 213 Participants | 856 Participants | 214 Participants | 215 Participants | 214 Participants |
| Duration of diabetes (years) ≥6 <13 yr | 1492 Participants | 5965 Participants | 1484 Participants | 1493 Participants | 1496 Participants |
| Duration of diabetes (years) <6 yr | 2165 Participants | 8659 Participants | 2172 Participants | 2162 Participants | 2160 Participants |
| Duration of diabetes (years) | 7 years | 7 years | 7 years | 7 years | 7 years |
| Race/Ethnicity, Customized Ethnic origin African/Caribbean | 36 Participants | 140 Participants | 34 Participants | 34 Participants | 36 Participants |
| Race/Ethnicity, Customized Ethnic origin Indian/Pakistani/Bangladeshi | 45 Participants | 184 Participants | 46 Participants | 47 Participants | 46 Participants |
| Race/Ethnicity, Customized Ethnic origin Other/unknown | 55 Participants | 221 Participants | 57 Participants | 55 Participants | 54 Participants |
| Race/Ethnicity, Customized Ethnic origin White | 3734 Participants | 14935 Participants | 3733 Participants | 3734 Participants | 3734 Participants |
| Region of Enrollment United Kingdom | 3870 participants | 15480 participants | 3870 participants | 3870 participants | 3870 participants |
| Sex: Female, Male Female | 1449 Participants | 5796 Participants | 1448 Participants | 1449 Participants | 1450 Participants |
| Sex: Female, Male Male | 2421 Participants | 9684 Participants | 2422 Participants | 2421 Participants | 2420 Participants |
| Smoking status Current smoker | 320 Participants | 1279 Participants | 319 Participants | 320 Participants | 320 Participants |
| Smoking status Ex-smoker | 1762 Participants | 7051 Participants | 1764 Participants | 1762 Participants | 1763 Participants |
| Smoking status Never smoked | 1744 Participants | 6977 Participants | 1745 Participants | 1744 Participants | 1744 Participants |
| Smoking status Unknown | 44 Participants | 173 Participants | 42 Participants | 44 Participants | 43 Participants |
| Systolic blood pressure (mean) | 136.1 mmHg STANDARD_DEVIATION 15 | 136.2 mmHg STANDARD_DEVIATION 15.3 | 136.1 mmHg STANDARD_DEVIATION 15.4 | 136.2 mmHg STANDARD_DEVIATION 15.2 | 136.2 mmHg STANDARD_DEVIATION 15.3 |
| Systolic blood pressure (mmHg) <130 mmHg | 845 Participants | 3394 Participants | 849 Participants | 854 Participants | 846 Participants |
| Systolic blood pressure (mmHg) ≥130 to <140 mmHg | 786 Participants | 3091 Participants | 764 Participants | 758 Participants | 783 Participants |
| Systolic blood pressure (mmHg) ≥140 mmHg | 1123 Participants | 4555 Participants | 1140 Participants | 1153 Participants | 1139 Participants |
| Systolic blood pressure (mmHg) Unknown | 1116 Participants | 4440 Participants | 1117 Participants | 1105 Participants | 1102 Participants |
| Treated hypertension No | 1460 Participants | 5835 Participants | 1459 Participants | 1458 Participants | 1458 Participants |
| Treated hypertension Unknown | 28 Participants | 112 Participants | 27 Participants | 29 Participants | 28 Participants |
| Treated hypertension Yes | 2382 Participants | 9533 Participants | 2384 Participants | 2383 Participants | 2384 Participants |
| Type of diabetes Type 1 | 232 Participants | 911 Participants | 226 Participants | 219 Participants | 234 Participants |
| Type of diabetes Type 2 | 3638 Participants | 14569 Participants | 3644 Participants | 3651 Participants | 3636 Participants |
| Vascular risk score High (≥10%) | 650 Participants | 2668 Participants | 668 Participants | 691 Participants | 659 Participants |
| Vascular risk score Low (<5%) | 1561 Participants | 6264 Participants | 1567 Participants | 1559 Participants | 1577 Participants |
| Vascular risk score Moderate (≥5%, <10%) | 1659 Participants | 6548 Participants | 1635 Participants | 1620 Participants | 1634 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 748 / 7,740 | 792 / 7,740 | 752 / 7,740 | 788 / 7,740 |
| other Total, other adverse events | 0 / 0 | 0 / 0 | 0 / 0 | 0 / 0 |
| serious Total, serious adverse events | 5,264 / 7,740 | 5,321 / 7,740 | 5,344 / 7,740 | 5,241 / 7,740 |
Outcome results
Primary
Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only)
The primary safety assessments involve intention-to-treat comparisons among all randomized patients of allocation to aspirin versus placebo on the first occurrence of any major bleed, defined as: * any confirmed intracranial hemorrhage (including intracerebral, subarachnoid, subdural or any other intracranial hemorrhage); or * sight-threatening eye bleeding; or * any other serious bleeding episode.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only) | 314 Participants |
| Placebo Aspirin | Number of Participants With First Occurrence of Any Major Bleed (Aspirin Comparison Only) | 245 Participants |
p-value: 0.00395% CI: [1.09, 1.52]Log Rank
Primary
Number of Participants With First Occurrence of Any Serious Vascular Event (SVE)
The primary efficacy assessments involve intention-to-treat comparisons among all randomized participants of allocation to aspirin versus placebo and, separately, of omega-3 fatty acids versus placebo on the first occurrence of any Serious Vascular Event (SVE), defined as: * non-fatal myocardial infarction; or * non-fatal stroke (excluding confirmed intracranial hemorrhage) or TIA; or * vascular death excluding confirmed intracranial hemorrhage (defined as International Classification of Diseases 10th revision \[ICD-10\] I00-52 or I63-99, i.e. excluding subarachnoid hemorrhage \[I60\], intracerebral hemorrhage \[I61\], and other non-traumatic intracranial hemorrhage \[I62\]).
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With First Occurrence of Any Serious Vascular Event (SVE) | 658 Participants |
| Placebo Aspirin | Number of Participants With First Occurrence of Any Serious Vascular Event (SVE) | 743 Participants |
| Omega-3 | Number of Participants With First Occurrence of Any Serious Vascular Event (SVE) | 689 Participants |
| Placebo Omega-3 | Number of Participants With First Occurrence of Any Serious Vascular Event (SVE) | 712 Participants |
p-value: 0.0195% CI: [0.79, 0.97]Log Rank
p-value: 0.5595% CI: [0.87, 1.08]Log Rank
Secondary
Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only)
Secondary efficacy assessments of aspirin involve intention-to-treat comparisons during the scheduled treatment period among all randomized participants on the first occurrence of: Any incident gastrointestinal (GI) tract cancer (i.e. any GI cancer excluding pancreas and hepatobiliary), overall and after exclusion of the first three years of follow-up.
Time frame: Randomized treatment phase during a mean of 7.4 years
Population: Participants taking aspirin
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only) | 157 Participants |
| Placebo Aspirin | Number of Participants With Any Incident Gastrointestinal (GI) Tract Cancer (Aspirin Comparison Only) | 158 Participants |
95% CI: [0.8, 1.24]
Secondary
Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations
Secondary efficacy assessments involve intention-to-treat comparisons among all randomized participants of allocation to aspirin versus placebo and, separately, of omega-3 versus placebo on the first occurrence of the expanded vascular endpoint of SVE or revascularization (including coronary and non-coronary revascularizations).
Time frame: Randomized treatment phase during a mean of 7.4 years
Population: A single participant may have had multiple events.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations | 833 Participants |
| Placebo Aspirin | Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations | 936 Participants |
| Omega-3 | Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations | 882 Participants |
| Placebo Omega-3 | Number of Participants With Combined End-point of Serious Vascular Events (SVEs) or Revascularizations | 887 Participants |
95% CI: [0.8, 0.97]
95% CI: [0.91, 1.09]
Other Pre-specified
Number of Participants With Event: Any Cancer
Incidence of fatal or non-fatal cancers. Any cancer excludes non-fatal non-melanoma skin cancer and non-fatal recurrence of a cancer that had occurred before randomization. A single participant may have had multiple cancers.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Any Cancer | 897 Participants |
| Placebo Aspirin | Number of Participants With Event: Any Cancer | 887 Participants |
| Omega-3 | Number of Participants With Event: Any Cancer | 894 Participants |
| Placebo Omega-3 | Number of Participants With Event: Any Cancer | 890 Participants |
95% CI: [0.92, 1.11]
95% CI: [0.91, 1.1]
Other Pre-specified
Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only)
Includes fatal and non-fatal events.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only) | 166 Participants |
| Placebo Aspirin | Number of Participants With Event: Atrial Fibrillation (Omega-3 Comparison Only) | 135 Participants |
95% CI: [0.98, 1.54]
Other Pre-specified
Number of Participants With Event: Breast Cancer
Includes fatal and non-fatal cancers.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Breast Cancer | 97 Participants |
| Placebo Aspirin | Number of Participants With Event: Breast Cancer | 96 Participants |
| Omega-3 | Number of Participants With Event: Breast Cancer | 103 Participants |
| Placebo Omega-3 | Number of Participants With Event: Breast Cancer | 90 Participants |
95% CI: [0.76, 1.34]
95% CI: [0.86, 1.52]
Other Pre-specified
Number of Participants With Event: Genitourinary Cancer
Includes fatal and non-fatal renal, bladder, prostate, gynaecological and other GU cancers
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Genitourinary Cancer | 332 Participants |
| Placebo Aspirin | Number of Participants With Event: Genitourinary Cancer | 294 Participants |
| Omega-3 | Number of Participants With Event: Genitourinary Cancer | 323 Participants |
| Placebo Omega-3 | Number of Participants With Event: Genitourinary Cancer | 303 Participants |
95% CI: [0.97, 1.32]
95% CI: [0.91, 1.25]
Other Pre-specified
Number of Participants With Event: Hematological Cancer
Includes fatal and non-fatal cancers. Includes leukaemia and lymphoma.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Hematological Cancer | 88 Participants |
| Placebo Aspirin | Number of Participants With Event: Hematological Cancer | 86 Participants |
| Omega-3 | Number of Participants With Event: Hematological Cancer | 94 Participants |
| Placebo Omega-3 | Number of Participants With Event: Hematological Cancer | 80 Participants |
95% CI: [0.76, 1.38]
95% CI: [0.87, 1.58]
Other Pre-specified
Number of Participants With Event: Melanoma
Includes fatal and non-fatal melanomas.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Melanoma | 50 Participants |
| Placebo Aspirin | Number of Participants With Event: Melanoma | 59 Participants |
| Omega-3 | Number of Participants With Event: Melanoma | 55 Participants |
| Placebo Omega-3 | Number of Participants With Event: Melanoma | 54 Participants |
95% CI: [0.58, 1.23]
95% CI: [0.7, 1.48]
Other Pre-specified
Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only)
Includes fatal and non-fatal events, excludes atrial fibrillation.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only) | 83 Participants |
| Placebo Aspirin | Number of Participants With Event: Other Arrhythmia (Omega-3 Comparison Only) | 99 Participants |
95% CI: [0.63, 1.12]
Other Pre-specified
Number of Participants With Event: Other Cancer
Includes fatal and non-fatal cancers not included elsewhere (where the type of cancer is known).
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Other Cancer | 25 Participants |
| Placebo Aspirin | Number of Participants With Event: Other Cancer | 30 Participants |
| Omega-3 | Number of Participants With Event: Other Cancer | 23 Participants |
| Placebo Omega-3 | Number of Participants With Event: Other Cancer | 32 Participants |
95% CI: [0.49, 1.41]
95% CI: [0.42, 1.22]
Other Pre-specified
Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only)
Includes fatal and non-fatal cancers. Excludes cancers reported in the gastrointestinal tract category (see secondary outcome measure #4), and includes hepatobiliary and pancreatic cancers.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only) | 87 Participants |
| Placebo Aspirin | Number of Participants With Event: Other Gastrointestinal Cancer (Aspirin Comparison Only) | 82 Participants |
95% CI: [0.78, 1.43]
Other Pre-specified
Number of Participants With Event: Respiratory Cancer
Includes fatal and non-fatal cancers. Includes lung and larynx cancer.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Respiratory Cancer | 101 Participants |
| Placebo Aspirin | Number of Participants With Event: Respiratory Cancer | 103 Participants |
| Omega-3 | Number of Participants With Event: Respiratory Cancer | 104 Participants |
| Placebo Omega-3 | Number of Participants With Event: Respiratory Cancer | 100 Participants |
95% CI: [0.74, 1.29]
95% CI: [0.79, 1.37]
Other Pre-specified
Number of Participants With Event: Unspecified Cancer
Includes fatal and non-fatal cancers of unknown type.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Event: Unspecified Cancer | 26 Participants |
| Placebo Aspirin | Number of Participants With Event: Unspecified Cancer | 31 Participants |
| Omega-3 | Number of Participants With Event: Unspecified Cancer | 25 Participants |
| Placebo Omega-3 | Number of Participants With Event: Unspecified Cancer | 32 Participants |
95% CI: [0.5, 1.41]
95% CI: [0.46, 1.31]
Other Pre-specified
Number of Participants With Fatal Event: All-cause Mortality
'All-cause mortality' includes all recorded deaths.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: All-cause Mortality | 748 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: All-cause Mortality | 792 Participants |
| Omega-3 | Number of Participants With Fatal Event: All-cause Mortality | 752 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: All-cause Mortality | 788 Participants |
95% CI: [0.85, 1.04]
95% CI: [0.86, 1.05]
Other Pre-specified
Number of Participants With Fatal Event: All Stroke
Fatal 'All stroke' events include deaths from: Haemorrhagic stroke (Intracerebral haemorrhage; Subarachnoid haemorrhage); Non-haemorrhagic stroke (Cerebral infarction; Stroke not specified as haemorrhage or infarction).
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: All Stroke | 38 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: All Stroke | 34 Participants |
| Omega-3 | Number of Participants With Fatal Event: All Stroke | 35 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: All Stroke | 37 Participants |
95% CI: [0.7, 1.77]
95% CI: [0.59, 1.5]
Other Pre-specified
Number of Participants With Fatal Event: Cancer
Fatal 'Cancer' events include any death attributed to cancer.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: Cancer | 309 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: Cancer | 315 Participants |
| Omega-3 | Number of Participants With Fatal Event: Cancer | 305 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: Cancer | 319 Participants |
95% CI: [0.84, 1.15]
95% CI: [0.82, 1.12]
Other Pre-specified
Number of Participants With Fatal Event: Coronary
Fatal 'Coronary' events include deaths from: Acute MI and other CHD (unspecified Acute ischaemic heart disease; Atherosclerotic heart disease; Ischaemic cardiomyopathy; unspecified Chronic ischaemic heart disease).
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: Coronary | 105 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: Coronary | 122 Participants |
| Omega-3 | Number of Participants With Fatal Event: Coronary | 100 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: Coronary | 127 Participants |
95% CI: [0.66, 1.12]
95% CI: [0.61, 1.02]
Other Pre-specified
Number of Participants With Fatal Event: External Cause
Fatal 'External cause' events include deaths from: Injury; Fracture; Self harm; and Medical and surgical complications
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: External Cause | 18 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: External Cause | 21 Participants |
| Omega-3 | Number of Participants With Fatal Event: External Cause | 17 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: External Cause | 22 Participants |
95% CI: [0.41, 1.45]
95% CI: [0.46, 1.6]
Other Pre-specified
Number of Participants With Fatal Event: Other Medical
Fatal 'Other medical' events include deaths from: Non-vascular medical causes (excluding cancer and respiratory, including Fatal GI bleed or perforation); and deaths from Renal disease and Diabetes.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: Other Medical | 126 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: Other Medical | 157 Participants |
| Omega-3 | Number of Participants With Fatal Event: Other Medical | 158 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: Other Medical | 125 Participants |
95% CI: [0.64, 1.01]
95% CI: [1, 1.59]
Other Pre-specified
Number of Participants With Fatal Event: Other Vascular
Fatal 'Other vascular' events include deaths from: Heart failure (excluding ischaemic cardiomyopathy); Other vascular death (excluding stroke; and Cardiac death (excluding CHD).
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: Other Vascular | 67 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: Other Vascular | 70 Participants |
| Omega-3 | Number of Participants With Fatal Event: Other Vascular | 61 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: Other Vascular | 76 Participants |
95% CI: [0.68, 1.34]
95% CI: [0.57, 1.12]
Other Pre-specified
Number of Participants With Fatal Event: Respiratory
Fatal 'Respiratory' events include any death attributed to respiratory causes.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: Respiratory | 82 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: Respiratory | 69 Participants |
| Omega-3 | Number of Participants With Fatal Event: Respiratory | 73 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: Respiratory | 78 Participants |
95% CI: [0.86, 1.63]
95% CI: [0.68, 1.28]
Other Pre-specified
Number of Participants With Fatal Event: Unknown Cause
Any death for which the cause is not known.
Time frame: Randomized treatment phase during a mean of 7.4 years
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Aspirin | Number of Participants With Fatal Event: Unknown Cause | 3 Participants |
| Placebo Aspirin | Number of Participants With Fatal Event: Unknown Cause | 4 Participants |
| Omega-3 | Number of Participants With Fatal Event: Unknown Cause | 3 Participants |
| Placebo Omega-3 | Number of Participants With Fatal Event: Unknown Cause | 4 Participants |
95% CI: [0.17, 3.3]
95% CI: [0.17, 3.31]