What are recommendations for aspirin use for primary ASCVD prophylaxis?

Comment by InpharmD Researcher

Based on the most recent guidelines, routine aspirin is not universally recommended for primary atherosclerotic cardiovascular disease (ASCVD) prevention based on its modest cardiovascular benefit, which is offset by increased risk of bleeding. Instead, the guidance incorporates nuance into applicable recommendations. The U.S. Preventive Services Task Force supports individualized initiation at ages 40-59 years with ≥10% 10-year cardiovascular risk (Grade C) and recommends against initiation at ≥60 years (Grade D). The American College of Cardiology permits consideration in selected adults aged 40-70 years with higher cardiovascular risk and low bleeding risk. Finally, the American Diabetes Association permits aspirin 75-162 mg/day in selected adults with diabetes and increased cardiovascular risk after discussing benefits and bleeding risk (Grade A), generally discouraging use after age 70.
Background

The most recent 2026 American College of Cardiology scientific statement recommends that low-dose aspirin may be considered for primary ASCVD prevention in selected adults aged 40-70 years who have higher cardiovascular risk without increased bleeding risk. Routine use in adults older than 70 years should be avoided, and aspirin is associated with net harm in patients with high bleeding risk regardless of ASCVD risk or coronary artery calcium (CAC) score. Cardiovascular risk calculators, including the Pooled Cohort Equations and PREVENT equations, may help identify potential candidates. Of note, these are consensus recommendations without a specific level of evidence attributed to them. [1]

Supporting evidence cited in the statement includes a meta-analysis of 13 trials involving 165,265 participants in which aspirin modestly reduced cardiovascular events (HR 0.89) but increased major bleeding (HR 1.43), including gastrointestinal bleeding (HR 1.56) and intracranial bleeding (HR 1.34), without reducing all-cause mortality. Another meta-analysis found a smaller, nonsignificant reduction in myocardial infarction in trials initiated after 2000 compared with earlier trials; the authors suggest that greater use of contemporary preventive therapies, including statins, may explain the smaller incremental benefit. Analyses from observational cohorts suggest that CAC scores ≥100, particularly ≥400, may identify patients with a more favorable benefit-risk balance, while possible aspirin benefits associated with lipoprotein(a) appear limited to older carriers of specific genotypes. However, randomized trials selecting patients on the basis of elevated CAC or lipoprotein(a) are lacking, and the statement provides no separately graded recommendation for using these markers to initiate aspirin. [1]

Additionally, the 2026 American Diabetes Association Standards of Care recommend that aspirin 75-162 mg/day may be considered for primary ASCVD prevention in adults with diabetes who have increased cardiovascular risk, following a comprehensive discussion of cardiovascular benefits versus the comparable increase in bleeding risk (evidence grade A). Potential candidates include adults aged ≥50 years with diabetes and at least one additional major risk factor, such as hypertension, dyslipidemia, smoking, obesity, or chronic kidney disease, provided bleeding risk is not increased. Older age, anemia, and kidney disease are identified as bleeding-risk considerations. In adults >70 years, the balance generally favors harm, so primary-prevention aspirin is generally discouraged. Aspirin is also not recommended for adults <50 years with diabetes and no additional major ASCVD risk factors; intermediate-risk patients require clinical judgment. [2]

Supporting evidence includes an individual-participant meta-analysis of six primary-prevention trials involving over 95,000 participants, including almost 4,000 with diabetes, which found a 12% reduction in serious vascular events (RR 0.88, 95% CI 0.82-0.94), primarily through fewer nonfatal myocardial infarctions. In ASCEND, 15,480 adults with diabetes but no evident cardiovascular disease received aspirin 100 mg/day or placebo for a mean 7.4 years. Aspirin reduced serious vascular events (8.5% vs 9.6%; p= 0.01), but increased major bleeding (4.1% vs 3.2%; rate ratio 1.29; p= 0.003), predominantly gastrointestinal and other extracranial bleeding. ARRIVE and ASPREE further demonstrated no significant cardiovascular benefit in their respective populations, while gastrointestinal bleeding increased in ARRIVE and major hemorrhage increased in ASPREE (see tables). [2]

The 2022 U.S. Preventive Services Task Force recommendation statement advises that initiating low-dose aspirin for primary cardiovascular disease prevention should be an individual decision in adults aged 40-59 years with an estimated ≥10% 10-year cardiovascular risk (Grade C). The net benefit is small, with greater potential benefit in patients at higher cardiovascular risk who are not at increased bleeding risk. Initiation is not recommended in adults aged ≥60 years because there is no net benefit (Grade D). Both conclusions are supported by moderate certainty. These recommendations apply to adults without known cardiovascular disease or cardiovascular signs or symptoms. If aspirin is selected, 81 mg/day is a reasonable dose. Microsimulation modeling estimated modest net benefit from initiation at ages 40-59 years with ≥10% 10-year cardiovascular risk, generally negative life-years gained from initiation at ages 60-69, and losses in both life-years and quality-adjusted life-years from initiation at ages 70-79 across all modeled risk levels. For patients already taking aspirin, continuation should be reassessed according to age, cardiovascular risk, bleeding risk, and preferences. [3]

Background References: [1] Kumbhani DJ, Gibson CM, Kinlay S, et al. Antiplatelet Therapy in the Management of Atherosclerotic Cardiovascular Disease: 2026 ACC Scientific Statement: A Report of the American College of Cardiology. J Am Coll Cardiol. 2026;88(11):1284-1313. doi:10.1016/j.jacc.2026.05.037
[2] American Diabetes Association Professional Practice Committee for Diabetes*. 10. Cardiovascular Disease and Risk Management: Standards of Care in Diabetes-2026. Diabetes Care. 2026;49(Suppl 1):S216-S245. doi:10.2337/dc26-S010
[3] US Preventive Services Task Force. Aspirin use to prevent cardiovascular disease: US Preventive Services Task Force recommendation statement. JAMA. 2022;327(16):1577-1584. doi:10.1001/jama.2022.4983. JAMA Network
Literature Review

A search of the published medical literature revealed 5 studies investigating the researchable question:

What are recommendations for aspirin use for primary ASCVD prophylaxis?

Level of evidence

B - One high-quality study or multiple studies with limitations  Read more→


Please see Tables 1-5 for your response.

 

Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus (ASCEND)

Design

Randomized, double-blind, placebo-controlled trial

N=15,480

Objective

To assess the efficacy and safety of enteric-coated aspirin at a dose of 100 mg daily, as compared with placebo, in persons who had diabetes without manifest cardiovascular disease

Study Groups

Aspirin (n=7,740)

Placebo (n=7,740)

Methods

Inclusion criteria: age ≥40 years, diagnosed with diabetes mellitus (any type), no known cardiovascular disease

Exclusion criteria: a clear indication for aspirin, contraindication to aspirin

After an 8-10 week run-in period to assess adherence, eligible participants were randomized 1:1 to aspirin 100 mg or placebo.

Duration

Follow-up: 7.4 years

Outcome Measures

 First serious vascular event (composite of nonfatal myocardial infarction, nonfatal stroke, transient ischemic attack (TIA), or death from any vascular cause), major bleeding

Baseline Characteristics

  

Aspirin (n=7,740)

Placebo (n=7,740)

  

Age, years

 63.2 ± 9.2 63.3 ± 9.2  

Male

 4,843 (62.6%) 4,841 (62.5%)  

Body mass index, kg/m2

 30.8 ± 6.2 30.6 ± 6.3  

Hypertension

 4,766 (61.6%) 4,767 (61.6%)  

Smoking status

Current smoker

Former smoker

 

639 (8.3%)

3,526 (45.6%)

 

640 (8.3%)

3,525 (45.5%)

  

Results

 

Aspirin (n=7,740)

Placebo (n=7,740)

p-value

Any vascular event*

Nonfatal myocardial infarction

Nonfatal stroke

Transient ischemic attack

658 (8.5%)

191 (2.5%)

202 (2.6%)

168 (2.2%)

743 (9.6%)

195 (2.5%)

229 (3.0%)

197 (2.5%)

0.01

 

 

 

Major bleeding

Intracranial hemorrhage

Serious gastrointestinal bleeding

314 (4.1%)

55 (0.7%)

137 (1.8%)

245 (3.2%)

45 (0.6%)

101 (1.3%)

0.003

 

 
*Vascular events not including transient ischemic attack were not statistically significant

Adverse Events

 N/A

Study Author Conclusions

 Aspirin use prevented serious vascular events in persons who had diabetes and no evident cardiovascular disease at trial entry, but it also caused major bleeding events. The absolute benefits were largely counterbalanced by the bleeding hazard.

InpharmD Researcher Critique

Diabetes was well-controlled in the majority of patients (mean A1c <8 in 80% of patients at enrollment) and the majority of patients were on a statin at baseline. Thus, results may not be generalizable to patients with more severe diabetes, who would be expected to have a higher risk for vascular events. Despite the fact that nearly half of the major bleeding events observed were gastrointestinal bleeds, only 25% of patients were prescribed proton pump inhibitors (PPI) by the end of the trial. Excess bleeding due to aspirin may have been mitigated by more routine PPI use.

 

Table 1 References:
[4] Bowman L, Mafham M, Wallendszus K, et al. Effects of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med. 2018;379(16):1529-1539.

 

Use of Aspirin to Reduce Risk of Initial Vascular Events in Patients at Moderate Risk of Cardiovascular Disease (ARRIVE): A Randomised, Double-Blind, Placebo-Controlled Trial

Design

Randomized, double-blind, placebo-controlled, multicentered 

N= 12,546

Objective

To investigate the efficacy of 100 mg enteric-coated aspirin daily versus placebo in the reduction of incident myocardial infarction, stroke, and related cardiovascular conditions in people at moderate risk (defined as 10-20% 10-year coronary heart disease, with the exclusion of patients with diabetes)

Study Groups

Aspirin (n=6,270)

Placebo (n=6,276)

Methods

Inclusion criteria: males ≥55 years and had between two and four risk factors, females ≥60 years and had three or more risk factors (risk factors include: high cholesterol [total cholesterol >200mg/dL or LDL >130mg/dL for men; total cholesterol >240mg/dL or LDL > 160mg/dL for women], currently smoking or smoking in the past 12 months, low HDL cholesterol [<40 mg/dL], high blood pressure [systolic blood pressure >140 mm Hg], currently on medication to treat high blood pressure, or a family history of cardiovascular heart disease)

Exclusion criteria: diabetes, history of vascular event (e.g. stroke, myocardial infarction, coronary artery angioplasty or stenting, coronary artery bypass graft, congestive heart failure), relevant arrhythmias, participants that required antiplatelet therapy, or participants at a high risk of or history of gastrointestinal bleeding

Participants were randomized to either receive 100 mg enteric-coated aspirin or placebo tablets once daily at 501 sites in seven countries.

Duration

Follow-up: 5 years

Outcome Measures

First occurrence of myocardial infarction (MI), transient ischemic attack (TIA), cardiovascular death (CVD), stroke, or unstable angina; incidence of adverse events and bleeding

Baseline Characteristics

  

Aspirin (n=6,270)

Placebo (n=6,276)

  

Age, years

 63.9 ± 7.1 63.9 ± 7.1  
Male 4,419 (70.5%) 4,419 (70.4%)  
Smoker 1,808 (28.8%) 1,786 (28.5%)  
Taking antihypertensive medications 4038 (64.4%) 4097 (65.3%)  
Estimated 10-year ASCVD risk score, % 17.3 ± 9.8 17.4 ± 9.7  

Results

  

Aspirin (n=6,270)

Placebo (n=6,276)

P-value

Composite vascular event

Myocardial infarcation

Stroke

Cardiovascular death

269 (4.29%)

95 (1.52%)

75 (1.20%)

38 (0.61%)

281 (4.48%)

112 (1.78%)

67 (1.07%)

39 (0.62%)

0.6038

0.2325

0.5072

0.9010
Any death 160 (2.55%) 161 (2.57%) 0.9459

Gastrointestinal bleeding

Hemorrhagic stroke

61 (0.97%)

8 (0.13%)

29 (0.46%)

11 (0.18%)

 N/A

Adverse Events

Aspirin: gastrointestinal bleed (0.97%), osteoarthritis (1.66%), coronary artery disease (0.73%), acute myocardial infarction (0.69%)

Placebo: gastrointestinal bleed (0.46%), osteoarthritis (1.64%), coronary artery disease (0.97%), acute myocardial infarction (0.61%)

Study Author Conclusions

These results showed aspirin’s ability to lower the risk of first non-fatal myocardial infarction without affecting the risk of total stroke. With respect to safety, as expected, rates of gastrointestinal bleeding events and some other minor bleeding events were higher in the aspirin treatment group, but there was no significant difference in the incidence of fatal events.

InpharmD Researcher Critique

This was a large randomized controlled trial including patients with multiple risk factors for CV disease; however, the population excluded patients with diabetes, and the study was primarily done with patients at low risk. Due to a lower than anticipated event rate, originally planned for an event-driven design was modified to time-driven, the initial primary endpoints were expanded to include unstable angina and transient ischemic attack (TIA), and the observation period was expanded as well. 



Table 2 References:
[5] Gaziano JM, Brotons C, Coppolecchia R, et al. Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial. The Lancet. 2018;392(10152):1036-1046.

 

Effect of Aspirin on Disability-free Survival in the Healthy Elderly (ASPREE)

Design

Randomized, double-blinded, placebo-controlled trial

N=19,114

Objective

To investigate whether the daily use of aspirin, at a dose of 100 mg, in healthy, community-dwelling older adults would prolong healthy life span, free from dementia and persistent physical disability

Study Groups

Aspirin (n=9,525)

Placebo (n=9,589)

Methods

Inclusion criteria: community-dwelling men and women from Australia and the United States, aged ≥70 years or older (or≥65 years of age among blacks and Hispanics in the United States)

Exclusion criteria: diagnosed with dementia, known risk of bleeding, history of a diagnosed cardiovascular event, atrial fibrillation

Participants who met eligibility criteria were enrolled in a four-week placebo run-in phase to assess compliance. Those with an 80% or greater compliance were randomized 1:1 to receive either aspirin 100 mg or placebo daily. 

Duration

Median follow-up: 4.7 years (terminated early)

Outcome Measures

 Composite primary endpoint of all-cause mortality, dementia, or persistent physical disability; major hemorrhagic event

Baseline Characteristics

  

Aspirin (n=9,525)

Placebo (n=9,589)

  

Age, years

65-73

≥74

 

4,719 (49.5%)

4,806 (50.5%)

 

4,823 (50.3%)

4,766 (49.7%)

  

Female

 5,373 (56.4%) 5,410 (56.4%)  

White

 8,708 (91.4%) 8,742 (91.1%)  

BMI, kg/m2

 28.1 ± 4.8 28.1 ± 4.7  

Comorbidities

Diabetes

Hypertension

Dyslipidemia

Smoking

 

1,027 (10.8%)

7,065 (74.2%)

6,159 (64.7%)

352 (3.7%)

 

1,030 (10.7%)

7,148 (74.5%)

6,308 (65.8%)

383 (4.0%)

  

Results

  

Aspirin (n=9,525)

Placebo (n=9,589)

p-value

Composite primary endpoint (event rate per 1,000 person-years)

All-cause mortality

Dementia

Persistent physical disability

921 (21.5)

480 (11.2)

274 (6.4)

167 (3.9)

914 (21.2)

431 (10.0)

275 (6.4)

208 (4.8)

0.79

 

 

 

Major hemorrhagic event (event rate per 1,000 person-years)

Clinically significant bleeding

Hemorrhagic stroke

361 (8.6)

312 (7.4)

49 (1.2)

265 (6.2)

225 (5.3)

40 (0.9)

<0.001

 

 

Adverse Events

 N/A

Study Author Conclusions

Over a median follow-up of 4.7 years, the use of low-dose aspirin in persons 70 years of age or older who did not have cardiovascular disease did not prolong disability-free survival in a predominantly white population. This study was stopped early due to a lack of benefit seen with aspirin.

InpharmD Researcher Critique

Strengths of this study include the robust, randomized, placebo-controlled, double-blinded design in a large population. The study, while multicenter, was only conducted in the United States and Australia and in a predominantly white population (91%), which may limit its generalizability. 

 

Table 3 References:
[6] McNeil JJ, Woods RL, Nelson MR, et al. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med. 2018;379(16):1499-1508.

 

Subgroup analysis of the ASPirin in Reducing Events in the Elderly (ASPREE) randomized clinical trial suggest aspirin did not improve outcomes in older adults with chronic kidney disease

Design

A retrospective, cohort subgroup analysis of ASPREE trial

N=4,758

Objective

To examine the potential benefits and harms of aspirin in participants of ASPREE trial who had CKD compared to those patients without chronic kidney disease (CKD)

Study Groups

Aspirin (n=2,379)

Placebo (n=2,379)

Inclusion Criteria

Participants of ASPREE trial (patients without established CVD) who had CKD

Exclusion Criteria

Having stage 5 CKD, history of dialysis, history of kidney transplant or not having the estimated glomerular filtration rate (eGFR) or urine albumin:creatinine ratio (UACR) data at baseline

Methods

This is a post hoc secondary analysis of ASPREE. ASPREE trial was a large (N= 19,114) double-blind, randomized, placebo-controlled trial including community-dwelling adults aged 70 years and older in Australia, 65 years and older in the United States without a history of atherothrombotic cardiovascular disease and assessed whether daily treatment with enteric-coated aspirin (100 mg) decreased the risk of the composite endpoint of dementia, persistent physical disability, or death. Cardiovascular (CVD) events and bleeding were the secondary endpoints in ASPREE trial. CKD was defined as present at baseline if either eGFR under 60mL/min/1.73m2 or urine albumin to creatinine ratio 3 mg/mmol or more.

Duration

 ASPREE trial median follow-up: 4.7 years (terminated early)

Outcome Measures

Dementia, persistent physical disability, or death, major adverse cardiovascular events, bleeding, myocardial infarction, ischemic stroke, all-cause mortality, cardiovascular mortality

Baseline Characteristics

  

Aspirin

(n=2,379)

Placebo

(n=2,379)

Overall

(N=4,758)

        

Age, years

65-69

70-74

75-79

80-84

≥85

 

59 (2 %)

1,059 (45 %)

650 (27 %)

436 (18 %)

175 (7 %) 

 

62 (3 %)

1,025 (43 %)

662 (28 %)

451 (19 %)

179 (8 %) 

 

121 (3 %)

2,084 (44 %)

1,312 (28 %)

887 (19 %)

354 (7 %) 

 

 

      

Female

 1,345 (57 %)  1,355 (57 %) 2,700 (57 %)         

Race

White Australian

White USA

Africaan American

 

1,991 (84 %)

177 (7 %)

115 (5 %)

 

2,003 (84 %)

144 (6 %)

135 (6 %)

 

3,994 (84 %)

321 (7 %)

250 (5 %)

 

 

      

Current smoker

 82 (3 %) 113 (5 %) 195 (4 %)         

Current alcohol user

 1,730 (73 %) 1,731 (73 %) 3,461 (73 %)        

Comorbidities

Diabetes mellitus

Hypertension

Dyslipidemia

 

360 (15 %)

1,974 (83 %)

1,594 (67 %)

 

365 (15 %)

1,987 (84 %)

1,613 (68 %)

 

725 (15 %)

3,961 (83 %)

3,207 (67 %)

 

 

      

Previous regular aspirin use

285 (12 %)

288 (12 %)

 573 (12 %)

 

      

NSAID* use at baseline

334 (14 %)

329 (14 %)

 663 (14 %)

 

      

PPI# use at baseline

630 (26 %)

637 (27 %)

 1,267 (27 %)

 

      

eGFR^category, ml/min/m2

≥ 90

60 to < 90

45 to < 60

30 to < 45

15 to < 30

 

76 (3 %)

659 (28 %)

1,346 (57 %)

274 (12 %)

24 (1 %)

 

71 (3 %)

680 (29 %)

1,344 (56 %)

265 (11 %)

19 (1 %) 

 

147 (3 %)

1,339 (28 %)

2,690 (57 %)

539 (11 %)

43 (1 %) 

 

 

      

Albuminuria, mg/mmol, n

< 3

3 to 30

> 30

 

1,369 (58 %)

933 (39 %)

77 (3 %) 

 

1,343 (56 %)

970 (41 %)

66 (3 %)

 

2,712 (57 %)

1,903 (40 %)

143 (3 %)

 

 

      

*NSAID: nonsteroidal anti-inflammatory drug

#PPI: proton pump inhibitor

^eGFR: estimated glomerular filtration rate

Results

Endpoint

CKD, eGFR <60 ml/min/m2or UACR ≥3 mg/mmol

(N=4,758)

No CKD, eGFR ≥60 ml/min/m2 and UACR 3 mg/mmol

(N=13,004)

 p-value
   Aspirin  Placebo HR (95 % CI)  Aspirin Placebo HR (95 % CI)  

Dementia, persistent physical disability, or death

 30.2 % 31.3 %  0.97 (0.83–1.12) 18.6 % 17.8 % 1.05 (0.93–1.18)  0.42

Major adverse cardiovascular events

 11 % 14.2 % 0.77 (0.61–0.99) 6.8 % 6.9 % 0.98 (0.80–1.19) 0.14

Bleeding

 11.7 % 9.1 % 1.28 (0.98–1.68) 7.4 % 5.4 % 1.38 (1.12–1.70) 0.67

Myocardial infarction

 5.8 % 6.2 % 0.94 (0.66–1.33) 3.4 % 3.6 % 0.94 (0.71–1.23) 0.99
Ischemic stroke 4.4 % 7 % 0.63 (0.44–0.91) 3.2 % 3 % 1.10 (0.82–1.47) 0.02
All-cause mortality  19.1 % 17.7 % 1.08 (0.89–1.32) 10.5 % 8.7 % 1.20 (1.02–1.41) 0.43
Cardiovascular mortality 2.6 % 4.2 % 0.63 (0.39–0.99) 1.8 % 1.7 % 1.10 (0.75–1.61)  0.07

CI: confidence interval

Adverse Events

N/A

Study Author Conclusions

Aspirin did not improve outcomes in older people while increasing the risk of bleeding, with mostly consistent effects in participants with and without CKD.

InpharmD Researcher Critique

 This study was a post hoc secondary analysis of ASPREE. Given that the original study was not powered to evaluate the presence of treatment heterogeneity of aspirin in CKD patients, the outcomes of this analysis cannot be considered conclusive and should be interpreted cautiously. 



Table 4 References:
[7] Wolfe R, Wetmore JB, Woods RL, et al. Subgroup analysis of the ASPirin in Reducing Events in the Elderly randomized clinical trial suggest aspirin did not improve outcomes in older adults with chronic kidney disease. Kidney Int. 2021;99(2):466-474. doi:10.1016/j.kint.2020.08.011.

 

Low‑Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors: Subanalysis of a Randomized Clinical Trial (JPPP‑70)

Design

Post hoc subanalysis of the randomized Japanese Primary Prevention Project (NCT00225849)

(N=14,464)

Objective

To investigate whether once-daily low-dose aspirin versus no aspirin reduced the risk of cardiovascular events (CVEs) in patients aged≥70 years with atherosclerotic risk factors 

Study Groups

Aged ≥ 70 years (n = 7,971)

Aged < 70 years (n = 6,493) 

Inclusion Criteria

 Patients who met Japanese criteria for hypertension, dyslipidemia, or diabetes.

Exclusion Criteria

Medical history of coronary artery disease, cerebrovascular disease, atherosclerotic disease, requiring medical or surgical intervention, atrial fibrillation, peptic ulcer, or bleeding disorders or abnormalities (e.g., clotting factor deficiencies); on antiplatelet therapy, anticoagulants, or nonsteroidal anti-inflammatory drugs, or previous adverse reaction to aspirin or salicylic acid.

Methods

Patients were enrolled by their primary care physicians from 1,007 clinics in Japan. During the study period, patients were allowed to take medications to manage hypertension, dyslipidemia, and diabetes according to the Japanese guidelines. Patients were randomized (1:1) to receive either 100 mg enteric-coated aspirin or no aspirin after the initial screening visit. 

At each clinic visit, disease outcomes, adverse events, self-reported treatment adherence, blood pressure, serum lipid levels, blood glucose levels, smoking status, and body weight were evaluated. 

Duration

Data collection: March 2005 to June 2007 

Follow-up: until consent form withdrawal or death (verified by the end of April 2014)

Outcome Measures

Primary outcome: a composite of death from cardiovascular causes (myocardial infarction [MI], stroke, and other cardiovascular causes), nonfatal stroke (ischemic or hemorrhagic, including undefined cerebrovascular events), and nonfatal MI

Secondary outcomes: a composite of the primary outcome plus transient ischemic attack, angina pectoris, and arteriosclerotic disease requiring medical or surgical intervention 

Safety outcomes: incidence of adverse events 

Baseline Characteristics

  

Aged ≥ 70 years

(n=7,971)

Aged < 70 years

(n=6,493) 

p-value

  

Aged ≥ 70 years (n=7,971)
 Aspirin (n=3,986) No aspirin (n=3,985)

p-value

Mean age, years

 75.2 ± 3.9 64.8 ± 2.8 < 0.0001 75.2 ± 3.9 75.2 ± 3.9

0.822

Male

 3,118 (39.1%) 3,005 (46.3%) < 0.0001 1,555 (39%) 1,563 (39.2%) 0.847

Mean BMI, kg/m2

23.9 ± 3.4

 24.5 ± 3.4 < 0.0001

23.9 ± 3.4

 23.9 ± 3.4 0.787

Vascular events risks

HT

DL

DM

DL and DM

HT, DL, and DM

  


6,916 (86.8%)

5,565 (69.8%)

2,597 (32.6%)

1,853 (23.2%)

1,527 (19.2%)

  


5,362 (82.6%)

4,833 (74.4%)

2,306 (35.5%)

1,739 (26.8%)

1,361 (21.0%)

  


< 0.0001

< 0.0001

0.0002

< 0.0001

0.0069

  


3,459 (86.8%)

2,791 (70.0%)

1,297 (32.5%)

928 (23.3%)

765 (19.2%)

  


3,457 (86.8%)

2,774 (69.6%)

1,300 (32.6%)

925 (23.2%)

762 (19.1%)

  


0.970

0.691

0.937

0.942

0.936

Family history of CV

No 

Yes

  


4,497 (56.4%)

2,080 (26.1%)

  


3,647 (56.2%)

1,883 (29.0%)

  


< 0.0001

–

  


2,244 (56.3%)

1,042 (26.1%)

  


2,253 (56.5%)

1,038 (26.0%)

  


0.975

–

Currently smoking

 784 (9.8%) 1,109 (17.1%) < 0.0001

399 (10%)

385 (9.7%)

 0.601

Mean Laboratory values

Systolic BP, mmHg

Total Cholesterol, mg/dL

Low-density lipoproteina

High-density lipoprotein

HbA1c, %b

 

137.7 ± 15.3

200.7 ± 32.4

118.3 ± 29.8

57.5 ± 15.3

5.6 ± 0.9

 

136.5 ± 16.1

206.4 ± 32.9 

121.0 ± 31.1

58.6 ± 16.3

5.7 ± 1.1

  


< 0.0001

< 0.0001

< 0.0001

< 0.0001

< 0.0001

  


137.6 ± 15.3

200.4 ± 32.5

118.1 ± 29.7

57.3 ± 15.4

5.6 ± 0.9

  


137.9 ± 15.4

201.0 ± 32.3

118.5 ± 29.9

57.8 ± 15.1

5.7 ± 1.1



0.39

0.42

0.551

0.162

< 0.0001

SI conversion factors: To convert total, low-density lipoprotein, and high-density lipoprotein cholesterol to mmol/L, multiply by 0.0259; to con- vert triglycerides to mmol/L, multiply by 0.0113; to convert glucose to mmol/L, multiply by 0.0555.

BMI body mass index (calculated as weight in kg divided by height in m2), CV cardiovascular, DL dyslipidemia, DM diabetes mellitus, HbA1c glycated hemoglobin, HT hypertension, SD standard deviation.

aCalculated based on the Friedewald formula and direct measurements.

bNational Glycohemoglobin Standardization Program method.

Results

 

Primary events 

Event rate/1,000 person-years 

  

 

    

Aged ≥ 70 years

Men

Women

Total

Aspirin 

Non-aspirin



144

151

295

141

154



10.01

6.62

7.93

7.60

8.25

        

Aged < 70 years 

Men 

Women 

Total



69

36

105

 

4.9

2.15

3.41

        

Composite of primary and secondary outcomes 

 

Aged < 70 years

 Aged ≥ 70 years Interaction p-valuea  

Aspirin

(n=3,234)

Non-aspirin

(n=3,259)

Aspirin

(n=3,986)

Non-aspirin

 (n=3,985)

    

Primary endpoint 

Fatal:nonfatal events

Cerebral infarction

Intracranial hemorrhage

SAH

Myocardial infarction

Other fatal or nonfatal cardiovascular events

  

10:42

1:24

0:6

1:4

3:7

5:1

  

10:43

2:27

0:4

0:0

3:9

5:3

  

46:95

1:59

5:17

1:4

4:13

35:2

  

46:108

5:67

5:6

4:4

6:29

26:2


-

-

-

-

-

- 

  

Total primary events

  52 53 141 154 0.745  

Total secondary events (first event)b

 310 (181) 302 (172) 606 (370) 679 (399) - (0.300)  

Aged ≥ 70 years: hazard ratio (HR) of the primary outcome 0.92 (95% CI 0.74–1.16; P = 0.50) vs. no-aspirin

HDL < 40 mg/dL: HR of the primary endpoint 0.44 (95% CI 0.20–0.93; P = 0.03) vs. no-aspirin

HDL < 40 mg/dL, smoking, or having diabetes mellitus were risk factors associated with the primary outcome.  

No significant differences were noted in secondary outcomes between < 70 years vs. ≥ 70 years.        

SAH = Subarachnoid hemorrhage

aTest for heterogeneity among treatment vs control hazard ratios between patients aged≥70 years and those aged<70 years

bOwing to some patients experiencing multiple secondary events in this study, the test for heterogeneity was performed using data on those secondary events that occurred first in each patient

Adverse Events

Gastrointestinal adverse events in patients aged ≥ 70 years (aspirin vs. no-aspirin), p-value < 0.0001: 

Stomach/abdominal discomfort 199 (5%) vs. 95 (2.4%), gastroduodenal ulcer 106 (2.7%) vs. 46 (1.2%), stomach/abdominal pain 78 (2%) vs. 33 (0.8%), gastrointestinal bleeding 63 (1.6%) vs. 18 (0.5%)

Serious Adverse Events (aspirin vs. no-aspirin): Fatal ICH: 5 vs. 5; nonfatal ICH: 17 vs. 6; severe extracranial hemorrhage requiring hospitalization or transfusion: 0 vs. 1

Study Author Conclusions

Aspirin did not reduce the risk of primary or secondary outcomes in old patients. Aspirin treatment may have reduced CVEs within a high CVE risk elderly population subgroup. Aspirin treatment in such a group requires caution, because of the increased risk of intracranial hemorrhage, severe extracranial hemorrhage requiring hospitalization or transfusion, and gastrointestinal bleeding in old patients receiving aspirin therapy.

InpharmD Researcher Critique

Similar to the original study, the subgroup analysis was prematurely terminated due to low rates of events and likely futility. The open-label nature of this trial might lead to falsely elevated adverse events among the active treatment group with aspirin. Even though the primary prevention with aspirin appeared beneficial in a subgroup mainly consisted of male patients aged ≥ 70 years with HDL levels of < 40 mg/dL, this exploratory data is based on a very small cohort (3.5% of the original study population).

 



Table 5 References:
[8] Sugawara M, Goto Y, Yamazaki T, et al. Low-dose aspirin for primary prevention of cardiovascular events in elderly Japanese patients with atherosclerotic risk factors: subanalysis of a randomized clinical trial (JPPP-70). Am J Cardiovasc Drugs. 2019;19(3):299-311. doi:10.1007/s40256-018-0313-0.