A 55-year-old male with PMHx of type II diabetes mellitus, current smoker of 15 pack years, presents to you with a question of daily low dose aspirin as prevention as they are concerned about their risk of heart attack, stroke, and cardiovascular disease in general, but had heard of recent change in recommendations regarding daily aspirin use. Their diabetes is well controlled but have struggled to quit smoking cigarettes over the years. You calculate their AHA/ACC 10-year risk of a cardiovascular event to be 16.6% but are unsure of the most recent recommendation and how to best educate the patient.
Search Question:
Is daily low dose aspirin beneficial as primary prevention in adults at increased risk of a cardiovascular event?
PICO Search Terms:
| P | I | C | O |
| Males over 50 | Daily aspirin | Placebo | Decreased CVD risk |
| Moderate CVD risk | Low-dose aspirin | No intervention | Decreased MI risk |
| Controlled diabetics | 81 mg aspirin | Without aspirin | Decreased stroke risk |
| Smokers | Aspirin prevention | No daily aspirin | Decreased ASCVD risk |
Search Strategy:
Since this is investigating a treatment/prevention, a search for meta-analyses / systematic reviews would result in the best evidence. Randomized control trials and retrospective cohort studies are also considered for inclusion as they are the next best standard of evidence after the aforementioned gold standard and are appropriate to an investigation of prevention / treatment options. The articles were selected based on how current they were balanced with how closely their patient selection paralleled the patient proposed in the PICO.
Results found:
| Database | Filter | Terms Searched | Articles Returned |
| PubMed | Meta-analysis / rct / systematic review Last 10 years English Full text Middle aged 45-64 | “aspirin primary prevention cardiovascular” | 184 |
| Cochrane Library | Cochrane reviews Last 10 years | “aspirin primary prevention cardiovascular” | 5 |
| Google Scholar | Last 5 years Review articles | “aspirin primary prevention cardiovascular diabetes” | 3,460 |
Articles chosen:
Article 1
| US Preventive Services Task Force, Davidson KW, Barry MJ, et al. 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 |
| Type of Study: Systematic review |
| IMPORTANCE Cardiovascular disease (CVD) is the leading cause of mortality in the US, accounting for more than 1 in 4 deaths. Each year, an estimated 605 000 people in the US have a first myocardial infarction and an estimated 610 000 experience a first stroke. OBJECTIVE To update its 2016 recommendation, the US Preventive Services Task Force (USPSTF) commissioned a systematic review on the effectiveness of aspirin to reduce the risk of CVD events (myocardial infarction and stroke), cardiovascular mortality, and all-cause mortality in persons without a history of CVD. The systematic review also investigated the effect of aspirin use on colorectal cancer (CRC) incidence and mortality in primary CVD prevention populations, as well as the harms (particularly bleeding) associated with aspirin use. The USPSTF also commissioned a microsimulation modeling study to assess the net balance of benefits and harms from aspirin use for primary prevention of CVD and CRC, stratified by age, sex, and CVD risk level. POPULATION Adults 40 years or older without signs or symptoms of CVD or known CVD (including history of myocardial infarction or stroke) who are not at increased risk for bleeding (eg, no history of gastrointestinal ulcers, recent bleeding, other medical conditions, or use of medications that increase bleeding risk). EVIDENCE ASSESSMENT The USPSTF concludes with moderate certainty that aspirin use for the primary prevention of CVD events in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk has a small net benefit. The USPSTF concludes with moderate certainty that initiating aspirin use for the primary prevention of CVD events in adults 60 years or older has no net benefit. RECOMMENDATION The decision to initiate low-dose aspirin use for the primary prevention of CVD in adults aged 40 to 59 years who have a 10% or greater 10-year CVD risk should be an individual one. Evidence indicates that the net benefit of aspirin use in this group is small. Persons who are not at increased risk for bleeding and are willing to take low-dose aspirin daily are more likely to benefit. (C recommendation) The USPSTF recommends against initiating low-dose aspirin use for the primary prevention of CVD in adults 60 years or older. (D recommendation) |
| Reason for Selection: This article was chosen as it is extremely recent and directly reflects the most recent new guidelines on daily low dose aspirin use by the USPSTF. It is a systematic review published by the reputable JAMA with results that directly address the risks and benefits of aspirin use for this PICOs patient in question. |
| Key Points: – Concludes with moderate certainly that aspirin for primary CVD events prevention in patients 40-59 years old with >10% 10-year CVD risk had a small net benefit – Aspirin use for primary prevention of CVD events in those >60 years old had no net benefit – Risk factors for bleeding: age, male sex, diabetes, history of GI issues such as PUD, liver disease, smoking, and hypertension. – Benefits appear similar from low dose (<100 mg/d) to all other doses, 81 mg/d is a ‘pragmatic’ approach – For adults 40-59 years old with 10% or greater estimated CVD risk there is a grade C recommendation for daily aspirin, and grade D for those over the age of 60 – USPSTF related recommendations include smoking cessation, statin use, healthy diet, healthy weight, and activity |
Article 2
| Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis [published correction appears in JAMA. 2019 Jun 11;321(22):2245]. JAMA. 2019;321(3):277-287. doi:10.1001/jama.2018.20578 |
| Type of Study: Systematic Review and Meta-analysis |
| Importance: The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.Objective: To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.Data sources: PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.Study selection: Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).Data extraction and synthesis: Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.Main outcomes and measures: The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).Results: A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).Conclusions and relevance: The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding. |
| Reason for Selection: Includes mention of studies of specifically patients with diabetes patients at both either high or low risk of CVD events (low=<10%, high=>10%). This article is a meta-analysis, and thus chosen for being of the highest level of evidence. |
| Key Points:- Use of aspirin in those with no history or current CVD was associated with lower risk of CVD events, although with an increase in risk of major bleeding- Aspirin use associated with increase in major bleeding (HR 1.29) GI bleeding (HR 1.35) but not intracranial bleeding- Aspirin use associated with reductions in primary CVD and increases in major bleeding risks in both low and high CV risk populations with diabetes- Cardiovascular risk scores tends to overestimate an individual’s true risk, with poor agreement between different CV risk calculators |
Article 3:
| Judge C, Ruttledge S, Murphy R, et al. Aspirin for primary prevention of stroke in individuals without cardiovascular disease-A meta-analysis. Int J Stroke. 2020;15(1):9-17. doi:10.1177/1747493019858780 |
| Type of Study: Meta-analysis |
| Background: The benefits of aspirin for primary prevention of stroke are uncertain.Methods: We performed a cumulative meta-analysis of trials investigating aspirin for primary prevention of cardiovas- cular disease with a focus on stroke. We assessed the effects of aspirin on non-fatal stroke, hemorrhagic stroke, non-fatal myocardial infarction, all-cause mortality, cardiovascular mortality, major gastrointestinal bleeding, and an analysis of net clinical effect, in populations without a history of clinical or subclinical cardiovascular disease.Summary of review results: Among 11 trials (157,054 participants), aspirin was not associated with a statistically significant reduction in non-fatal stroke (odds ratio, 0.94; 95% CI, 0.85 to 1.04) but was associated with an increased risk of hemorrhagic stroke (odds ratio, 1.29; 95% CI, 1.06 to 1.56). Aspirin was not associated with a statistically significant reduction in all-cause mortality (odds ratio, 0.97; 95% CI, 0.92 to 1.03) or cardiovascular mortality (odds ratio, 0.94; 95% CI, 0.85 to 1.03). Aspirin was associated with a reduction in non-fatal myocardial infarction (odds ratio, 0.80; 95% CI, 0.69 to 0.94) and an increased risk of major gastrointestinal bleeding (odds ratio, 1.83; 95% CI, 1.43 to 2.35). Using equal weighting for non-fatal events and major bleeding, we observed no net clinical benefit with aspirin use for primary prevention.Conclusion: Our meta-analysis reports no benefit of aspirin for primary stroke prevention. |
| Reason for Selection: Chosen for being a meta-analysis while also addressing the patients concerns of stroke. With 11 trials of over 150,000 participants this is a substantial systematic review / meta-analysis. |
| Key Points:– No statistically significant decreased risk of non-fatal stroke– Significant increase in hemorrhagic stroke (OR 1.29)– No significant benefit to all-cause mortality– Statistically significant decreased risk of non-fatal MI (OR 0.80) – Net-benefit analysis showed no significant effect of aspirin on the composite of all-cause mortality, non-fatal stroke, non-fatal myo- cardial infarction and major bleeding |
Article 4:
| Barbarawi M, Kheiri B, Zayed Y, et al. Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials. High Blood Press Cardiovasc Prev. 2019;26(4):283-291. doi:10.1007/s40292-019-00325-5 |
| Type of Study: Meta-analysis |
| Introduction: The role of aspirin as a means of primary prevention remains controversial.Aim: We have conducted a meta-analysis of all randomized controlled trials (RCTs) to evaluate the role of aspirin in primary prevention.Methods: Literature search was performed via PubMed, Embase, and the Cochrane Library for all related RCTs. All-cause mortality was the primary endpoint. Secondary endpoints included major adverse cardiovascular events (MACE), myocardial infarction (MI), cardiovascular mortality, cerebrovascular events, and bleeding events. We used a random effects model to report the risk ratios (RRs) with 95% confidence intervals (CIs).Results: Our analysis included 17 RCTs (164,862 patients; 83,309 received aspirin and 81,744 received placebo). Our study did not demonstrate any significant reduction in all-cause mortality for patients treated with aspirin when compared with placebo (RR 0.97; 95% CI 0.93-1.01; P = 0.13). Sensitivity analysis performed by excluding healthy elderly (≥ 65) showed significant reductions in all-cause mortality in the aspirin-treated patients (RR 0.94; 95% CI 0.90-0.99; P = 0.01). There were no significant differences between both groups regarding cardiovascular mortality and cerebrovascular events (P > 0.05). However, aspirin-treated patients significantly reduced MACE and MI events (RR 0.89; 95% CI 0.85-0.93; P < 0.001 and RR 0.88; 95% CI 0.78-0.98; P = 0.02, respectively), respectively. However, aspirin was associated with a significantly higher incidence of bleeding, including major bleeding and intracranial bleeding (P < 0.001).Conclusions: Aspirin use in primary prevention has resulted in a lower incidence of MACE and MI without significantly effecting cerebrovascular events. However, aspirin was associated with a higher bleeding risk. Use of aspirin as a means of primary prevention should be thoroughly discussed with patients and pursued based on the risk of cardiovascular disease while also considering bleeding risk. |
| Reason for Selection: Again, meta-analyses were preferred for being of the highest quality of evidence and this article was no exception. The study additionally had a subset analysis of diabetic patients which addresses the concerned patient’s chronic health issues. |
| Key Points:– Aspirin had no effect on all cause mortality (including CV mortality and CVAs)– Aspirin was associated with lower MACE and MI– Aspirin was associated with significant increase in all bleeding events, including both major bleeding and intracranial bleeding– Current guidelines state that there is insufficient data supporting use of aspirin as primary prevention– A subset analysis of diabetic patients was unable to establish significant benefit of aspirin over placebo, although aspirin treated patients had an increased risk of intracranial hemorrhage |
Article 5
| ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus. N Engl J Med. 2018;379(16):1529-1539. doi:10.1056/NEJMoa1804988 |
| Type of Study: Randomized Control Trial |
| Background: Diabetes mellitus is associated with an increased risk of cardiovascular events. Aspirin use reduces the risk of occlusive vascular events but increases the risk of bleeding; the balance of benefits and hazards for the prevention of first cardiovascular events in patients with diabetes is unclear.Methods: We randomly assigned adults who had diabetes but no evident cardiovascular disease to receive aspirin at a dose of 100 mg daily or matching placebo. The primary efficacy outcome was the first serious vascular event (i.e., myocardial infarction, stroke or transient ischemic attack, or death from any vascular cause, excluding any confirmed intracranial hemorrhage). The primary safety outcome was the first major bleeding event (i.e., intracranial hemorrhage, sight-threatening bleeding event in the eye, gastrointestinal bleeding, or other serious bleeding). Secondary outcomes included gastrointestinal tract cancer.Results: A total of 15,480 participants underwent randomization. During a mean follow-up of 7.4 years, serious vascular events occurred in a significantly lower percentage of participants in the aspirin group than in the placebo group (658 participants [8.5%] vs. 743 [9.6%]; rate ratio, 0.88; 95% confidence interval [CI], 0.79 to 0.97; P=0.01). In contrast, major bleeding events occurred in 314 participants (4.1%) in the aspirin group, as compared with 245 (3.2%) in the placebo group (rate ratio, 1.29; 95% CI, 1.09 to 1.52; P=0.003), with most of the excess being gastrointestinal bleeding and other extracranial bleeding. There was no significant difference between the aspirin group and the placebo group in the incidence of gastrointestinal tract cancer (157 participants [2.0%] and 158 [2.0%], respectively) or all cancers (897 [11.6%] and 887 [11.5%]); long-term follow-up for these outcomes is planned.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. (Funded by the British Heart Foundation and others; ASCEND Current Controlled Trials number, ISRCTN60635500 |
| Reason for Selection: Being a systematic review makes the study of high level of evidence while also being relatively recent (2018 publication) and published in the esteemed New England Journal of Medicine. |
| Key Points:– Aspirin at dose of 100 mg daily for 7.4 years resulted in 12% lower risk of serious CVD events but also risk of major bleeding was 29% higher (in patients with diabetes and no evident CVD at trial entry)– Assessing risk to benefit is complicated by comparison of severity of CVD events and severity of bleeding events– Approximately half of excess bleeding was in the GI tract, and ⅓ in the upper GI tract– Bleeding rates may be lower if PPIs were routinely used, but this point requires further research |
Summary of the Evidence:
| Author (Date) | Level of Evidence | Sample / Setting | Outcome(s) Studied | Key Findings | Limitations and Biases |
| Davidson, K. W., Barry, M. J., Mangione, C. M., Cabana, M., Chelmow, D., Coker, T. R., Davis, E. M., Donahue, K. E., Jaén, C. R., Krist, A. H., Kubik, M., Li, L., Ogedegbe, G., Pbert, L., Ruiz, J. M., Stevermer, J., Tseng, C. W., & Wong, J. B. (2022) | Systematic Review | 13 Randomized Control Trials 161,680 participants | Efficacy as primary prevention of cardiovascular morbidity and mortality | – Concludes with moderate certainly that aspirin for primary CVD events prevention in patients 40-59 years old with >10% 10-year CVD risk had a small net benefit– Aspirin use for primary prevention of CVD events in those >60 years old had no net benefit– Risk factors for bleeding: age, male sex, diabetes, history of GI issues such as PUD, liver disease, smoking, and hypertension.- Benefits appear similar from low dose (<100 mg/d) to all other doses, 81 mg/d is a ‘pragmatic’ approach- For adults 40-59 years old with 10% or greater estimated CVD risk there is a grade C recommendation for daily aspirin, and grade D for those over the age of 60USPSTF related recommendations include smoking cessation, statin use, healthy diet, healthy weight, and activity | “Concerns about calibration exist, with many external validation studies showing overprediction in broad populations (men and women across racial and ethnic groups).5-7 Limited evidence also suggests underprediction in disadvantaged communities8,9 that could lead to underutilization of preventive therapies. Clinicians should recognize that predictions of 10-year CVD events using the Pooled Cohort Equations are estimates.” |
| Zheng, S. L., & Roddick, A. J. (2019) | Meta-analysis | 13 trials of 164,225 participants | CV mortality, nonfatal MI, and nonfatal stroke outcomes vs major bleeding | – Use of aspirin in those with no history or current CVD was associated with lower risk of CVD events, although with an increase in risk of major bleeding- Aspirin use associated with increase in major bleeding (HR 1.29) GI bleeding (HR 1.35) but not intracranial bleeding- Aspirin use associated with reductions in primary CVD and increases in major bleeding risks in both low and high CV risk populations with diabetesCardiovascular risk scores tends to overestimate an individual’s true risk, with poor agreement between different CV risk calculators | Availability and quality of evidence End point definitions between trials differed Daily doses of aspirin varied between studies |
| Judge, C., Ruttledge, S., Murphy, R., Loughlin, E., Gorey, S., Costello, M., Nolan, A., Ferguson, J., Halloran, M. O., O’Canavan, M., & O’Donnell, M. J. (2020) | Meta-analysis | 11 trials Over 150,00 participants | Non-fatal stroke Hemorrhagic stroke All cause mortality Cardiovascular mortality | – No statistically significant decreased risk of non-fatal stroke- Significant increase in hemorrhagic stroke (OR 1.29)- No significant benefit to all-cause mortality- Statistically significant decreased risk of non-fatal MI (OR 0.80) – Net-benefit analysis showed no significant effect of aspirin on the composite of all-cause mortality, non-fatal stroke, non-fatal myo- cardial infarction and major bleeding | 2 studies did not report stroke outcome 3 studies did not require imaging for diagnosis of stroke |
| Barbarawi, M., Kheiri, B., Zayed, Y., Gakhal, I., Al-Abdouh, A., Barbarawi, O., Rashdan, L., Rizk, F., Bachuwa, G., & Alkotob, M. L. (2019) | Meta-analysis | 17 RCTs 164,862 patients | All-cause mortality CV mortality Cerebrovascular events MACE/MI events | – Aspirin had no effect on all cause mortality (including CV mortality and CVAs)- Aspirin was associated with lower MACE and MI- Aspirin was associated with significant increase in all bleeding events, including both major bleeding and intracranial bleeding- Current guidelines state that there is insufficient data supporting use of aspirin as primary preventionA subset analysis of diabetic patients was unable to establish significant benefit of aspirin over placebo, although aspirin treated patients had an increased risk of intracranial hemorrhage | Heterogenous inclusion criteria Adherence rate of aspirin was 70% which may underestimate aspirin efficacy Without patient-level data unable to determine efficacy in low vs moderate vs high risk patients |
| ASCEND Study Collaborative Group, Bowman, L., Mafham, M., Wallendszus, K., Stevens, W., Buck, G., Barton, J., Murphy, K., Aung, T., Haynes, R., Cox, J., Murawska, A., Young, A., Lay, M., Chen, F., Sammons, E., Waters, E., Adler, A., Bodansky, J., Farmer, A., … Armitage, J. (2018) | Randomized Control Trial | 15,480 participants Mean follow up of 7.4 years | Primary efficacy outcome was first serious vascular event Primary safety outcome was the first major bleeding even | – Aspirin at dose of 100 mg daily for 7.4 years resulted in 12% lower risk of serious CVD events but also risk of major bleeding was 29% higher (in patients with diabetes and no evident CVD at trial entry)- Assessing risk to benefit is complicated by comparison of severity of CVD events and severity of bleeding events- Approximately half of excess bleeding was in the GI tract, and ⅓ in the upper GI tract – Bleeding rates may be lower if PPIs were routinely used, but this point requires further research | Mean adherence of 70% in both aspirin and placebo groups |
Conclusion(s):
Article 1 et al concluded that there was small net benefit in patients 40-59 years old who had a cardiovascular disease (CVD) event risk of over 10%. The patient concerned in the question fits into this risk category. Our patient is also a current cigarette smoker who is recommended by this article to quit smoking as soon as possible to help reduce their risk category. Article 2 et al determined that, in patients with no CVD history, aspirin also reduced the risk of future events. This comes at the cost of an increased risk of bleeding with a hazard ratio of 1.29. Gastrointestinal bleeding was the most common form of bleed, with it’s hazard ratio being 1.35. Article 3 et al did not find any significantly decreased risk of CVD events such as non-fatal strokes in low-dose aspirin use in this population while also finding an increased risk of hemorrhagic strokes. However, they did find a statistically significant reduction in non-fatal myocardial infarctions. Article 4 et al, found findings similar to the previously mentioned study, with the addition of a subset of diabetic patients. A 12% decrease in serious CVD events was noted, with a 29% increase in major bleeding risk occurring most often in the GI tract. Article 5 et al, supported the findings of most of the previous studies, when specifically pertaining to diabetic patients, by concluding that the benefits of aspirin in this population were counterbalanced by an increased risk of bleeding. The general conclusion from gathering all of this evidence would be the same, that it would be difficult to justify daily low-dose aspirin in this patient when weighing the risks against the benefits.
Clinical Bottom Line:
The clinical bottom line is that these studies, of the highest standard and very recent publication, would make it difficult to recommend to the patient in question a daily regimen of low-dose aspirin. This is supported by the latest USPSTF points found in the updated guidelines. The benefit of aspirin weighed against the risk of major bleeding is difficult to justify especially with diabetic patients who are already at an increased risk of bleeding to begin with. Additionally, this patient would no longer be recommended to take daily aspirin despite their moderate risk in just 5 years.
- Zheng SL, Roddick AJ. Association of Aspirin Use for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-analysis
I would select this as my number 1 study as it was published very recently in JAMA and includes a great number of participants (164,225) and a median age of participants closely resembling the patient in question. The study additionally mentions specifically patients who are diabetic with either a low or high risk of CVD events.
2. US Preventive Services Task Force, Davidson KW, Barry MJ, et al. Aspirin Use to Prevent Cardiovascular Disease: US Preventive Services Task Force Recommendation Statement.
This was selected as my number two choice as it is of extremely recent publication and reflects the guidelines most recently published by the USPSTF. Being a systematic review it is of very high level of evidence and published by the reputable JAMA with results that evaluate the risks versus benefits of aspirin use for the type of patient in question.
3. Barbarawi M, Kheiri B, Zayed Y, et al. Aspirin Efficacy in Primary Prevention: A Meta-analysis of Randomized Controlled Trials.
This meta-analysis was excellent for its inclusion of diabetic patients which suits the patient in the PICO question. Their main endpoint was all-cause mortality with secondary endpoints of cardiovascular events, CV mortality, MI, and bleeding events. The study included 4049 studies initially, excluded 3886 studes, with remaining 158 trials, and 17 RCTs included in the final analysis.
4. Judge C, Ruttledge S, Murphy R, et al. Aspirin for primary prevention of stroke in individuals without cardiovascular disease-A meta-analysis.
Selected for being a cumulative meta-analysis that extracted data from multiple meta-analyses. It integrated two separate analyses of the efficacy of aspirin for primary prevention of cardiovascular disease and the risk of bleeding. While the study makes mention of the high quality of either integrated meta-analysis they also acknowledge that neither were repeated by themselves which prevents this study from being a top choice.
5. ASCEND Study Collaborative Group, Bowman L, Mafham M, et al. Effects of Aspirin for Primary Prevention in Persons with Diabetes Mellitus.
This study was chosen for it’s specific focus on patients with diabetes mellitus. Men and women over the age of 40 were selected if they had a diagnosis of diabetes mellitus and had no CVD. The study used minimized randomization for patients to either receive 100 mg aspirin or placebo. Given that the adherence was only 70% in both groups and that this number declined over the course of follow-ups, there are some clear limitations of the study.
Magnitude of any effects:
The magnitude of effect is reasonably high, as most studies reported a decrease in significant cardiovascular events. This has to be considered along with the fact there is, across the board, findings of increased significant bleeding as a result of this therapy and that the latest USPSTF recommendations do not support low dose aspirin use after the age of 60, and even the recommendation for those under 60 is a grade ‘C’ recommendation.
Any other considerations important in weighing this evidence to guide practice
When weighing this evidence it’s important to remember that the USPSTF does in fact make a recommendation, albeit not a particularly strong one, for low-dose aspirin use for primary CVD prevention in adults 40-59. That being said the decision to do so ‘should be an individual one’, while those over 60 there is a grade ‘D’ recommendation to not initiate aspirin for CVD prevention at all. While the evidence did not convince in the case of the patient in question here, in those with no history or predisposition for bleeds (such as gastric ulcers or certain medications) there is still a recommendation for it’s use if in the appropriate age range and there is a CVD risk 10% or greater. It’s important to use shared decision making the decision to initiate daily low-dose aspirin in patients and a thorough discussion of risks and benefits is required.
