Is Aspirin Still Necessary for Primary Prevention?

Once hailed as a “miracle pill,” aspirin has long been a cornerstone in cardiovascular prevention. For decades, low-dose aspirin was a routine prescription for seemingly healthy adults to prevent their first heart attack or stroke. It became almost a reflex in primary care. But over time, as more nuanced evidence emerged, so did the questions.

Is aspirin still necessary—or even safe—for primary prevention? Or has it quietly become obsolete in favor of more individualized strategies?

This article dives deep into the evolving evidence, shifting recommendations, and critical clinical considerations for physicians weighing aspirin’s role in modern preventive medicine.

1. A Brief History: Aspirin’s Rise in Cardiovascular Medicine

Aspirin’s journey in cardiovascular care began in earnest during the 1980s and 1990s when several landmark trials demonstrated that it could reduce the incidence of nonfatal myocardial infarction in at-risk populations. Its antiplatelet mechanism offered a cheap, accessible way to prevent thrombotic events.

By the early 2000s, aspirin was widely used in patients:

• With diabetes
  
  
• With hypertension or dyslipidemia
  
  
• Over 50 with any cardiovascular risk factor
  
  
• Without documented cardiovascular disease
  

The prescription was so universal that patients began taking it on their own, assuming its safety outweighed any potential harm. Unfortunately, this widespread adoption outpaced the growth of long-term evidence on its safety profile.

As data from large-scale trials accumulated, a troubling trend emerged—especially in primary prevention. The risks, particularly bleeding complications, began to cast a long shadow over the presumed benefits.

2. Understanding Primary vs. Secondary Prevention

Before delving into the latest data, it’s critical to distinguish between two concepts:

• Primary prevention: Preventing the first cardiovascular event in a patient with no history of myocardial infarction, stroke, or peripheral arterial disease.
  
  
• Secondary prevention: Preventing subsequent events in patients with known atherosclerotic cardiovascular disease (ASCVD).
  

This article focuses solely on aspirin’s role in primary prevention.

In secondary prevention, aspirin continues to play a vital role and is still recommended unless contraindications exist.

3. The Turning Point: Landmark Trials That Shifted the Paradigm

Three major randomized controlled trials published in 2018 fundamentally reshaped the narrative on aspirin in primary prevention.

ARRIVE Trial
This trial enrolled moderate-risk individuals without existing ASCVD.
Findings: No significant reduction in major cardiovascular events.
Risks: Increased incidence of gastrointestinal bleeding.

ASCEND Trial
Focused on diabetic patients without established ASCVD.
Findings: Slight reduction in vascular events—but this was counterbalanced by a significant increase in serious bleeding events.
Conclusion: Marginal net benefit.

ASPREE Trial
Examined healthy individuals over the age of 70.
Findings: No cardiovascular benefit, but an increase in all-cause mortality—largely attributed to bleeding and cancer-related deaths.
Message: Aspirin may not be benign, even in so-called “ideal” candidates.

These trials collectively challenged the long-standing assumption that low-dose aspirin could safely be used as a universal primary prevention tool.

4. Updated Guidelines: A Major Paradigm Shift

Major medical organizations responded swiftly to the shifting evidence with updated recommendations.

U.S. Preventive Services Task Force (USPSTF) – 2022 Update

• No longer recommends routine aspirin use for adults over 60 for primary prevention.
  
  
• For individuals aged 40–59 with a 10-year CVD risk ≥10%: The decision should be individualized, factoring in bleeding risk and patient preference.
  

ACC/AHA Guidelines – 2019

• Aspirin may be considered for adults aged 40–70 with elevated cardiovascular risk and no increased bleeding risk.
  
  
• It should not be used routinely in patients over 70 or in those with increased bleeding risk.
  

The age of "aspirin for all" is decisively over. What remains is a selective, case-by-case framework that prioritizes individualized risk-benefit assessment.

5. The Real Risks: Understanding the Trade-Off

Aspirin’s benefits in primary prevention are modest at best. It reduces the risk of:

• Nonfatal myocardial infarction
  
  
• Ischemic stroke
  

However, it does not reduce all-cause mortality.

On the flip side, the bleeding risks are substantial, particularly:

• Gastrointestinal bleeding
  
  
• Intracranial hemorrhage
  
  
• Minor but recurrent bleeding episodes such as epistaxis or hematuria, especially in older adults
  

Quantitatively, the picture becomes even more sobering:

• Number needed to treat (NNT) to prevent one major cardiovascular event: 250–300
  
  
• Number needed to harm (NNH) via major bleeding: 200–250
  

In essence, for every one patient who may benefit, another is equally likely to suffer a serious adverse effect.

6. Special Populations: Who Might Still Benefit?

While the general consensus is moving away from routine aspirin use, there are specific groups in which it may still have a place.

1. Diabetics with multiple uncontrolled risk factors
   Especially if LDL cholesterol remains high or there’s a strong family history of early-onset cardiovascular disease.
   
   
2. Patients with elevated coronary artery calcium (CAC) scores
   A CAC score above 100 may signify a higher atherosclerotic burden where aspirin’s benefits could outweigh its bleeding risks.
   
   
3. Patients who are statin-intolerant
   For those who cannot take statins, aspirin might serve as a secondary option for risk reduction—though this is controversial.
   
   
4. Smokers or patients with systemic inflammatory disorders
   Conditions like rheumatoid arthritis or lupus may contribute to elevated cardiovascular risk that aspirin could potentially mitigate.
   

Still, even in these scenarios, a thorough conversation around bleeding risk, gastrointestinal history, and concurrent medications (like NSAIDs or steroids) is mandatory.

7. Beyond Aspirin: Emerging Strategies in Cardiovascular Prevention

As aspirin’s role diminishes, attention is turning to alternative—often more effective—approaches:

• Statins: Now considered the cornerstone of cardiovascular risk reduction in primary prevention.
  
  
• Blood pressure control: Especially with agents that offer vascular protection such as RAAS blockers and calcium channel antagonists.
  
  
• Lifestyle interventions: Including dietary modification, smoking cessation, and regular physical activity.
  
  
• Glycemic control: Particularly in diabetics, as part of an integrated cardiovascular risk management strategy.
  
  
• Risk calculators: Tools like the ASCVD risk score help guide personalized decision-making rather than blanket protocols.
  

What’s emerging is a model of precision prevention—where decisions are tailored, risks are weighed, and guidelines are used as frameworks, not rules.

8. Practical Clinical Considerations for Physicians

When a patient asks about starting or continuing aspirin, here are the key considerations:

• What is their 10-year ASCVD risk score?
  
  
• Do they have a history of GI ulcers, easy bruising, or anemia?
  
  
• Are they concurrently on NSAIDs, anticoagulants, or corticosteroids?
  
  
• Are they over age 70 or already using a PPI?
  
  
• Do they understand the relative risks and benefits?
  

This is not a “one-size-fits-all” conversation. It requires shared decision-making, supported by transparent discussions and up-to-date guidelines.

Importantly, patients who are already on aspirin—often without a clear indication—should be reevaluated. If the rationale no longer holds, deprescribing should be considered.

9. Deprescribing Aspirin: A Clinical Art

Deprescribing can be harder than prescribing, particularly for a drug long believed to be a lifesaver.

• Never stop aspirin abruptly in patients using it for secondary prevention.
  
  
• For primary prevention, no taper is needed—but discussions should be evidence-based.
  
  
• Reassure patients: Stopping aspirin often leads to fewer bleeding complications without significantly raising cardiac risk.
  
  
• In patients who must remain on aspirin, consider adding a proton pump inhibitor for GI protection.
  
  
• Use decision aids and visual tools to facilitate understanding and reduce anxiety about medication changes.
  

Ultimately, deprescribing should be framed as an act of proactive care—not withdrawal.

10. Conclusion: Personalized Prevention Is the Future

We are witnessing the end of an era.

Aspirin is no longer the universally prescribed “miracle drug” in primary prevention. Instead, we are entering a time of precise, data-driven, and patient-centered care. Physicians are expected to act not just as prescribers, but as educators and risk navigators.

In 2025 and beyond, the better approach to preventing a first cardiovascular event may not lie in a single pill—but in a customized regimen that addresses the root causes of risk.

• Lifestyle changes
  
  
• Lipid and glucose control
  
  
• Hypertension management
  
  
• Risk stratification
  

Aspirin? Perhaps—but only when the math, the data, and the patient agree.