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Welcome to Core IM, a virtual medical community! Core IM strives to empower its colleagues of all levels and backgrounds with clinically applicable information as well as inspire curiosity and critical thinking. Core IM promotes its mission through podcasts and other multimodal dialogues. ACP has teamed up with Core IM to offer continuing medical education, available exclusively to ACP members by completing the CME/MOC quiz.

1. Q1: “Have you been getting questions about aspirin?”
   1. Patients are hearing about aspirin from a variety of sources differing drastically in credibility: USPSTF? The ? Friends and family?
   2. As clinicians practicing evidence-based medicine, what is our best approach to educating patients about aspirin?
2. Q2: “What do the guidelines say about aspirin’s role in primary prevention?”
   1. 1. For patients aged 40-70 years, aspirin should be used infrequently for primary prevention [IIb recommendation]
      2. For patients aged >70 years, the evidence does not support the use of aspirin for routine primary prevention [class III recommendation]
   2. 1. For patients aged 40-59 years with a 10-year ASCVD risk >10%, starting aspirin for primary prevention should be discussed as a shared decision (grade C)
      2. For patients aged >60 years: do not initiate aspirin for primary prophylaxis (grade D)
3. Q3: “Why and how does aspirin work?”
   1. Prelude:
      1. Lipoproteins get stuck in vulnerable parts of blood vessel walls, leading to inflammation
      2. Macrophage infiltration, fibroblast proliferation, and continued development of fatty atheroma and fibrous cap
      3. Aspirin mostly* does not exert its effects here
   2. Climax:
      1. Chronic weakening of the fibrous cap extracellular matrix by infiltrating macrophages
      2. Rupture of the fibrous cap due to mechanical shear leads to exposure of the necrotic lipid core, attracting platelets
      3. Platelets and fibrin aggregate to form a thrombus, occluding the blood vessel
         1. ** Aspirin exerts its effects by inhibiting platelet activation and aggregation at this step
   3. For the average primary prophylaxis patient, more emphasis should be placed on controlling the progression of atherosclerosis > inhibiting platelets in the unlikely setting of plaque rupture
4. Q4: “What does the latest evidence on aspirin really show us?” 
   1. 1. Population: Adults aged >40 years with diabetes but no CVD,
      2. Parameters: RCT, 100mg aspirin versus placebo, followed for 7.4 years
      3. Outcomes: Aspirin group experienced a 1% ARR in CV events but 1% increased risk in major bleeding, translating to a negligible net benefit
   2. 1. Population: Men>55 years and women >60 years with average CV risk
      2. Parameters: RCT, 100mg aspirin versus placebo, followed for 5 years
      3. Outcomes: Similar low CV event rates between the aspirin (4.3%) and control group (4.5%)
         1.  
   3. 1. Population: Adults aged >70 years without CVD
         1. African Americans and Hispanic Patients → over > 65 years
      2. Parameters: RCT, 100mg aspirin versus placebo, followed for 5 years
      3. Outcomes: Similar low CV-related mortality rates between the aspirin (1%) and control group (1.2%)
         1. Caveat: 0.7% higher rate of all-cause mortality in the aspirin group compared to control group, driven largely by a paradoxically higher rate of colorectal cancer deaths
   4. 1. Includes all three trials discussed above as well as prior data
      2. Conclusion: Aspirin use is associated with a reduction in CV events with an OR of 0.90 (CI 0.85-0.95), and an increase in total major bleeding with an OR of 1.44 (CI 1.32-1.57).
         1. However, aspirin had no statistically significant impact on CVD-related mortality or all-cause mortality.
5. Q5: “How should we approach individualizing aspirin decision-making?”
   1. A seemingly easy way out →
      1. Helps synthesize and quantify data but is less generalizable than most clinicians realize
      2. Does not capture a variety of key risk factors: Smoker pack-year history? Family history of CVD? Obesity? Chronic inflammatory diseases? Coronary Calcium Score (CAC)?
   2. What are some particular risk factors that I should consider?
      1. Poorly controlled diabetes/metabolic syndrome
         1. Diving beyond the traditional measurements: A1c, Lipid Panel
         2. A high
      2. Lipoprotein (a) / Lp (a)
         1. Obtaining Lp (a) levels in presence of a positive family history of CVD is helpful for further risk stratification
      3. Coronary Calcium Score/ CAC
         1. Another helpful tool for stratification, especially for patients in intermediate risk categories
         2. 1. Population: Adults without CVD
            2. Parameters: Observational ,follow-up for 16 years for CVD incidence
            3. Outcomes: Identified a subgroup of aspirin-naive patients with CAC> 100 or > 400 who would have benefitted from aspirin when their ASCVD risk scores were pooled with CAC (NNT<NNH).
               1. For patients with CAC=0, aspirin demonstrated NNT>NNH.
   3. What are some reasons to continue or start  aspirin?
      1. Presence of (CAD, CVA, PAD)
      2. Presence of uncontrollable/refractory traditional risk factors (Ex. can’t quit heavy smoking, can’t control BP etc.)
      3. Presence of non-traditional or unmeasured risk factors not accounted for by traditional calculators
   4. Who should start aspirin is a slightly different conversation than who should continue aspirin
      1. Patients who are tolerating long term aspirin without bleeding complications are, on average, good candidates for continuing aspirin.
      2. For patients looking to start aspirin, the recent evidence shift in benefits/harms is more nuanced to balance and requires individualized risk assessment.
      3. Ultimately, know that the majority of patients will be OK regardless of the final decision on aspirin alone.
6. Summary: Shared decision-making on aspirin for primary prevention is much more nuanced than the ASCVD calculator can elaborate. Taking a robust history, understanding each patient’s risk tolerances, and utilizing new tools such as Lp (a) and CAC are all good ways to individualize this decision. However, proper management of known, modifiable risk factors remains the centerpiece of ASCVD prevention.

Contributors

Shreya Trivedi, MD, ACP Member – Editor, MOC Questions
Gregory Katz, MD – Host, Editor, MOC Questions
Cary Blum, MD – Host, Editor, MOC Questions
Yichi Zhang – Editor, MOC Questions

Reviewers

Marty Fried, MD, FACP
Kinjan Parikh, MD

Those named above, unless otherwise indicated, have no relevant financial relationships to disclose with ineligible companies whose primary business is producing, marketing, selling, re-selling, or distributing healthcare products used by or on patients.  All relevant relationships have been mitigated.

Release Date:  October 21, 2022

Expiration Date: October 21, 2025

CME Credit

This activity has been planned and implemented in accordance with the accreditation requirements and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint providership of the �ƹϵε�app and Core IM.  The �ƹϵε�app is accredited by the ACCME to provide continuing medical education for physicians.

The �ƹϵε�app designates this enduring material (podcast) for 0.50 AMA PRA Category 1 Credit™.  Physicians should claim only the credit commensurate with the extent of their participation in the activity.

ABIM Maintenance of Certification (MOC) Points

Successful completion of this CME activity, which includes participation in the evaluation component, enables the participant to earn up to 0.50 medical knowledge MOC Point in the American Board of Internal Medicine’s (ABIM) Maintenance of Certification (MOC) program.  Participants will earn MOC points equivalent to the amount of CME credits claimed for the activity. It is the CME activity provider’s responsibility to submit participant completion information to ACCME for the purpose of granting ABIM MOC credit.

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