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Who should we start on aspirin for primary prevention of cardiovascular disease?!
Transcript
Who should we start on aspirin for the primary prevention of cardiovascular disease? Primary prevention means we’re talking about someone who’s never had a heart attack or stroke. The USPSTF guidelines stated with moderate certainty that there is a small net benefit of daily aspirin in patients aged 40 to 59 with a 10 year CBD risk of 10 percent or more.
In patients over 60, the USPSTF says don’t prescribe, as there’s moderate to high evidence that daily aspirin has no net benefit, or that the harms outweigh the benefit. So, patients aged 40 to 59 with a 10 year CVD risk of 10 percent or more should be selectively prescribed daily aspirin based on physician judgment and patient preferences.
We need to be engaging in shared clinical decision making here. To hear more, check out the Core IM Mind the Gap episode, Aspirin for Primary Prevention.
And here I review, link to, and excerpt from CoreIM‘s Aspirin for Primary Prevention: Mind the Gap Segment
Posted: October 19, 2022
By: Dr. Greg Katz, Dr. Cary Blum, Dr. Yichi Zhang and Dr. Shreya P. Trivedi
Graphic: Lizzie Holland
Audio: Yichi Zhang
Peer Review: Dr. Kinjan ParikhPodcast: Play in new window | Download
Time Stamps
- 02:53 Guideline recommendations
- 07:00 How does Aspirin work?
- 09:11 Trial Data
- 13:00 ASCVD Risk Calculator
- 18:07 Starting vs. Stopping Aspirin
- 22:11 Summary
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Show Notes
Q1: “Have you been getting questions about aspirin?”
- Patients are hearing about aspirin from a variety of sources differing drastically in credibility: USPSTF? The NY Times? Friends and family?
- As clinicians practicing evidence-based medicine, what is our best approach to educating patients about aspirin?
Q2: “What do the guidelines say about aspirin’s role in primary prevention?”
- ACC/AHA guidelines (2019):
- For patients aged 40-70 years, aspirin should be used infrequently for primary prevention [Class IIb recommendation]
- For patients aged >70 years, the evidence does not support the use of aspirin for routine primary prevention [Class III recommendation]
- USPSTF guidelines:
- 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)
- For patients aged >60 years: do not initiate aspirin for primary prophylaxis (grade D)
Q3: “Why and how does aspirin work?”
- Prelude: Atherosclerotic Progression
- Lipoproteins get stuck in vulnerable parts of blood vessel walls, leading to inflammation
- Macrophage infiltration, fibroblast proliferation, and continued development of fatty atheroma and fibrous cap
- Aspirin mostly* does not exert its effects here
- Climax: Plaque Rupture
- Chronic weakening of the fibrous cap extracellular matrix by infiltrating macrophages
- Rupture of the fibrous cap due to mechanical shear leads to exposure of the necrotic lipid core, attracting platelets
- Platelets and fibrin aggregate to form a thrombus, occluding the blood vessel
- ** Aspirin exerts its effects by inhibiting platelet activation and aggregation at this step
- 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
Q4: “What does the latest evidence on aspirin really show us?”
- ASCEND Trial (2018)
- Population: Adults aged >40 years with diabetes but not CVD
- Parameters: RCT, 100mg aspirin versus placebo, followed for 7.4 years
- Outcomes: Aspirin group experienced a 1% ARR in CV events but 1% increased risk in major bleeding, translating to a negligible net benefit
- ARRIVE (2018)
- Population: Men>55 years and women >60 years with average CV risk
- Parameters: RCT, 100mg aspirin versus placebo, followed for 5 years
- Outcomes: Similar low CV event rates between the aspirin (4.3%) and control group (4.5%)
- ASPREE (2018)
- Population: Adults aged >70 years without CVD
- African Americans and Hispanic Patients → over > 65 years
- Parameters: RCT, 100mg aspirin versus placebo, followed for 5 years
- Outcomes: Similar low CV-related mortality rates between the aspirin (1%) and control group (1.2%)
- 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
- USPSTF Meta-Analysis (2022)
- Includes all three trials discussed above as well as prior data
- 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).
- However, aspirin had no statistically significant impact on CVD-related mortality or all-cause mortality.
Q5: “How should we approach individualizing aspirin decision-making?”
- A seemingly easy way out → 10-year ASCVD Risk Calculator
- Helps synthesize and quantify data but is less generalizable than most clinicians realize
- 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)?
- What are some particular risk factors that I should consider?
- Poorly controlled diabetes/metabolic syndrome
- Diving beyond the traditional measurements: A1c, Lipid Panel
- A high TG to HDL ratio is indicative of insulin resistance
- Lipoprotein (a) / Lp (a)
- Obtaining Lp (a) levels in presence of a positive family history of CVD is helpful for further risk stratification
- Many patients with family hypercholesterolemia are found to have higher levels of Lp (a)
- A higher Lp (a) level is an independent and causal risk factor for CVD
- Coronary Calcium Score/ CAC
- Another helpful tool for stratification, especially for patients in intermediate risk categories
- MESA Study (2021)
- Population: Adults without CVD
- Parameters: Observational ,follow-up for 16 years for CVD incidence
- 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).
- For patients with CAC=0, aspirin demonstrated NNT>NNH.
- What are some reasons to continue or start aspirin?
- Presence of secondary prevention indications (CAD, CVA, PAD)
- Presence of uncontrollable/refractory traditional risk factors (Ex. can’t quit heavy smoking, can’t control BP etc.)
- Presence of non-traditional or unmeasured risk factors not accounted for by traditional calculators
- Who should start aspirin is a slightly different conversation than who should continue aspirin
- Patients who are tolerating long term aspirin without bleeding complications are, on average, good candidates for continuing aspirin.
- For patients looking to start aspirin, the recent evidence shift in benefits/harms is more nuanced to balance and requires individualized risk assessment.
- Ultimately, know that the majority of patients will be OK regardless of the final decision on aspirin alone.
- 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.
