Evaluating the Benefits of Aspirin in Lowering ASCVD Mortality for Elevated Lp(a) Individuals

Atherosclerotic cardiovascular disease (ASCVD) among young adults is a major public health challenge with a global prevalence of 7% to 30%. (1) Due to its antiplatelet properties, aspirin has long been known to be an effective treatment for ASCVD. For the purpose of primary prevention and lowering the events of premature ASCVD, it is necessary to identify individuals who would benefit from aspirin therapy more precisely. (2)

Premature ASCVD Demands Proactive Approach in India

There are significant differences between the ASCVD epidemiology in India and Western countries. It has been reported that more than 50% of coronary artery disease (CAD)-associated deaths in India occur before the age of 50 years, and 25% of myocardial infarctions (MIs) occur before the age of 40 years, which demands the early intervention of aggressive primary preventive measures to protect the young population from developing ASCVD events. (3)

Elevated Lipoprotein(a) – Strong Independent Risk Factor for ASCVD:

Elevated lipoprotein (a) [Lp(a)] is a strong independent risk factor for the development of ASCVD; approximately 1 in 5 ASCVD individuals have elevated Lp(a). (4) Additionally, there is a strong correlation between elevated Lp(a) in young Indians and the three characteristics of malignant CAD—high mortality, excessive prematurity, and extreme severity. (5)

The European Atherosclerotic Society (EAS) consensus statement has put forth an Lp(a) risk threshold as below-(6)

Reportedly, 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance and urging Lp(a) measurement as an essential part of all ASCVD management in Indians. (5)

Role of Aspirin as Primary Prevention in Elevated Lp(a)

It is hypothesised that, in light of the complex interactions between elevated Lp(a) and the effects of aspirin therapy, those with elevated Lp(a) would benefit more from low-dose aspirin therapy than the general population in terms of primary ASCVD prevention. In addition to its antiplatelet and antithrombotic properties, aspirin lowers Lp(a), particularly in patients with very elevated Lp(a), by inhibiting its production in the liver by suppressing apo(a) mRNA expression, independent of cyclooxygenase-1. (2)

Aspirin in Primary Prevention of ASCVD with Elevated Lp(a): Examining the Emerging Clinical Evidence

Aspirin Reduced Coronary Heart Disease (CHD) Events Among Individuals with Elevated Lp(a) in Primary Prevention: An observational study was conducted on a diverse population from 4 ethnicities (White, African American, Hispanic, and Asian) aged 45–84 years including 6632 participants from the Multi-Ethnic Study of Atherosclerosis (MESA). The participants had no identified cardiovascular disease, and 20% had elevated Lp(a) >50 mg/dL. The study showed a reduction in CHD events by 46% in participants using aspirin who had elevated levels of Lp(a) (HR 0.54, 95% CI, p = 0.03). This reduction was significant, and it was, in fact, noted that with aspirin use in participants with high Lp(a), the CHD event rates became similar in incidence to those with Lp(a) ≤50 mg/dL. (7)

Aspirin Benefits Young Patients with Elevated Lp(a)in Primary Prevention: Latest 2024 Study

A nationwide cohort study (n=2990) of US adults aged 40–70 years without clinical ASCVD assessed the association between regular aspirin use and ASCVD mortality among individuals with versus without elevated Lp(a) (≥50 versus <50 mg/dL) over a median 26-year follow-up. Regular aspirin use was associated with a 52% lower risk of ASCVD mortality among individuals with elevated Lp(a) (HR=0.48, 95% CI: 0.28–0.83. This study suggested that measurement of Lp(a) may help identify individuals who benefit from aspirin therapy for primary prevention. (4)

Aspirin in Primary Prevention: Guidelines Recommendations Promising Application When Appropriately Indicated

Statin Therapy and Combinations with Aspirin:

The Antithrombotic Trialist's (ATT) Collaboration estimated that statin therapy attenuates the risk of major vascular events in patients with aspirin. (11)In line with this data, a meta-analysis conducted on participants without ASCVD showed that background statin therapy reduces the absolute reduction in MI by at least one-third among participants treated with aspirin without changing bleeding risk. (12) Many investigations have evaluated the impact of statin treatment on Lp(a). Takagi and Umemoto conducted a meta-analysis of nine trials in which an atorvastatin arm was included, and they selected absolute follow-up levels as an effect measure. The findings indicated a significant, modest decrease of Lp(a) in the atorvastatin arms compared to the control groups. (13)

Key Takeaways:

• Atherosclerotic cardiovascular disease (ASCVD) among young adults is a public health challenge and is widely prevalent.
• One in five ASCVD patients has elevated lipoprotein(a) (Lp[a]), a potent independent risk factor for the development of ASCVD.
• Individuals with elevated Lp(a) benefit more from low-dose aspirin therapy than the general population for primary prevention of ASCVD.
• Aspirin reduced MACE (fatal coronary heart disease, nonfatal myocardial infarction, or fatal or nonfatal ischemic stroke) and ASCVD mortality.
• Statin therapy attenuates the risk of ASCVD (MI) by at least one-third in patients with aspirin; atorvastatin significantly reduces elevated Lp(a).

References:

Adapted from:

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