More Than 5 Million US Adults Could Benefit From Lp(a)-Targeted Therapies

As a new class of lipoprotein(a) [Lp(a)]-lowering therapies approaches pivotal phase 3 readouts, new research highlights the potential public health impact: more than 5.3 million US adults with atherosclerotic cardiovascular disease (ASCVD) and elevated Lp(a) could be eligible for these emerging treatments, with the possibility of preventing tens of thousands of recurrent cardiovascular events every year.¹

The findings were presented at the 2026 American College of Cardiology (ACC.26) Scientific Session.

The Scale of Residual Risk

Lp(a) has emerged as one of the most important independent, causally validated cardiovascular risk factors that current standard-of-care therapies cannot adequately address.² Unlike low-density lipoprotein cholesterol (LDL-C), Lp(a) levels are primarily genetically determined and remain largely unresponsive to statins, PCSK9 inhibitors, or ezetimibe, therapies that form the backbone of ASCVD secondary prevention. As a result, millions of patients remain at elevated risk despite optimal lipid-lowering treatment. The urgency of addressing this gap has been underscored by the 2026 ACC/AHA Dyslipidemia Guideline, which now recommends measuring Lp(a) at least once in a patient's lifetime to identify those at higher ASCVD risk.³

The study used data from the National Health and Nutrition Examination Survey (NHANES) 1988–1991, the only NHANES cycle in which Lp(a) was directly measured, to identify US adults with ASCVD and Lp(a) levels at or above 70 mg/dL, the threshold used in major phase 3 trials of emerging Lp(a)-lowering agents.¹ The sample was reweighted using inverse probability weighting to align ASCVD prevalence and demographics with the contemporary NHANES 2021–2023, generating a nationally projected eligible population. A published secondary prevention risk score incorporating Lp(a) values was then applied to estimate baseline 5-year ASCVD event rates and model the preventable events under varying levels of relative risk reduction (RRR).

The projected eligible population was approximately 5.3 million US adults, 57% female, with a mean age of 63.6 years, mean Lp(a) of 103.2 mg/dL, and mean LDL-C of 159.1 mg/dL. Their estimated mean 5-year risk of recurrent ASCVD events was 23.2%, corresponding to 1.2 million expected events in the absence of Lp(a)-targeted therapy.

Modeling across 4 treatment scenarios demonstrated meaningful event prevention at each efficacy threshold. Achieving 10%, 15%, 20%, 25%, and 30% RRR could potentially prevent approximately 123,000, 184,000, 245,000, 307,000, and 368,000 recurrent ASCVD events over 5 years, respectively—equivalent to roughly 25,000 to 74,000 prevented events per year.

The Urgency of Screening

The findings arrive alongside growing recognition that Lp(a) testing remains chronically underused in clinical practice. Lp(a) is both proatherogenic and prothrombotic, yet many patients with normal LDL panels carry subclinical Lp(a) burdens that go undetected for decades.⁴ Individuals can harbor significantly elevated Lp(a) while appearing low-risk on conventional lipid panels, a gap that population-level screening could close. Family-based screening may be particularly efficient given the strong heritability of Lp(a) expression, which is stable from early adulthood onward.

However, the authors acknowledged several study limitations.¹ NHANES data may carry participation bias, and peripheral artery disease prevalence was imputed using an established model rather than directly measured. As with all modeling studies, results represent projected estimates rather than observed outcomes. The magnitude of benefit will ultimately depend on the RRR demonstrated in ongoing cardiovascular outcomes trials, findings from which are anticipated to reshape clinical guidelines and prescribing practice.

Despite these limitations, the analysis offers a population-level framework for anticipating the cardiovascular burden that Lp(a)-targeted therapies could alleviate in the US. With phase 3 data from studies on Lp(a)s pelacarsen (TQJ230; Novartis) and olpasiran (Amgen) expected in the near term, quantifying the eligible population and projecting preventable events is a timely and policy-relevant contribution. If these therapies deliver even modest RRR in outcomes trials, the public health dividend could be substantial.

References

1. Wong ND, Karthikeyan H, Fan W, et al. Estimated preventable cardiovascular disease events from lipoprotein(a)-targeted therapy. Presented at: ACC.26; March 28-30, 2026; New Orleans, LA.

2. Hippensteele A. NLA 2025: novel therapeutic approaches show promise for targeted reduction of Lp(a) in patients with ASCVD. Pharmacy Times^®. May 31, 2025. Accessed May 14, 2026. https://www.pharmacytimes.com/view/nla-2025-novel-therapeutic-approaches-show-promise-for-targeted-reduction-of-lp-a-in-patients-with-ascvd

3. Wiggins BS, Barac A, Benzinger CP, et al. 2026 dyslipidemia guideline-at-a-glance. J Am Coll Cardiol. March 18, 2026. Accessed May 14, 2026. https://www.jacc.org/doi/10.1016/j.jacc.2026.02.4872

4. Green L. Understanding elevated lipoprotein(a): a focus on cardiovascular risk and screening recommendations. AJMC^®. March 8, 2024. Accessed May 14, 2026. https://www.ajmc.com/view/understanding-elevated-lipoprotein-a-a-focus-on-cardiovascular-risk-and-screening-recommendations