Dr. Gurleen Kaur

DocwireNews

Elevated lipoprotein(a) [Lp(a)] is an established risk factor for atherosclerotic cardiovascular disease (ASCVD), which has been demonstrated in several epidemiological, genome-wide association, and Mendelian randomization studies.1-3 However, no available therapies that lead to a substantial reduction in Lp(a) exist, and no clinical trial data support that lowering Lp(a) reduces adverse cardiovascular events.
Dr. Ron Blankstein discussed the Lp(a) therapeutics currently in development at the recent American Society of Preventive Cardiology 2023 Congress on CVD Prevention.
Novel Lp(a)-lowering therapies target apolipoprotein(a) [apo(a)], a key component of Lp(a). Several therapies are currently in various phases of clinical trials. Pelacarsen, a ligand-conjugated antisense oligonucleotide that binds to messenger RNA (mRNA), subsequently causing mRNA degradation and blocking the production of the apo(a) protein, has demonstrated the ability to reduce Lp(a) levels in a dose-dependent manner in patients with established cardiovascular disease.4 At the highest cumulative dose of pelacarsen (20 mg weekly), there was a mean 80% reduction in Lp(a).4 Pelacarsen 80 mg given subcutaneously monthly is currently being investigated in a phase 3 outcomes trial, HORIZON (NCT04023552), which recently completed enrollment of approximately 8300 patients.
Another therapeutic option for lowering Lp(a), olpasiran, is a small interfering RNA (siRNA) that leads to the degradation of the apo(a) mRNA, thereby preventing protein translation. The ability of olpasiran to significantly reduce Lp(a) concentrations in patients with established ASCVD was recently shown in the OCEAN(a)-DOSE trial.5 A Lp(a) reduction of more than 95% was seen when the drug was administered every 12 weeks at a 75-mg or 225-mg dose.5 Olpasiran subcutaneously every 12 weeks is being investigated in a phase 3 clinical trial, OCEAN(a)-Outcomes. Enrollment for that trial began in December 2022 (NCT05581303).
Dr. Blankstein called attention to the notable differences in the design of the 2 phase 3 clinical trials investigating Lp(a)-lowering therapies, HORIZON and OCEAN(a)-Outcomes. To be included in the HORIZON trial, patients needed an Lp(a) ≥70 mg/dL, while the threshold for enrollment in the OCEAN(a)-Outcomes trial is Lp(a) &gt;200 nmol/L. Both trials include a secondary prevention population. HORIZON defines prior cardiovascular disease as myocardial infarction (MI), ischemic stroke, or symptomatic peripheral arterial disease, while OCEAN(a)-Outcomes is including patients with either MI or coronary revascularization with percutaneous coronary intervention and at least 1 additional risk factor. The primary end point of both trials is cardiovascular death, MI, and urgent coronary revascularization. The HORIZAN trial&#8217;s primary end point also includes nonfatal stroke.
The results of these trials are eagerly awaited, as they will provide important insight into whether lowering Lp(a) improves cardiovascular outcomes.
A few additional compounds are also currently in the early stages of development, including the siRNA compounds zerlasiran, also known as SLN360 (NCT05537571), and LY3819469 (NCT04914546), as well as the oral Lp(a) inhibitor muvalapin (NCT04472676).
Dr. Gurleen Kaur is a resident at Brigham and Women’s Hospital and served as a CardioNerds Conference Scholar during the American Society of Preventive Cardiology 2023 Congress on CVD Prevention. 
References
<ol>
<li>Erqou S, Kaptoge S, Perry PL, et al; Emerging Risk Factors Collaboration. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412-423. doi:10.1001/jama.2009.1063</li>
<li>Kamstrup PR, Tybjærg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol. 2013;61(11):1146-1156. doi:10.1016/j.jacc.2012.12.023</li>
<li>Clarke R, Peden JF, Hopewell JC et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518-2528. doi:10.1056/NEJMoa0902604</li>
<li>Tsimikas S, Karwatowska-Projopczuk E, Gouni-Berthold I, et al. Lipoprotein(a) reduction in persons with cardiovascular disease. N Eng J Med. 2020;382:244-255. doi:10.1056/NEJMoa1905239</li>
<li>O’Donoghue M, Rosenson R, Gencer B, et al. Small interfering RNA to reduce lipoprotein(a) in cardiovascular disease. N Eng J Med. 2022;387:1855-1864. doi:10.1056/NEJMoa2211023</li>
</ol>

Laura Litwin

Study Evaluates New Criteria From Asian Working Group for Cachexia in Patients With Lung Cancer

Lung Cancer

Patrick Daly

Comparing Azacitidine, Immune Checkpoint Inhibitor Regimens in MDS

ASH 2024

Cecilia Brown

What Patients With NSCLC Say About Treatment-Related Toxicities, Therapeutic Drug Monitoring

Non-Small Cell Lung Cancer

Latest News

Lp(a) Therapeutics: A New Addition to the Armamentarium for ASCVD?

Cardionerds is an entertaining and educational medical cardiology podcast created by three cardiologists. They want to bring high yield cardiovascular concepts in a fun and engaging format for their listeners of all levels. Click below to learn more!

CardioNerds

Elevated lipoprotein(a) is an established risk factor for atherosclerotic cardiovascular disease.

About Us

Editorial Policy

Advertising

eNewsletters

Contribute

Contact Us

MashupMD

Blood Cancers Today

Cancer Nursing Today

GU Oncology Now

Urban Health Today

Bile Duct Cancer

Colorectal Cancer

Gastroesophageal Cancer

Gastric Cancer

GEP-NETs

GIST

Liver Cancer

Pancreatic Cancer

GI Oncology Now

Anemia

Deep Vein Thrombosis

Essential Thrombocythemia

Hemophilia

Immune Thrombocytopenic Purpura

Myelodysplastic Syndromes

Myelofibrosis

Myeloproliferative Neoplasms

Polycythemia Vera

Pulmonary Embolism

Sickle Cell Disease

Thrombocytopenia

Thrombophilia

Thrombosis

Thrombotic Thrombocytopenic Purpura

Venous Thromboembolism

von Willebrand Disease

Heme Today

Acute Kidney Injury

ADPKD

Anemia and Kidney Disease

Chronic Kidney Disease

COVID-19 and Kidney Disease

Diabetes and Hypertension

End-Stage Renal Disease

Gout

Hyperkalemia

IgAN

Kidney Transplantation

Metabolic Acidosis

Nephrology Times

Mesothelioma

Small Cell Lung Cancer

Squamous Cell Lung Carcinoma

Lung Cancers Today

Atherosclerotic Disease

Atrial Fibrillation

Heart Failure

Hypertension

Interventional Cardiology

Lipid Management

Practice Tips With Dr. Lichaa

Preventive Cardiology

Stroke

Cardiology

Breast Cancer

Gynecologic Cancer

Head and Neck Cancer

Skin Cancer

Oncology

Sleep

Urology

Diabetes

Ophthalmology

— Demodex Blepharitis

Neurology

Rheumatology

Gastroenterology

Pulmonology

Infectious Diseases

— HIV

Health and Wellness

Lupus

Future of Medicine

Orthopedics

Pharmacology

Career News

More

Conferences

The Sleep Source With Dr. Morse

The Oncology Brothers

Rheumatology Rounds With Dr. Maheswaranathan

Healthcare Unfiltered

The Fellow on Call

Partners

Hurricanes & Health Care

Career Center

Expert Interviews

Subscribe