Cookies on this website

We use cookies to ensure that we give you the best experience on our website. If you click 'Accept all cookies' we'll assume that you are happy to receive all cookies and you won't see this message again. If you click 'Reject all non-essential cookies' only necessary cookies providing core functionality such as security, network management, and accessibility will be enabled. Click 'Find out more' for information on how to change your cookie settings.

Lipid- and lipoprotein-modifying therapies have expanded substantially in the last 25 years, resulting in reduction in the incidence of major adverse cardiovascular events. However, no specific lipoprotein (a) Lp(a)]-targeting therapy has yet been shown to reduce cardiovascular disease risk. Many epidemiological and genetic studies have demonstrated that lipoprotein(a) is an important genetically-determined causal risk factor for coronary heart disease, aortic valve disease, stroke, heart failure and peripheral vascular disease. Accordingly, the need for specific lipoprotein(a)-lowering therapy has become a major public health priority. Approximately 20% of the global population (1.4 billion people) have elevated levels of Lp(a) associated with higher cardiovascular risk, though the threshold for determining 'high risk' is debated. Traditional lifestyle approaches to cardiovascular risk reduction are ineffective at lowering Lp(a). To address a lifelong risk factor unmodifiable by non-pharmacological means, Lp(a)-lowering therapy needs to be safe, highly effective, and tolerable for a patient population who will likely require several decades of treatment. N-acetylgalactosamine (GalNAc)-conjugated gene silencing therapeutics such as small interfering RNA (siRNA) and antisense oligonucleotide targeting LPA are ideally suited for this application, offering a highly tissue- and target transcript-specific approach with the potential for safe and durable lipoprotein(a) lowering with as few as three or four doses per year. In this review, we evaluate the causal role of lipoprotein(a) across the cardiovascular disease spectrum, examine the role of established lipid modifying therapies in lowering lipoprotein(a), and focus on the anticipated role for siRNA therapeutics in treating and preventing lipoprotein(a)-related disease.

Original publication




Journal article


Cardiovasc Res

Publication Date