Emerging role of lipoprotein(a) lowering for CVD risk reduction
Pathophysiological, epidemiological and genetic studies provide strong evidence that lipoprotein(a) [Lp(a)] is a causal, independent risk factor for cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). [J Am Coll Cardiol 2017;69:692-711]
According to Professor Sotirios Tsimikas from the University of California San Diego, US, the estimated global population with elevated Lp(a) >50 mg/dL is 1.43 billion, and the associated risk is consistent across a broad spectrum of patients, including those with LDL-cholesterol <70 mg/dL. Hence, clinical guidelines now recommend considering Lp(a) screening and treatment for high-risk individuals, such as those with familial hypercholesterolaemia, or those with recurrent CVD despite optimal lipid lowering. [J Am Coll Cardiol 2018;71:177-192; Eur Heart J 2016;37:2999-3058]
Current therapies such as mipomersen and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors lower Lp(a) by 20–30 percent, but are not indicated for Lp(a) lowering as such. Emerging RNA-targeted therapeutics are the first to be specifically evaluated in randomized trials of Lp(a) lowering in individuals with high baseline Lp(a).
“Results are promising. For instance, the antisense oligonucleotide [ASO] IONIS-APO(a) produced dose-dependent reductions in Lp(a) levels of around 80 percent, with no apparent safety concerns,” reported Tsimikas. [Lancet 2016;388:2239-2253] Another ASO, AKCEA-APO(a), is now under phase I trial. [https://clinicaltrials.gov/ct2/show/NCT03070782]
“Specific therapies currently in clinical development will allow us to test the Lp(a) hypothesis that lowering elevated Lp(a) levels will lead to improved clinical outcomes,” he concluded.