Lipoprotein(a) Reduction in Persons with Cardiovascular Disease

Polygenic modulation of lipoprotein(a)-associated cardiovascular risk

“…However, the optimal management of patients with elevated lipoprotein(a) is uncertain. Antisense inhibitors that potently lower lipoprotein(a) are currently being studied in clinical trials in subjects with elevated lipoprotein(a) and established cardiovascular disease [17][18][19] .…”

“…Although elevated lipoprotein(a) is associated with increased cardiovascular risk, the optimal treatment of elevated lipoprotein(a) is uncertain. While there are currently no approved therapies for lowering lipoprotein(a), antisense oligonucleotides that target apolipoprotein(a) and reduce lipoprotein(a) levels by up to 80% have been developed and are currently being studied in clinical trials [17][18][19] . At the individual level, there is substantial variability in cardiovascular risk among individuals with elevated lipoprotein(a) 1,20,21 , and it remains unclear whether isolated elevated lipoprotein(a) in the absence of other cardiovascular risk factors merits treatment to reduce cardiovascular risk .…”

The dedicated “Lp(a) clinic”: A concept whose time has arrived?

“…In ODYSSEY OUTCOMES, a 1 mg/dL reduction in Lp(a) with alirocumab was associated with a hazard ratio of 0.994. If this is extrapolated to more potent reductions than can be obtained with antisense oligonucleotides, as shown recently with AKCEA-APO (a)-L Rx (now named TQJ230 dosed at 80 mg monthly) with a mean 80 mg/dL reduction in Lp(a) [15], it would imply that a significant benefit may be present.…”

“…A randomized trial is now underway to test apheresis compared to apheresis in apheresis eligible patients (MultiSELECt trial) [12]. The emerging clinical development of potent Lp(a)-lowering drugs that completed phase 2 trials [13][14][15], and now entering phase 3 (HORIZONS trial, https://clinicaltrials.gov/ct2/show/NCT04023552), will allow testing of the "Lp(a) hypothesis", namely that reducing elevated Lp(a) levels leads to a marked clinical benefit.…”

“…The rationale for a dedicated "Lp(a) Clinic" can be provided by the following concepts: 1-the confluence of diverse levels of evidence that Lp(a) is a causal risk factor for CVD; 2-the high prevalence of elevated Lp(a) [16]; 3-the significant under-diagnosis of patients at risk [16]; 4the heterogeneity of clinical manifestations, ranging from stroke in pediatric age groups, to myocardial infarction in young adults, to elderly individuals with CAVD, 5-the need to centralize clinical care based on common pathophysiological commonalities across clinical phenotypes rather than in fragmented traditional clinical departments; 6-the presence of familial clustering that offers opportunities for cascade screening to enhance early diagnosis and care [17,18]; 7-the enhancement of awareness of elevated Lp(a) for patients and referring physicians; 8-the underappreciation that in patients with elevated Lp (a) the true "LDL-C" is lower than appreciated, since a significant portion of plasma cholesterol is carried by and present on Lp(a) particles [19]; 9-the advancement of novel Lp(a) lowering approaches, such as RNA therapeutics [13][14][15], allowing for enhanced education and participation in clinical trials of patients and physicians and 10-the potential to improved clinical outcomes. Some of the salient issues above are discussed in more detail below.…”