Interesting thread of comments, I would like to make some clarifications, as I see a lot of close but inaccurate numbers being thrown out on the internet. Now that Lp(a) is getting traction clinically, there is a lot of quoting data that is not entirely correct.
1- PCSK9 inhibitors lower Lp(a) 20-30%, but in patients with high Lp(a) (>50 mg/dL), the effect is only 14%. This is the number that should be quoted in this context. See specific paper on this. ncbi.nlm.nih.gov/pubmed/30561610
2- ASOs lower Lp(a) >99% depending on the dose. In the phase 3 trial about to start the dose is 80 mg monthly and the mean Lp(a) reduction is expected to be 80% based on phase 2 data. That means some will get 70% reduction and some 90% reduction. No need to get everyone to zero
3- The number of subjects estimated to have Lp(a) >50 mg/dL is 1.4 billion. This is ~125 nmol/L, not 60-70 nmol/L as I saw a discussion on this by experts. 60-70 nmol/L is in normal range and ~25-30 mg/dL. 870https://www.ncbi.nlm.nih.gov/pubmed/29325642
4- There are potentially hundreds of LPA snps associated with Lp(a) levels. Most vary be race and can go in opposite directions according to race, so dont help you clinically, but can be of academic interest. See my prior tweet on this with rs3798220.
5- Most LPA snps are also non-functional, and often merely reflect the presence of small isoforms, so by themselves cause no harm. In the Ionis studies, only 2/3rds of subjects with elevated Lp(a) had a known snp, but almost all subjects had at least one small isoform.
6- Most data suggests it the Lp(a) level that meditates risk and if one adjusts for LPA snps and isoforms, they fall out as being significant. This makes life simple, just measure Lp(a). If interested in LPA generics, then snps and isoforms are of interest.
7- what to do when you find high Lp(a) is evolving. First measuring Lp(a) can reclassify about 4/10 (40%) subjects in intermediate risk, to higher or lower risk than can be gleaned from typical assessments. ncbi.nlm.nih.gov/pubmed/25169167
These subjects now in higher risk need full court press on all preventative measures. If recurrent events despite optimal Rx, consider apheresis. Ty PCSK9i or niacin, both unapproved and untested for this indication. Or hold on until the Ionis/Novartis trial reads out in 2024.
What clinicians and patients are witnessing now is the active evolution of a new awareness of a risk factor, when the head is taken out of the sand. There this quite a bit of new angst of knowing a risk factor exists but having a suboptimal therapy for it.
In some ways, its daunting to be part of a historic time in the development of a new therapy for an unmet need that affects so many people. All therapies have had to go through this, and trials need to be done before approval, and hopefully it will end well with a positive trial
