The Lipoprotein(a) Drug Everyone Was Waiting For Is a Bust

One in five people has an elevated lipoprotein A, a genetically determined risk factor for earlier, more aggressive, atherosclerosis (artery plaque formation). Lp(a) is an extra protein that attaches itself to LDL and makes it more toxic.  More likely to find its way into plaque.  

I see patients with this condition in my office all the time. Lp(a) is an important enough risk factor that the latest cholesterol management guidelines (finally)  instruct physicians to check this number at least once in a patient’s lifetime.  

What has been frustrating about this risk factor is that, unlike for blood pressure and cholesterol, we’ve had no drugs that could meaningfully lower it. And unlike blood pressure and cholesterol, there are no lifestyle factors that impact Lp(a) either.  There’s simply no amount of marathons you can run or broccoli you can eat that will budge this number.  It just is. 

But a carrot has been dangling in front of us for a while.  Medications that have been shown to lower Lp(a) were a reality.  Pelacarsen, a new injectable drug that halts Lp(a) production at its source, was found to reduce Lp(a) levels dramatically.  It was developed by Novartis (the same company that brought us Ozempic and Wegovy), so the hopes were high that we finally had a magic bullet.  

But there’s a difference between making a number look good and improving health (sound familiar?).  And what we really needed to know was whether lowering Lp(a) impacted outcomes.  That takes a randomized, controlled clinical trial and long follow-up.  And the long follow-up, unfortunately, was truly disappointing.  

What Did This New Trial Actually Find?

In a trial of more than 8,300 people with high Lp(a) and existing heart disease Pelacarsen did indeed substantially lower Lp(a) levels. It did not, however, lower their risk of heart attack, stroke, cardiovascular death, or needing an urgent heart procedure, compared to placebo - the outcome that really matters. 

This wasn't a poorly run trial looking for an excuse to fail. Patients in both groups already had their LDL cholesterol well controlled with other medications, so this was a clean test of one specific question: does lowering Lp(a) itself, on top of everything else already being done right, add any additional protection? The answer, at least with this drug, was a resounding no.

A clear demonstration that lowering a marker and lowering risk are not automatically the same thing, and that not every biologically plausible target turns out to be a treatable one.

So What Should You Do If Your Lp(a) Is High?

Nothing has changed. Lp(a) is still genetic, still not moved by diet or exercise, and now, still without an approved medication that lowers it directly. If you've had it checked and it came back high (like it was for me), that reality hasn't shifted because one drug fell short. What has always mattered, and still matters just as much today, is what you do about the other side of that equation.

The way we’ve been getting around this genetic risk marker for some time is to just lower LDL.  The thinking being that if LDL is more toxic because it has Lp(a) attached to it - and we can’t do anything about the Lp(a) - at least we can lower the number of toxic LDL particles.  Not perfect, but a reasonable approach.  So we do have a partial solution.

And you should not give up on the promise of Lp(a) lowering just yet.  There are lots of other companies chasing the same goal.  Whether it was Pelacarsen itself that introduced confounding factors that impacted risk in other, unclear ways - or whether lowering Lp(a) is a truly futile pursuit is not yet settled.  More trial results will be needed.

How Step One Foods Can Help

Food can do real work and make a real difference here. Step One Foods help lower LDL through soluble fiber, plant sterols, antioxidants, and unsaturated fats. Those are different, complementary mechanisms to statins.  If your Lp(a) is elevated, getting your LDL as low as realistically possible isn't a nice-to-have. It's the whole strategy, and food is one lever that's fully in your control.  

Plus - remember that even without dramatic LDL reductions, what you eat matters.  Just adding 10 grams of fiber (what’s in two servings of Step One Foods) lowers your risk of experiencing a cardiovascular event by 14%, and reduces your risk of dying from heart disease by 27%.  That’s not a lower lab number. That’s an outcome.

Important Context

Lp(a) is a risk factor.  It’s not a disease guarantee.  We always have to look at the whole patient and evaluate the totality of their risk. In someone without known heart disease, I frequently turn to coronary calcium scanning to help me decide how aggressive I need to be in terms of prevention efforts.  A 0 calcium score is still a highly favorable outcome with the same prognostic power regardless of your Lp(a) level.  My calcium score has been 0 over multiple tests now, so I’m thinking of my Lp(a) level as a yellow light, not a red one for now.

And we have lots of medication options for lowering LDL if the calcium score does not come back with a favorable score.  That’s why the medications are there.  And medications truly are not bad.  They’re just not the complete answer.

Because health is more than a number.