Cardiovascular Health 2025

#1083

New Pill From Merck Could Slash Cholesterol Levels, Trials Show

The drug targets the PCSK9 protein, and could give millions of people a more affordable option to reduce their heart disease risk.

Merck, the company that introduced statins to the world nearly 40 years ago, has a new, intensely powerful pill that can slash levels of dangerous LDL cholesterol to levels almost never seen in adults.

The new pill, enlicitide, blocks a liver protein, PCSK9, that slows the body’s ability to clear cholesterol. With most PCSK9 blocked, LDL levels plummet and rates of heart attacks and strokes in high risk patients fall by up to 20 percent in just the first year.

At least six million adults in the United States are eligible for drugs that block PCSK 9.

Merck’s head of research said the goal is to make the pill affordable. It would be an alternative to expensive biweekly or monthly injections of monoclonal antibodies that do the same thing. But only around one percent of eligible patients take the injections, which include Praluent by Regeneron and Sanofi, and Repatha by Amgen. Many patients don’t want to inject themselves, and insurers put up obstacles to paying, cardiologists say. The drugs’ list prices are more than $500 a month.

Multiple studies over the years have shown that the lower the LDL level, the better — heart attack and stroke rates drop as LDL levels fall. And there appears to be no downside to having an astonishingly low LDL level, including one in the teens or twenties. Adults who are not taking cholesterol-lowering drugs usually have levels above 100.).

“Lower is better for sure,” said Dr. Daniel Soffer, a cardiologist at the University of Pennsylvania.

Read the full story: New Pill From Merck Could Slash Cholesterol Levels, Trials Show (NYT)

7 Likes
Enlicitide (new oral PCKS9 inhibitor), way easier to take than previous gens of them
To rapamycin or not to rapamycin — that’s the question
#1084

At this point I go all out

high dose statin/ezetimibe/bempedoic acid/psyllium husk, and a wealth of other supplements to crush that ldl below 30

I wish the psk9 inhibitors were cost affective than I’d have the full arsenal

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#1085

You’d expect that to drive down the cost of existing medicines, especially repatha in this case. You’d be sorely mistaken!

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#1086

It’s going to be interesting to see the pricing (and prescription requirements… do you need to “fail” on a cheaper statin before they’ll pay for a PCSK9 Pill?).

In theory the market for pills is much, much larger than the injections (people hate injections, generally) and they have refrigeration requirements. So the price can be much lower and still generate vast revenues… we’ll see.

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#1087

Whatever. I’ll just wait for those pills to become available in India, one way or another. India has a truly epic size problem with CVD. The government will make it a top priority to get ahold of these meds by hook or by crook, patents be damned. And when they become available, I’m placing my order. I have zero faith in the insurance industry in the US, their willingness to cover them unless you’re on the verge of death if not actually clinically expired, or the pharma companies and PMBs marketing them at anything less than the price of your first born. I have no desire to deal with obstinate doctors, ghoulish companies and other bloodsuckers along the chain. Order from India, done. First however let’s wait until the drugs actually come out and then hit India. Then we’ll talk. YMMV.

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#1088

I actually disagree. I think the fat jabs show that people aren’t as resistant as you think. Repatha and Praluent are both simple “click pens” which you can do at home.

I think the problem is simply the cost. Antibodies generally cost a lot more to manufacture, since they need to be made by living cells, then purified etc. It’s a big industrial process. By comparison, small molecules can be made by mixing ingredients in the lab.

Still, the overall biggest factor is that price gouging in the US healthcare system, because a Repatha injection might cost $150 in other parts of the world. Not “cheap” but nowhere near as pricey as in the US.

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#1089

Cronos, I just learned from you that CVD is a particularly bad problem. Do you know what this is attributed to? They don’t eat much cow, but of course they are consuming dairy and other animals. This fact only just leads me to guess their issue is not due to consuming more sat fat, but?

And ARGH on US health insurance. @relaxedmeatball I qualify for repatha and got the pre authorization blah blah blah…. But alas, it’s still subject to my 8k deductible, so I pay for it. Fortunately, repatha offers coupons. For years, it only cost $5 a month, but a couple years ago they started to cap it to a 3k coupon benefit max per year. Still nice, but it doesn’t make me any less bitter :slight_smile:

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#1090

As popular as the injections are now, I think you’ll see how many people have been holding out for a pill once orforglipron (small molecule GLP-1 agonist, no food/water restrictions for absorption) hits the market next year. Eli Lilly already has manufactured literally billions of tablets in preparation for its release, and they pretty much know what they’re doing.

1 Like
#1091

There was a great Attia podcast about India and CVD/insulin resistance (with a doctor of Indian origin). #69 - Ronesh Sinha, M.D.: Insights into the manifestation of metabolic disease in a patient population predisposed to metabolic syndrome, and what it teaches us more broadly - Peter Attia

From what I remember (years since I listened), the guest stated that Indian origin people tend to accumulate a lot of visceral fat, tend to not have much muscle mass, and aren’t particularly “athletic” in general. (Side note: consider Indian athletes, Olympic Games performance etc). He posits that they simply don’t handle high calorie diets very well, and they store lots of fat around organs, lots of fat inside muscle tissue etc. So basically they get insulin resistant and get lots of inflammation very easily.

Attia starts the podcast by talking about a patient of his (South Asian) who had insulin resistance that the usual approaches weren’t fixing.

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#1092

@relaxedmeatball has it. There is a genetic component in the South Asians that predisposes to the TOFI phenotype (Thin Ouside Fat Inside), so already at a BMI of 21 you can have metabolic derangements leading to diabetes and CVD. The diet is problematic, because it’s pretty far from traditional these days, calories are much higher and a ton of regional cuisines have unhealthy components like high levels of SFA, and in the urban setting fried food, fast food and processed foods and sodas. And many urban Indians don’t exercise much or do anything near enough to burn all those excess calories.

The result is a diabetes and CVD epidemic. And while incidence matters, it’s the absolute numbers that are the problem - India has recently overtaken China as the most populous country on earth. There are now tens of millions who are at risk of CVD or already suffering from it. And it’s getting worse, with childhood obesity rising rapidly, setting up a huge challenge for generations to come. Education and lifestyle changes are always going to be a hard path. You’re going to have to add a pharmaceutical component to tackle this, and it has to be affordable for the population. So they’ll follow their playbook when it comes to CVD and diabetes drugs, and scour the world for the most effective drugs that can be easily replicated and either strike a deal with the original manufacturer/marketer, or make a knockoff for the domestic market. That if course is greatly facilitated by a giant pharma industry where generics are made and where a huge amount is also produced as subcontractors for Western pharma companies. That’s where we come in, placing our orders. CVD is not an exotic collection of pathologies, so odds that a drug that’s proven to be safe and effective will eventually appear in India is high, and it should be relatively affordable. We’ll see.

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#1093

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#1094

I don’t know. I use repatha every two weeks with the Sureclick pen and it hurts like a MF. I am no stranger to all sorts of injections, and that one I always dread. Its a pretty big volume and a fast flow, so that doesn’t help.

#1095

Any idea if Dayspring also has high Lp(a)?

#1096

@Rapasailor my doc just switched me to a regular ‘manual’ syringe for repatha. LIFE CHANGING!!!

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#1097

That’s a great idea! I’m going to request that next time as well. That stupid pen hurts every time.

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#1098

Yessss, I can’t believe I’ve been using that godforsaken click pen for years!!

It didn’t hurt me very often, but O.M.G… when it did, it was torture!! It takes soooo long and you just want to pull it out, but it’s so expensive you have to just sit there and take it!!!

This still hurts a touch, but because you can control it, you can simply give yourself a break before finishing.

#1099

As promised I’m posting results of the n=1 experiment wrt. lipid medication. No changes in diet or exercise or other lifestyle factors, sleep, level of stress insofar as I can tell (low), supplements. The only med change has been the addition of 80mg/day of telmisartan for two weeks (first 20mg/day for 4 weeks, followed by 4 weeks of 40mg/day, before the final 2 weeks of 80mg/day that I have continued on with to this day). This test (4) keeps pitavastatin 4mg/day but adds a combined pill Brillo EZ of 180mg/day + 10mg/day ezetimibe.

So the tests are as follows - each intervention roughly 6 weeks with no washout period:

(1)pitavastatin 4mg/day alone (switched from atorvastatin 10mg/day)

(2)pitavastatin 4mg/day + bempedoic acid 180mg/day

(3)pitavastatin 4mg/day + ezetimibe 10mg/day

(4)pitavastatin 4mg/day + bempedoic acid 180mg/day + ezetimibe 10mg/day - CURRENT TEST ON 10/28/25.

This test (4) has been of a drug regimen that has been ongoing since the initiation on 08/09/25.

Pitavastatin 4mg/day alone vs pitavastatin 4mg/day + bempedoic acid 180mg/day vs pitavastatin 4mg/day + ezetimibe 10mg/day vs pitavastatin 4mg/day + bempedoic acid 180mg/day + ezetimibe 10mg/day

Pita alone - 5 months; Pita + BA - 39 days.

Legend: Pita alone - PA; Pita + BA - P+BA; Pita + ezetimibe P+EZ

Total Cholesterol: PA - 228 mg/dL; P+BA - 208 mg/dL; P+EZ - 195 mg/dL; P+BA+EZ - 178 mg/dL
LDL-C Calc: PA - 123 mg/dL ; P+BA - 110 mg/dL; P+EZ - 99 mg/dL; P+BA+EZ - 91 mg/dL
Trig: PA - 93 mg/dL ; P+BA - 62 mg/dL; P+EZ - 82 mg/dL; P+BA+EZ - 62 mg/dL
HDL: PA - 89 mg/dL ; P+BA - 87 mg/dL; P+EZ - 81 mg/dL; P+BA+EZ - 75 mg/dL

Not exactly thrilling results. It brings me (just) under the cutoff values for hyperlipidemia as specified by the UCLA lab range. Each additional drug brings down the values by just a few points (if any - see trigs!). To say the results are underwhelming given the arsenal of drugs deployed is a depressing understatement. I’m not impressed.

Unfortunately it also represents the end of the road for me for easily available LLT drugs I have on hand. I am aware that the next currently available drug class I might add in order to crush LDL/ApoB further would be PCSK9i. However, call me excessively paranoid, but I continue to be worried by the MR AD signal for PCSK9i. That said, I’m not absolutely excluding that I might use a PCSK9i in the future. Meanwhile I am eagerly awaiting the whole slew of LLT drugs that should be coming online in the not too distant future, fingers crossed.

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#1100

91 LDL is better than what your previous numbers were. Take it as a win and look for other ways to lower your cholesterol.

#1101

This is the sort of situation where ApoB and Lp(a) would be useful measurements.

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#1102

I agree. Your apoB matters more @CronosTempi. What is it?

1 Like