🤔💊 Do We Even Need Statins Anymore?

Oh, hi again.

Sorry to interrupt the regularly scheduled programme. A scheduling mistake was made. So instead of getting a Deep Dive on a peaceful Sunday evening, it’s with you on your Monday morning commute. Sorry🙈.

But hey, now you’ve got something to discuss at work today, rather than the dreaded “Do anything interesting this weekend?” convo.

The question of the day is: Do We Even Need Statins Anymore?

We’re gonna take a look into statins’ past and see how they became the transcendent medication they are today…

Then look at some of the new kids on the block 👀

See how they’ve improved on the hyperlipidaemia formula and see if they have what it takes to succeed statins

If you want to read any previous editions of The Handover, you can on our website.

Ozempic wasn’t the first “miracle drug” to exist.

In ancient times (the 90s), medicine was fighting a different enemy: Cholesterol.

Did people know what cholesterol actually was? No!
Just that it was bad, and everyone needed lower levels in their diet and in their blood. 

Cholesterol = Fat. Fat = Heart Attack. Heart Attack = Death.
No one wants to die! 

Media outlets, food companies and pharma saw the opportunity and hence birthed the low-fat industrial complex. Low-Fat This. Low-Cholesterol That.
Very similar to the High-Protein craze going on today. 

For all its hysteria, there were obviously serious CVD problems that came along with having elevated LDL. 

In 1994, everything changed with the release of the 4S Study.
This study provided the first conclusive evidence that simvastatin not only lowered cholesterol but also reduced heart attacks and prolonged life in high-risk patients. 

With a tested and approved miracle status, statin fever reached an all-time high in the early 2000s.
Outside of tabloid headlines, prescriptions exploded. And in 2006, NICE made it official: anyone with a 10-year CVD risk above 20% should be on a statin.

Then we all lived happily ever after, there was never a heart attack ever again, and all cardiologists lost their jobs and became homeless. 

We all know that’s not exactly how the story went. Despite all its benefits, no drug is perfect:

Statins had drawn their critics. The same media outlets praising the miracle drugs bashed their side effects. Causing hysteria on the other side of the spectrum.

Despite many rumours being dispelled upon the release of the Nocebo Trial, statins never regained their social standing. Akin to a washed-up Hollywood celebrity after a scandal. They may be vindicated in court, but the public never truly trusts them again.

The hunt for a better medication was on…
Now in 2025, the hunt may be over.
Do these two contenders have what it takes to dethrone statins?
Let the statin succession begin.

The strongest contender was found in 2003. A mutation in the PCSK9 gene was linked to familial hypercholesterolaemia (a condition causing extremely high LDL-C levels). 

This gave the researchers the big idea to think about inhibiting PCSK9 to lower LDL.

A little pharmacology refresher…

And a big plus is that injections need to go once every 2-3 weeks, rather than every day. Hopefully, it will help with medication compliance. 

Away with the theory, now into the research:

The landmark FOURIER Trial (2017) enrolled over 27,500 patients with established atherosclerotic cardiovascular disease – all already on statins.

Adding evolocumab (a PCSK9 inhibitor) to their regimen:

Additional trials like ODYSSEY OUTCOMES and PURSUIT help back these claims.
PSCK + Statins was, in fact, a GOATed combination

To date, there have been no head-to-head trials pitting PCSK9-i against statins(more on why later).
But we do have the GAUSS-3 RCT:

So powerful. So precise. But so expensive:
PCSK9 Inhibitors will run you a pretty penny. We’re looking at £4000 per year for medication. Or £300 a month, compared to statins price of £2.58 per month. Pretty stark.

Outside of its price, the fact that it’s an injectable should be a repellent, but if people are so eager to jab themselves for GLP-1 RAs, this should be a walk in the park.

Presently, PCSK9 inhibitors remain Robin to Statins Batman.

Onto the next contender…

PCSK9 inhibitors were cute, but with Inclisiran, they’ve taken it to a whole other level. 

How it works:

Best of all, its gene-silencing nature means that it hardly needs to be administered. We’re talking about just 2 subcutaneous injections a year.

The most crucial studies that led to Inclisiran's regulatory approval were the Phase III trials from the ORION program, ORION-10 and ORION-11.

These trials established the effectiveness of Inclisiran across a broad patient population:

Although being approved in 2020, Inclisiran has yet to be definitively proven to improve cardiovascular outcomes. The ORION-4 trial is an ongoing study aiming to prove exactly. The trial results are highly anticipated and will be released at some point next year. 

Watch this space.

They might just… but we’ll likely never know. 

Every study to date starts with the same rule: patients must already be on a maximally tolerated statin dosage. 

This is because to take them off the statin(a drug proven to save lives) and randomise them to a group with either a PCSK9 inhibitor or Inclisiran would be unethical. Statins are a really good drug! It’s a funny predicament to be in.

So even if these new hopefuls were better, a randomised trial pitting them against statins is very unlikely to be approved and take place.
Without this research, guideline and policy reform cannot take place. We’ll likely never conclusively be able to say these medications are better than statins.

So for now, they’ll need to battle amongst themselves for the role of playing second fiddle.

Handover Over 🫡

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