心血管健康

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Patterns of Statin Therapy Use and Associated Outcomes in Older Veterans Across Kidney Function 2024

There was a higher rate of incident dementia in the No Statin group (4.7%) versus the Statin group (3.2%). Additionally, we observed a 22% all-cause mortality benefit associated with statin therapy.

Does anyone have access to the full paper?

Anyway, I’ve just started ezetimibe 10 mg. If it’s not enough to lower my ApoB I’ll reconsider atorvastatin 10 mg. (Still praying for obicetrapib to show amazing results and to be approved in the next 12 months )

[AnUser]

@adssx

(Still praying for obicetrapib to show amazing results and to be approved in the next 12 months )

What data is that, isn’t it just lipid lowering in 300 patients with FH? I don’t think you will have enough data that makes it look better than any other drugs at that point then?

[Neo]

@AnUser

enough data that makes it look better than any other drugs at that point then?

Strong MR data does add to its story + Lp(a) down for those where that is relevant (>20% of population) + potential benefit of HDL/APO A up?

[AnUser]

You’re really going to take a drug based on a study on 300 people without outcomes in exclusion of other drugs with larger trials and with outcomes?

[Neo]

Who said that?

I was as just saying that there is more data than the 300 patients

Is personally def think twice to use a new approved med in the beginning if there are relatively good alternatives. (And probably even where there are no alternatives- eg re Lp(a) for me).

(Btw, think that the number of patients across their trials is larger than 300)

[adssx]

Exactly. Also:

• Improves insulin sensitivity in people with or without diabetes: The effect of CETP inhibitors on new-onset diabetes: a systematic review and meta-analysis - PMC
• ApoA1 increase might be neuroprotective: https://twitter.com/JohnKastelein/status/1773734687007023192
• Synergistic effect with ezetimibe (instead of just additive effect): Program Planner
• Safety profile similar (if not better!) to placebo: Obicetrapib (CETP inhibitor for dyslipidemia) - #43 by adssx
• Oral
• No food effect
• Decreases small dense LDL more

[adssx]

@Neo

(Btw, think that the number of patients across their trials is larger than 300)

Yes, BROADWAY, which is due to finish in September, has 2.5k patients. PREVAIL (until 2026) has 9k participants. And they have smaller trials with 100–400 participants.

[AnUser]

This reminded me of inclisiran which is approved because it lowers LDL, meanwhile as larger trials are underway (it works via PCSK9 but only needs to be taken twice yearly).

One 16000 person trial, ORION-4:
https://www.orion4trial.org/homepage-uk

One 14000 person trial, VICTORION-1 PREVENT:

A Study of Inclisiran to Prevent Cardiovascular Events in High-risk Primary...

And apparently another 17000 person trial, VICTORION-2P:
https://clinicaltrials.gov/study/NCT05030428

[AnUser]

I just don’t see how realistically it could be a replacement for atorvastatin this year or the next.

[adssx]

If obicetrapib is as good as preliminary data and MR suggest, then it could be a replacement for atorvastatin, at the very least for statin-intolerant people and for people with uncontrolled diabetes (despite being on antidiabetic drugs). Also for people with Parkinson’s disease?

[AnUser]

I don’t know about uncontrolled diabetes but statins are indicated still for those with diabetes. If obicetrapib is better than PCSK9 inhibitors or bempedoic acid for statin intolerant at that point it seems unlikely to me. Just let’s not get caught up in the storm of stories. Hard endpoints in clinical trials matter a lot although MR is nice.

@adssx

Anyway, I’ve just started ezetimibe 10 mg

Have you taken a look at the large clinical trials?
(I can recommend if interested adding a column in clinicaltrials.gov with enrollment then downloading the excel file and sorting by size). But I can take a look, I am mostly interested in cardiovascular death as I’ve heard ezetimibe reduces it.

[adssx]

No need to fight about obicetrapib, let’s wait for the results.

@AnUser

Have you taken a look at the large clinical trials?

Not really. Other than those we’ve already discussed showing potential benefits of ezetimibe as an add-on to statins, especially in men:

• Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis 2023
• Effect of moderate-intensity statin with ezetimibe combination vs. high-intensity statin therapy according to sex in patients with atherosclerosis 2023

Interesting (but non-statistically significant) trend in men as well here: Unraveling Potential Sex‐Specific Effects of Cardiovascular Medications on Longevity Using Mendelian Randomization 2023

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The Canadian “umbrella systematic review of systematic reviews” says:

Since publication of the included systematic reviews, 2 new ezetimibe RCTs have been published. A 2019 open-label RCT compared 10 mg of ezetimibe once a day versus no treatment (no other lipid-lowering therapies were allowed) in 3796 participants 75 years and older without a history of coronary artery disease (CAD) for approximately 4 years.46 Ezetimibe significantly reduced the incidence of the composite outcome of sudden cardiac death, fatal and nonfatal MI, coronary revascularization, or fatal and nonfatal stroke by approximately 35% (ezetimibe 5.2% vs 7.8%) but had no effect on all-cause mortality. However, the trial had multiple major limitations (only 63% of the planned sample size enrolled, the trial had an open-label design, and 28% of participants withdrew or were lost to follow-up).

Here’s the trial: Ezetimibe Lipid-Lowering Trial on Prevention of Atherosclerotic Cardiovascular Disease in 75 or Older (EWTOPIA 75) 2019

The mortality curve for ezetimibe doesn’t look great I must say :

[Virilius]

P=0.43 for acm means no statistically significant difference, not even a trend.

[AnUser]

I looked at all the large trials, it seems only IMRPOVE-IT will inform our decision on the clinical trial side for ezetimibe. I’ll have to read it again carefully but it decreases composites, non-fatal MI’s, stroke, no detection of all-cause mortality and no decrease in cardiovascular deaths unlike what I have heard. It’s interesting ezetimibe decreases stroke if it it’s only active in the gut, so that means serum LDL have an effect on that?

https://www.nejm.org/doi/full/10.1056/NEJMoa1410489

That ACM curve might just be random risk, ACM can be very noisy like if someone slipped on a banana peel in the ezetimibe group, unrelated to the drug. Needs very large trials and duration especially for something with not a large effect on LDL like ezetimibe.

No between-group differences in cardiovascular mortality or in the rate of death from any cause were anticipated or observed in IMPROVE-IT, findings that are consistent with those in trials of intensive-dose versus standard-dose statin therapy.

[L_H]

For all the noise in the ACM data, it would be nice to see a benefit in ACM for once, even if it’s not statistically significant.
Given that cvd accounts for a major % of all cause deaths in the age cohort, and banana peel deaths are pretty rare, it’s interesting that multiple studies find a cvd benefit but a non-statistically-significant increase in ACM.
I wonder they’re dying of.

[Virilius]

@L_H

but a non-statistically-significant increase in ACM.

What you’re refering to is a trend with a p value of 0.06-0.15 or so. A p value of 0.43 is meaningless noise.

[adssx]

Yes but the absence of any trend towards ACM reduction is disappointing after 5y of use in a large trial.

[L_H]

Yes but the absence of any positive sign of ACM benefit is disappointing after almost 5 years. It’s a large trial and well over a third of deaths are from cvd in that cohort. So the fact that acm is numerically higher in the ezetimibe group is… “disappointing”

[AnUser]

It wasn’t a blinded placebo-controlled trial.