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ForumsCardiovascular OutcomesNNT for MACE prevention — July 2024

NNT for MACE prevention — July 2024

gary_naperville Tue, Dec 17, 2024 at 10:59 AM 36 replies 1,910 viewsPage 1 of 8
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gary_naperville
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Oct 2024
Naperville, IL
Dec 17, 2024 at 10:59 AM#1

My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

Relative versus absolute is the distinction that gets lost: a 20% relative reduction on a high baseline risk is a large absolute benefit, and the same relative figure on a low baseline risk is a small one.

So the question, as narrowly as I can put it: how much of the SELECT benefit is plausibly independent of the weight loss, and whether that distinction changes anything practical.

I have searched first, so if this is covered somewhere point me at it and I will read it.

9 12SleepFixSam, PurityPaulOR, MaxMetOK and 6 others
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FDA_TrackerJim
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Rockville, MD
Dec 17, 2024 at 11:34 AM#2
gary_naperville said:
My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

I want to bring up the cardiovascular angle on cardiovascular risk.

The SELECT trial demonstrated a 20% reduction in MACE with semaglutide 2.4mg[1]. This is practice-changing because the CV benefit appears to be independent of the degree of weight loss — suggesting direct vascular and anti-inflammatory mechanisms.

For cardiovascular risk, this means we need to think beyond the primary outcome and consider the cardiovascular implications. The all-cause mortality reduction (HR 0.81) is the most clinically meaningful signal.

References:
[1] Lincoff AM, et al. N Engl J Med. 2023;389(24):2221-2232.
Last edited: Dec 17, 2024 at 2:34 PM
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sean_dublin
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Dublin, IE
Dec 17, 2024 at 12:09 PM#3
FDA_TrackerJim said:
I want to bring up the cardiovascular angle on cardiovascular risk.
FDA_TrackerJim said:
...cardiovascular risk is just another fad...

I understand the skepticism — we've all seen "miracle" weight loss solutions come and go. But consider what makes GLP-1 agonists different:

  • Phase 3 RCTs with thousands of participants (not 20-person pilot studies)
  • Published in NEJM, JAMA, Lancet (not press releases)
  • Replicated across multiple independent research groups
  • Proven cardiovascular and renal benefits beyond weight loss
  • Biological mechanism fully characterized at the receptor level

This isn't a fad — it's a new drug class supported by the highest level of clinical evidence. The comparison to past fads is understandable but inappropriate.

Last edited: Dec 17, 2024 at 1:09 PM
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robert_kc
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Dec 17, 2024 at 12:44 PM#4
gary_naperville said:
My reason for being on this is cardiovascular rather than cosmetic, which puts me in a small minority in most of these threads.

Mine went the same way, slower. I had assumed I was the exception until I read this.

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NurseKim_ATL
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Atlanta, GA
Dec 17, 2024 at 3:58 PM#5

Adding the clinical framing, because it changes how the question reads.

Lp(a) and cardiovascular risk: a nuance that matters. Unlike most lipid markers, Lp(a) is 90%+ genetically determined and doesn't really change with weight loss or GLP-1 therapy.

My Lp(a) has remained at 57 nmol/L across all time points. If yours is elevated (>50 nmol/L), you need additional risk mitigation strategies regardless of your GLP-1 response. Don't assume your medication is covering all cardiovascular risk factors.

Last edited: Dec 17, 2024 at 8:58 PM
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