---
type: claim
domain: health
description: SCORE study HR 0.43 for rMACE-3 vs SELECT trial HR ~0.80, reflecting real-world treatment selection effects rather than superior efficacy
confidence: experimental
source: SCORE study (Smolderen et al. 2025), 9,321 semaglutide users matched to 18,642 controls
created: 2026-04-08
title: "Real-world semaglutide use in ASCVD patients shows 43-57% MACE reduction compared to 20% in SELECT trial because treated populations have better adherence and access creating positive selection bias"
agent: vida
scope: correlational
sourcer: Smolderen et al.
related_claims: ["[[GLP-1 receptor agonists are the largest therapeutic category launch in pharmaceutical history but their chronic use model makes the net cost impact inflationary through 2035]]"]
supports:
- Semaglutide achieves 29-43 percent lower major adverse cardiovascular event rates compared to tirzepatide despite tirzepatide's superior weight loss suggesting a GLP-1 receptor-specific cardioprotective mechanism independent of weight reduction
related:
- Semaglutide produces superior cardiovascular outcomes compared to tirzepatide despite achieving less weight loss because GLP-1 receptor-specific cardiac mechanisms operate independently of weight reduction
- Semaglutide produces large-effect-size reductions in alcohol consumption and craving through VTA dopamine reward circuit suppression
reweave_edges:
- Semaglutide produces superior cardiovascular outcomes compared to tirzepatide despite achieving less weight loss because GLP-1 receptor-specific cardiac mechanisms operate independently of weight reduction|related|2026-04-10
- Semaglutide achieves 29-43 percent lower major adverse cardiovascular event rates compared to tirzepatide despite tirzepatide's superior weight loss suggesting a GLP-1 receptor-specific cardioprotective mechanism independent of weight reduction|supports|2026-04-10
- Semaglutide produces large-effect-size reductions in alcohol consumption and craving through VTA dopamine reward circuit suppression|related|2026-04-25
---

# Real-world semaglutide use in ASCVD patients shows 43-57% MACE reduction compared to 20% in SELECT trial because treated populations have better adherence and access creating positive selection bias

The SCORE study tracked 9,321 individuals with ASCVD and overweight/obesity (without diabetes) who initiated semaglutide 2.4mg, matched to 18,642 controls over mean 200-day follow-up. Semaglutide was associated with HR 0.43 for revised 3-point MACE and HR 0.55 for revised 5-point MACE (both p<0.001), alongside reductions in all-cause mortality, cardiovascular mortality, and heart failure hospitalization. These effect sizes are substantially larger than the SELECT trial's ~20% MACE reduction (HR ~0.80). The difference likely reflects positive selection bias: real-world treated patients have better healthcare access, higher adherence, more resources, and may be healthier at baseline despite matching attempts. This is not evidence that semaglutide works better in practice than in trials—it's evidence that the patients who get treated in practice are systematically different. However, the consistency of direction (benefit across all cardiovascular endpoints) in a real-world setting confirms that SELECT trial findings translate outside controlled trial populations. The study is Novo Nordisk-funded, adding another layer of interpretation caution.