← GLP-1 receptor agonists × cardiovascular events

Observational studyBMC cardiovascular disorders2025

Combining genetic proxies of drug targets and time-to-event analyses from longitudinal observational data to identify target patient populations.

Luke Zhang et al.PubMed ↗Full text ↗Publisher ↗

  • Genetic proxy for PCSK9 inhibition (rs11591147)looks good hereLower survival from CV death/heart transplant.Correlation only, not a test of it.
  • Genetic proxy for beta-blockade (rs7076938)looks good hereFewer freedom from rehospitalization or deaths.Correlation only, not a test of it.
  • Genetic proxy of ACE inhibition (rs7076938)looks good hereFewer freedom from rehospitalization for HF or deaths, lower AF.Correlation only, not a test of it.
  • Protective variant in GLP1R (rs10305492)looks good hereFewer developing HF or CV deaths.Correlation only, not a test of it.

What moved togetherboth groups pooled, not the treatment’s effect

Correlation, not cause

Genetic proxy for PCSK9 inhibition (rs11591147) went with lower survival from CV death/heart transplant

−22%

genetic proxy for PCSK9 inhibition (rs11591147) vs no genetic proxy for PCSK9 inhibition (rs11591147), in individuals following a diagnosis of ischemic heart disease

Bigger than 5 in 10 for cardiovascular events

As reported

HR 0.78, no interval

Correlation, not cause

Genetic proxy for beta-blockade (rs7076938) went with fewer freedom from rehospitalization or deaths

−8%

genetic proxy for beta-blockade (rs7076938) vs no genetic proxy for beta-blockade (rs7076938), in individuals with AF

Bigger than 3 in 10 for adverse events & safety

As reported

HR 0.92, no interval · the paper's word: freedom from rehospitalization or death

Correlation, not cause

Genetic proxy of ACE inhibition (rs7076938) went with fewer freedom from rehospitalization for HF or deaths

−20%

genetic proxy of ACE inhibition (rs7076938) vs no genetic proxy of ACE inhibition (rs7076938)

Bigger than 4 in 10 for cardiovascular events

As reported

HR 0.8, no interval · the paper's word: freedom from rehospitalization for HF or death

+4 more in the walkthrough ↓

Who was studied, and how

people with arrhythmia, in this paper

Already taking genetic proxy for PCSK9 inhibition (rs11591147), or nottheir own situation, not assigned

on genetic proxy for PCSK9 inhibition (rs11591147)
not on genetic proxy for PCSK9 inhibition (rs11591147)

Genetic proxy for PCSK9 inhibition (rs11591147) went with lower survival from CV death/heart transplant−22%

correlation, not a test

Already taking genetic proxy for beta-blockade (rs7076938), or nottheir own situation, not assigned

on genetic proxy for beta-blockade (rs7076938)
not on genetic proxy for beta-blockade (rs7076938)

Genetic proxy for beta-blockade (rs7076938) went with fewer freedom from rehospitalization or deaths−8%

correlation, not a test

the abstract, start to end

… heart disease (Hazard Ratio (HR) 0.78, P = 0.03).

… or death in individuals with AF (HR 0.92, P = 0.001), and a genetic proxy of ACE inhibition (rs7076938) improved freedom from rehospitalization for HF or death (HR 0.8, P = 0.017) and AF (HR 0.85, P = 0.0014).

… of ischemic heart disease (HR = 0.82, P = 0.031) and a protective variant in ABCC8 (rs757110) showed decreased risk of CV mortality since ischemic disease diagnosis (HR = 0.88, P = 0.04) and decreased risk of AF in diabetic patients with ischemic heart disease (HR = 0.68, P = 0.001).

← favours treatmentfavours comparator →
could be chance
No interval given · direction only, strength unknown
Survival from CV death/heart transplantgenetic proxy for PCSK9 inhibition (rs11591147) vs no genetic proxy for PCSK9 inhibition (rs11591147), in individuals following a diagnosis of ischemic heart disease
HR 0.78
Freedom from rehospitalization or deathgenetic proxy for beta-blockade (rs7076938) vs no genetic proxy for beta-blockade (rs7076938), in individuals with AF
HR 0.92
Freedom from rehospitalization for HF or deathgenetic proxy of ACE inhibition (rs7076938) vs no genetic proxy of ACE inhibition (rs7076938)
HR 0.8
AFgenetic proxy of ACE inhibition (rs7076938) vs no genetic proxy of ACE inhibition (rs7076938)
HR 0.85
Developing HF or CV deathprotective variant in GLP1R (rs10305492) vs no protective variant in GLP1R (rs10305492), in after diagnosis of ischemic heart disease
HR 0.82
CV mortality since ischemic disease diagnosisprotective variant in ABCC8 (rs757110) vs no protective variant in ABCC8 (rs757110)
HR 0.88
AFprotective variant in ABCC8 (rs757110) vs no protective variant in ABCC8 (rs757110), in diabetic patients with ischemic heart disease
HR 0.68
PCSK9 inhibitorsGLP-1 receptor agonistsInvestigational compoundsCardiovascular eventsAdverse events & safety
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1 paper cites it

2025
this papercites it
Full record →Abstract, authors, funding and every citing paper · PMID 40335923