Emerging antihypertensive therapies and cardiovascular, kidney, and metabolic outcomes: a Mendelian randomization study
Authors' conclusion
Our study highlights the potential of PDE5i, sGCs, ERA, and AGTi in reducing cardiovascular and renal risks. These findings underscore the necessity for targeted clinical trials to validate the efficacy and safety of these therapies.
Study context
- Population
- European-ancestry genome-wide association studies (GWAS) and genotype-tissue expression version 8 data for 29 tissues
- Comparison
- Genetically proxied drug effect on coronary artery disease (CAD), myocardial infarction (MI), ischaemic stroke, atrial fibrillation (AF), heart failure (HF), T2D and chronic kidney disease (CKD)
- Outcome
- All outcomes, genetically predicted SBP reduction
Methodological detailssummary-based mendelian randomization (MR) (SMR), colocalization analyses
- Summary-based MR (SMR)
- Colocalization analyses
Main finding
As reported in the abstract
- Genetically predicted systolic blood pressure (SBP) reduction was associated with reduced risks of all outcomes
Further findings
CAD and ischaemic stroke, PDE5i
| Comparison | OR per 10-mmHg decrease in SBP (95% CI) | |
|---|---|---|
| PDE5iCAD | 0.348 (0.199–0.607) | |
| PDE5iIschaemic stroke | 0.588 (0.453–0.763) | |
| 0.20.5125Odds ratio per 10-mmHg decrease in SBP (log scale) |
CAD, MI and CKD, soluble guanylate cyclase stimulators (sGCs)
| Comparison | OR per 10-mmHg decrease in SBP (95% CI) | |
|---|---|---|
| sGCsCAD | 0.332 (0.236–0.469) | |
| sGCsMI | 0.238 (0.168–0.337) | |
| sGCsCKD | 0.55 (0.398–0.761) | |
| 0.10.31310Odds ratio per 10-mmHg decrease in SBP (log scale) |
CAD and ischaemic stroke, ERA and AGTi
- ERA and AGTi showed protective effects against CAD and ischaemic stroke
SMR and colocalization, CAD and MI
- SMR and colocalization supported the association of gene expression levels of GUCY1A3 and PDE5A with CAD and MI risk
Original publication
Emerging antihypertensive therapies and cardiovascular, kidney, and metabolic outcomes: a Mendelian randomization study. Eur Heart J Cardiovasc Pharmacother. Published 17 February 2025. doi:10.
Summarised from the published abstract; every number is checked against it