RESEARKA

Within the cardiometabolic corpus, several tensions emerge that temper the strength of the evidence. Liu 2023 reported null findings on direct cardiometabolic endpoints despite demonstrating mechanistic plausibility in endothelial cells, contrasting with Wang 2022, which reported an unclear overall effect direction across its network meta-analysis. Bruggen 2024 documented negative signals through identification of baseline imbalances that could confound trial outcomes, while Azizzadeh 2026 reported null findings at the observational cohort level. The disagreement between Bruggen 2024, which flagged potential methodological concerns in trial design, and Wang 2022, which reported favorable mortality reductions, highlights the importance of scrutinizing trial-level heterogeneity. These cross-study discrepancies underscore that the cardiometabolic case for PCSK9 inhibitors as longevity agents remains context-dependent and unresolved.

Citation Support

• source_1 Ma 2025
• source_2 Schwartz 2021
• source_3 Lehrke 2024
• source_4 Imran 2023
• source_5 Faraidy 2023