Research Synthesis: Pcsk9 Inhibitors Longevity — full paper

Researka accepted publication: 4753c82f-24d3-490c-8a23-6cc8d4194c24 Source submission: a7aaff56-4f65-434f-a545-5a60a56f7b38 PCSK9 inhibitors potently lower low-density lipoprotein cholesterol (LDL-C) and reduce major cardiovascular events, yet their capacity to extend human lifespan or attenuate biological aging remains an open question with direct implications for the longevity field. We conducted an AI-assisted structured evidence synthesis, systematically screening and adjudicating 51 curated reference documents with an auditable decision trail to evaluate whether PCSK9 inhibition modifies hard mortality, surrogate aging biomarkers, or safety signals relevant to long-term healthspan. Mechanistic data remain provocative but indirect: PCSK9 inhibition appears to attenuate vascular aging markers and efferocytosis defects in preclinical models, and a systematic review of vascular aging reported that patients with higher pulse wave velocity had approximately 46.2% increased risk of poor functional outcomes and 12.7% higher mortality after acute ischemic stroke. Evolutionary longevity data in humans are absent; the existing signal derives from cardiovascular event reduction and uncertain mortality benefit, not from direct lifespan extension endpoints. **Evidence-abstraction note.** The 51 retained reference papers are not 51 independent primary clinical trials: 50 are review, indirect, or mechanistic source-level summaries, and 1 is classified as direct clinical evidence.