Published online Oct 19, 2026. doi: 10.5498/wjp.121270
Revised: June 10, 2026
Accepted: July 15, 2026
Published online: October 19, 2026
Processing time: 170 Days and 23.9 Hours
Post-cerebral infarction depression (PCID) refers to a common neuropsychiatric sequela present in 33%-45% of cerebral infarction survivors, greatly more than that of the general population; it negatively affects the process of neurologic recovery and is associated with increased mortality rates and lower quality of life. Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, especially evolocumab, have demonstrated pleiotropic effects beyond regulation of lipids with effectiveness some anti-inflammatory and possible neuroprotective activity. Nevertheless, the impact of evolocumab-based intensive lipid-lowering therapy on prognosis in PCID patients has not been thoroughly investigated.
To investigate the impact of evolocumab-based intensive lipid-lowering therapy on clinical prognosis, including depression remission, functional recovery, cog
This was a retrospective study of 144 patients with PCID enrolled from January 2022 to June 2025 at two tertiary hospitals. Patients were allocated to the intensive group (n = 72, evolocumab 140 mg biweekly plus rosuvastatin 10 mg daily) or the standard group (n = 72, rosuvastatin 10 mg daily) according to the lipid-lowering regimens prescribed by their attending physicians in routine clinical practice. The primary endpoint was depression remission rate [17-item Hamilton Depression Rating Scale (HAMD-17) < 7] at 24 weeks. Secondary endpoints were HAMD-17 and Hamilton Anxiety Rating Scale score trajectory, serum PCSK9 and lipid profile, inflammatory markers (interleukin-6, tumor necrosis factor-alpha, high-sensitivity C-reactive protein), cognitive function (Montreal Cognitive Assessment), functional in
A total of 72 pairs were analyzed after using propensity score matching. The remission rate of depression at 24 weeks was significantly higher in the intensive group (58.3% vs 31.9%, P = 0.001). The reduction in HAMD-17 scores was significantly greater in the intensive group at 12 weeks (11.4 ± 3.3 vs 15.2 ± 4.1, P < 0.001) as well as at 24 weeks (7.8 ± 2.9 vs 12.5 ± 3.6, P < 0.001). In the intensive group, the serum PCSK9 level decreased to 148.7 ± 38.5 ng/mL compared with 285.3 ± 62.4 ng/mL in the standard group at 24 weeks (P < 0.001). The intensive group had significantly lower inflammatory markers (interleukin: 2.8 ± 0.7 pg/mL vs 4.9 ± 1.1 pg/mL, P < 0.001), higher cognitive recovery (Montreal Cognitive Assessment: 26.2 ± 1.9 vs 23.8 ± 2.5, P < 0.001), and improved functional performance outcomes (modified Rankin Scale 0-2: 72.2% vs 51.4%, P = 0.009). The intensive group had lower rates of recurrent cerebrovascular events (4.2% vs 12.5%, P = 0.065), and all-cause rehospitalization was significantly decreased (15.3% vs 30.6%, P = 0.027).
Patients with coronary artery disease already benefit from intensive lipid-lowering therapy with evolocumab, which has been shown to significantly enhance depression remission and functional independence in addition to improving their cognitive performance and reducing the burden of inflammation (high-sensitivity C-reactive protein) and rehospitalization rates. Altogether, these observations provided evidence for evolocumab to be an extensive adjunctive approach to amelioration of multidimensional prognosis in post-ischemic stroke depression.
Core Tip: This retrospective study shows that evolocumab lipid-lowering therapy greatly ameliorates the multi-dimensional prognosis in patients with post-cerebral infarction depression. The remission rates for depression nearly doubled (58.3% vs 31.9%) associated with concurrent improvements in cognition, functional independence, and rehospitalization. This parallel reduction in inflammatory markers with proprotein convertase subtilisin/kexin type 9 further supports a neuroinflammation-mediated mechanism. These results delineate evolocumab as an approach with dual therapeutic implications mitigating cardiovascular risk and neuropsychiatric sequelae in patients post-cerebral infarction.