Nimodipine Plus Statins Improves Brain Hemorrhage Outcomes by Restoring CGRP and Reducing Endothelin-1 Levels | Research

The takeaway

Combining nimodipine with statins for subarachnoid hemorrhage raised protective CGRP levels and lowered damaging endothelin-1, achieving a 90% response rate versus 68% with nimodipine alone in 100 patients.

90% vs. 68% response rate
Combination therapy outperformed nimodipine alone by restoring the CGRP/endothelin-1 peptide balance and reducing cerebral vasospasm after brain hemorrhage

What the researchers found

Combination therapy (nimodipine + statins) achieved 90% overall response rate versus 68% with nimodipine alone (p<0.05). After 7 days, the combination group had significantly lower endothelin-1 levels, higher CGRP levels, lower VEGF levels, higher peroxiredoxin 2 levels, and slower mean cerebral artery blood flow velocity (indicating less vasospasm). Adverse reactions occurred in only 6% of the combination group versus 20% with nimodipine alone (p<0.05).

Why it matters

Subarachnoid hemorrhage is a devastating form of stroke with high mortality. Vasospasm — dangerous brain blood vessel constriction driven by the balance between vasoconstricting peptides (endothelin-1) and vasodilating peptides (CGRP) — is a leading cause of secondary brain damage. This study shows that adding statins to nimodipine improves this critical peptide balance, directly connecting peptide biomarker changes to better patient outcomes.

How the study worked

Retrospective study of 100 subarachnoid hemorrhage patients at Baoding No.1 Central Hospital, China (March 2019-2022). Group A (n=50) received nimodipine alone; Group B (n=50) received nimodipine plus statins. Endothelin-1, CGRP, VEGF, and peroxiredoxin 2 were measured at baseline and day 7. Mean cerebral artery blood flow velocity and adverse reactions were compared. Analysis used SPSS 22.

What this study cannot tell us

This is a retrospective, non-randomized study from a single Chinese hospital, introducing selection bias and limiting generalizability. The sample size of 100 is relatively small for a clinical study. Specific statin type and dose weren't detailed in the abstract. The 7-day follow-up is short, and long-term outcomes weren't reported. The study lacks blinding, which could influence outcome assessment.

How to read the evidence

This is a retrospective observational study from a single center with 100 patients. While the results are statistically significant and clinically meaningful, the non-randomized, unblinded design limits the strength of causal conclusions.

When this study was published

Published in 2025 using data from 2019-2022, this study reflects current clinical practice for subarachnoid hemorrhage management in China.

The bigger picture

CGRP and endothelin-1 are among the most important vasoactive peptides in cerebrovascular disease. CGRP is a powerful vasodilator that protects against vasospasm, while endothelin-1 is a vasoconstrictor that worsens it. The balance between these peptides determines whether brain blood vessels stay open after hemorrhage. This study adds clinical evidence that pharmacological interventions shifting this balance toward CGRP dominance improve patient outcomes — a principle that connects to the broader CGRP-targeting migraine drug field.

Questions still open

Would direct CGRP supplementation be more effective than statins for preventing vasospasm after subarachnoid hemorrhage?
Which specific statin and dose provides the optimal shift in the CGRP/endothelin-1 balance?
Could CGRP and endothelin-1 levels at admission predict which patients are at highest risk for vasospasm?

Common questions

What role do peptides play in brain hemorrhage complications?

After a brain hemorrhage, two key peptides battle for control of brain blood vessels. CGRP (calcitonin gene-related peptide) is a powerful vasodilator that keeps blood vessels open and blood flowing. Endothelin-1 is a vasoconstrictor that narrows blood vessels. When endothelin-1 wins this battle, dangerous vasospasm occurs — blood vessels clamp down, cutting off blood supply to brain tissue. This study showed that adding statins to standard treatment shifted the balance toward CGRP, reducing vasospasm.

Why did the combination therapy have fewer side effects?

Only 6% of patients on nimodipine plus statins had adverse reactions versus 20% with nimodipine alone. While the exact reason isn't fully explained, it may relate to the improved vascular peptide balance — with more CGRP and less endothelin-1, blood vessels function more normally, potentially reducing the complications associated with abnormal vascular tone. The synergistic mechanism may also allow lower effective doses of each drug.

Read the original research

Application of nimodipine combined with statins in the treatment of subarachnoid haemorrhage.

JPMA. The Journal of the Pakistan Medical Association, 75(5), 767-771

View on PubMed ↗Publisher’s paper ↗

Citation

Zhang, Yu; Ma, Feifan; Gan, Ning; Xu, Zhijie; Jiao, Yang; Zhang, Jiancang. (2025). Application of nimodipine combined with statins in the treatment of subarachnoid haemorrhage.. JPMA. The Journal of the Pakistan Medical Association, 75(5), 767-771. https://doi.org/10.47391/JPMA.11366