Exploring the Association Between Statins Use or HMG-CoA Reductase Inhibition and Migraine Risk Reduction and Disease Prophylaxis: A Comprehensive Systematic Review and Meta-Analysis
Hamdy Makhlouf1, Amr K. Hassan2, Nereen Almosilhy3, Ahmed S.A osman1, Shrouk Ramadan4, Moaz Elsayed Abouelmagd5
1Faculty of Medicine, Minia University, Minia, Egypt, 2School of Medicine, University of California, Irvine, CA, USA, 3Department of Pharmacology and Toxicology, Faculty of Pharmacy, Tanta University, Egypt, 4Ain Shams University of Medicine, Cairo, Egypt, 5Faculty of Medicine, Cairo University, Cairo, Egypt
Objective:
A growing body of research suggests that statins are associated with less risk of migraine, albeit inconclusive. We aim to investigate the nature and strength of the effect of statins on the prophylaxis of migraines.
Background:
Statins or 3‑hydroxy‑3‑methyl‑glutarylcoenzyme A (HMG‑CoA) reductase (HMGCR) inhibitors are medications that act through reducing the cholesterol content of liver cells. They have been found improve endothelial function and reduce vascular wall inflammation.
Design/Methods:
We conducted a comprehensive systematic search PubMed, Scopus, Web of Science, and the Cochrane Library, from their inception until October 2024, to include any primary study on migraine patients who received Statins. The outcomes of interest involved the association of the HMGCR gene as well as statins with the risk of migraine.
Results:
Thirteen primary studies were included in our systematic review, including 8 studies in the meta-analysis. The presence of HMGCR gene was significantly associated with higher odds of developing migraine (OR= 1.44, 95% CI= [1.30, 1.59]; P < 0.001). There is no significant association between statin use or HMGCR inhibitors and a reduced risk of migraine (OR= 0.82, 95% CI= [0.60, 1.12]; P= 0.22, I2= 89%; P< 0.001). However, after resolving heterogeneity, there was a significant reduction in the risk of migraines with HMGCR inhibitors intake (OR= 0.72, 95% CI = [0.60, 0.85]; P< 0.001, I2 = 0%; P= 0.69). A meta-analysis of two Randomized controlled trials (RCTs) showed that statins significantly reduced monthly migraine frequency (MD= -3.16, 95% CI= [-5.79, -0.53]; p = 0.02).
Conclusions:
Observational studies indicate that the HMGCR gene is significantly associated with a higher risk of migraine while RCTs prove the efficacy of statins in reducing migraine frequency compared to placebo and other drugs. However, the variability in study designs hinders definitive conclusions so larger studies are required to ascertain both findings.
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