Abstract
International guidance increasingly permits calcitonin gene-related peptide (CGRP)-targeted therapies to be considered at the initial preventive-treatment decision, but clinical eligibility does not ensure registration, reimbursement, practical access, or first prescribing. We reviewed contemporary preventive evidence and used the six Gulf Cooperation Council (GCC) health systems as a regional test case for this evidence-to-access gap. This structured evidence review used a focused PubMed/MEDLINE working set of 2,443 records through September 1, 2026, complementary bibliographic and trial-registry searches, professional guidance, and targeted GCC regulatory, procurement, and real-world sources. Prioritized assessment included 248 full texts and a 135-document working evidence corpus. A targeted update on September 29, 2026 checked for additional major guidance and head-to-head evidence without altering the original numerical workflow. Network meta-analyses support efficacy across several established and CGRP-targeted preventives but do not establish a simple class hierarchy. In their respective trials, HER-MES and TEMPLE reported lower adverse-event discontinuation and higher at least 50% responder rates with erenumab and atogepant than with topiramate; their populations and single-comparator designs limit generalization to universal first-treatment superiority. AAN/AHS 2026 emphasizes individualized choice; NICE and 2026 BASH guidance illustrate how national access pathways can remain sequential. Public GCC evidence is uneven, with the clearest clinical and regulatory documentation in the United Arab Emirates, Saudi Arabia, and Kuwait and important transparency gaps elsewhere. We therefore propose a five-layer implementation audit separating scientific eligibility, regulatory availability, clinical preference, reimbursement/formulary eligibility, and actual prescribing. The resulting patient-stratified framework preserves conventional-first, CGRP-targeted-first, and phenotype/comorbidity-driven pathways. The principal implication is not universal CGRP-first prescribing, but explicit separation of evidence-based choice from health-system access rules, with outcome-based reassessment and country-specific economic evaluation.