"Prils & Promises: ACE Inhibitors in the Modern Era of Hypertension Therapy"

Background & Rationale: ACE inhibitors remain foundational in hypertension management, but recent evidence and emerging therapies invite re-examination of their roles, benefits, and limitations.Objective: To deliver a comprehensive, updated narrative on ACE inhibitors in arterial hypertension—covering pharmacology, clinical evidence, comparative effectiveness, safety, and future directions—with supporting research-template materials.Methods: Review and synthesis of key trials, meta-analyses, and recent comparative studies (2018–2025), combined with constructed research protocol tools (data dictionary, CRF fields, statistical plan).Results & Key Insights: ACE inhibitors lower systolic BP by ~10–15 mmHg, reduce cardiovascular events in high-risk cohorts (e.g. HOPE), and slow renal disease progression. Newer comparative real-world data show nuanced differences versus ARBs in efficacy and safety. Limitations such as lower effectiveness in certain populations (e.g. monotherapy in Black patients) and adverse effects (cough, angioedema) are highlighted. Emerging modalities like RNAi (e.g. zilebesiran) and aldosterone antagonists (e.g. baxdrostat) promise adjunctive or alternative strategies.Conclusion: ACE inhibitors continue to be a backbone in hypertension therapy, but must be used with individualized consideration. Integration with novel agents and precision strategies defines the next frontier. The appended research tools support future investigations into ACEI outcomes and comparative strategies.