Treatment Modalities for Angina with Non-Obstructive Coronary Arteries (ANOCA): A Systematic Review and Meta-Analysis

Background and Objectives: Up to 40% of patients undergoing a coronary angiogram due to angina pectoris have no obstructive coronary artery disease, also known as angina with non-obstructive coronary arteries (ANOCA). ANOCA is associated with significant impairment in patients' quality of life, increased risk of myocardial infarction and all-cause mortality. Approximately 25% of patients with ANOCA have persisting symptoms despite optimal medical therapy. There is a lack of in-depth knowledge regarding tailored treatment for patients with ANOCA due to a scarcity of trials designed to assess the effect of treatment modalities. The aim of this systematic review and meta-analysis is to give clinicians an overview of the efficacy of current treatment modalities for patients with ANOCA. Methods: PudMed/MEDLINE, Embase, the Cochrane Library and clinical trial registries were searched for randomised controlled and cohort studies regarding treatment modalities for ANOCA. The main outcome was change in angina pectoris frequency for each treatment modality. Secondary outcomes included changes in exercise capacity, quality of life, Canadian Cardiovascular Society (CCS) class, coronary flow reserve (CFR) and survival. Results: In total, 80 studies were included and used in the meta-analysis, of which ten studies met the current definition of ANOCA. Angina pectoris frequency improved significantly in the majority of the treatment modalities, with neuromodulation resulting in -3.35 standardised mean difference (SMD) (95% CI: -5.13; -1.56), trimetazidine in -1.74 SMD (-2.63; -0.85), traditional Chinese medicine in -1.55 SMD (-2.36; -0.75), beta-blockers in -1.32 SMD (-1.88; -0.77), enhanced external counterpulsation in -1.27 SMD (-2.04; -0.49), stem cell therapy in -1.04 SMD (-1.51; -0.57), lifestyle interventions in -0.86 SMD (-1.15; -0.57), RAAS-inhibitors in -0.83 SMD (-1.31; -0.35) and calcium channel blockers in -0.64 SMD (-0.92; -0.35). Conclusions: This meta-analysis into treatment modalities for patients with ANOCA shows a significant improvement in angina pectoris frequency in the majority of included treatment modalities. However, these results should be interpreted cautiously, as only ten of the studies included in the meta-analysis meet the current definition of ANOCA. This review underlines the importance of undertaking new studies with existing treatment modalities to determine the efficacy in patients with ANOCA.