A systematic review of enrolment criteria and treatment efficacy for microvascular angina

Microvascular angina (MVA) is an important contributor to morbidity and mortality in patients with non-obstructive coronary artery disease. Despite improvements in its recognition and diagnosis, uncertainty remains around the most effective treatment strategy, and more data are needed. We aimed to evaluate the quality of patient selection in treatment studies of MVA and provide a contemporary overview of the evidence base for the treatment of MVA. PubMed, the Cochrane Library and Google Scholar were searched from inception to 4 November 2023 for all treatment studies in patients with angina and non-obstructive coronary artery disease or coronary microvascular dysfunction. Populations with acute coronary syndrome were excluded (PROSPERO: CRD42023383075). Forty-three studies were included. By contemporary definitions of MVA according to the Coronary Vasomotor Disorders International Study Group criteria, 11 (26%) studies enrolled patients with "definitive" MVA, 24 (56%) with "suspected" MVA, and 8 (19%) did not enrol patients who met the diagnostic criteria. A total of 24 unique treatment interventions were investigated. Most studies were observational and single armed (12/24, 50%) or had a single randomised study (9/24, 38%). Ranolazine is the most well-studied intervention drug. Double-blind randomised controlled trials of ranolazine (n=6) have shown inconsistent improvements in Seattle Angina Questionnaire scores and coronary flow reserve with short-term follow-up. Treatment studies of MVA enrolled a heterogeneous population, with only a quarter meeting contemporary diagnostic criteria for definitive MVA. There is a paucity of high quality, randomised data to support any specific treatment intervention. Larger studies with robust selection criteria, blinded patient-reported outcomes, and long-term follow-up are needed.