Long-term outcomes of ischaemia with no obstructive coronary artery disease (INOCA): a systematic review and meta-analysis

Abstract

Background The prognosis of myocardial ischaemia with no obstructive coronary artery disease (INOCA) and its underlying vasomotor disorders, vasospastic angina (VSA) and microvascular angina (MVA), is not well defined. The aim of this study was to perform a systematic review and meta-analysis of studies evaluating the long-term prognosis of patients with INOCA.Methods We included studies evaluating the prognosis of patients with INOCA published between January 1984 and August 2023 in Medline, Embase, Web of Science and Cochrane databases. Studies were selected if they included patients who fulfilled the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria for either possible or definitive VSA or MVA. The primary outcomes were composite of all-cause death and myocardial infarction (MI), and major adverse cardiovascular event (MACE) at annual intervals up to 5-year follow-up. The incidence of primary outcomes for INOCA, each INOCA endotype and by method used to determine the diagnosis was calculated using the random effects model.Results Fifty-four studies (17 302 patients) meeting the eligibility criteria were selected. The rate of all-cause death and MI with VSA was 0.7 (95% CI 0.4 to 1.0)/100 patient-years and with MVA was 1.1 (95% CI 0.7 to 1.5)/100 patient-years (p>0.05). The rate of MACE with VSA was 1.1 (95% CI 0.5 to 1.9)/100 patient-years and with MVA was 2.5 (95% CI 1.6 to 3.6)/100 patient-years (p=0.025). Patients with reduced coronary flow reserve (CFR) had higher all-cause death and MI rates than patients whose diagnosis of MVA was established based on an abnormal exercise or imaging stress test (4.7 (95% CI 2.0 to 8.4) vs 0.5 (95% CI 0.1 to 1.1) vs 1.1 (95% CI 0.5 to 2.0)/100 patient-years, p=0.001).Conclusions Overall, patients with INOCA have a low rate of MACEs, but patients with MVA, especially those with reduced CFR, have a significantly higher rate of MACE than other subgroups, although there is high heterogeneity among the included studies.PROSPERO registration number CRD42021275070.