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Current Evidence-Based Treatment of Angina With Nonobstructive Coronary Arteries (ANOCA)

Olga Toleva, Nathaniel R. Smilowitz, Odayme Quesada, Manoj Kesarwani, Michael P. Savage, Megha Prasad, Ailin Barseghian El-Farra, Noa Holoshitz, Jeffrey W. Moses, William F. Fearon, Jennifer A. Tremmel, Bruce Samuels, Timothy D. Henry, Journal of the Society for Cardiovascular Angiography & Interventions, Volume 0, Issue 0, 102633. https://doi.org/10.1016/j.jscai.2025.102633

Abstract

Although the techniques for coronary function testing (CFT) were largely developed more than 30 years ago, consensus on the specific diagnostic criteria and endotypes is still lacking. Furthermore, the management of patients with angina with nonobstructive coronary arteries (ANOCA) is challenging for most cardiologists. These patients are often a burden to the health care system due to recurrent presentations to the emergency room, repeated coronary angiography, and lack of improvement in their anginal symptoms even after being properly diagnosed with CFT. Therapies for coronary microvascular dysfunction, coronary vasospasm, and myocardial bridging have been tested in small trials and only a few randomized controlled trials. However, we are still limited in the options of therapies that we can offer to our patients. Although techniques and principles of CFT have advanced significantly, the art of managing patients with ANOCA is very challenging. A dedicated comprehensive summary of all contemporary treatment options for ANOCA is needed to guide clinicians in managing this challenging population of patients. This article subdivides ANOCA into 3 major categories: coronary microvascular dysfunction, coronary vasospasm, and myocardial bridging. Patients with ANOCA may present with 1 or a combination of the described categories. We describe major pillars in managing ANOCA patients: risk factors and lifestyle changes, traditional pharmacotherapy, device therapies, and novel approaches. We offer a summary of most evidence-based trials and scientific data on therapies for patients with ANOCA. This summary of available data about therapies aims to improve practitioners’ knowledge and give more scientific merit to the care of patients with ANOCA.

Introduction

Nearly half of patients with stable angina and/or ischemia do not have obstructive epicardial coronary disease. Angina with nonobstructive coronary arteries (ANOCA) has several underlying mechanisms that can be determined by invasive coronary function testing (CFT), including coronary microvascular dysfunction (CMD), microvascular spasm, endothelial dysfunction, epicardial coronary vasospasm, or myocardial bridging. Patients with ANOCA are best managed with therapies specific to the underlying disorder.

Clinical practice guidelines recognize the clinical impact of ANOCA and recommend CFT to define ANOCA endotypes and appropriate treatment. In some instances, patients previously treated for obstructive coronary artery disease (CAD) may have persistent angina related to unrecognized CMD, vasospasm, or myocardial bridging, despite successful epicardial coronary revascularization. Optimal medical treatment for these conditions remains challenging due to the potential for multiple superimposed mechanisms and the absence of large, randomized controlled trials (RCT) assessing treatments. We review the existing evidence supporting therapies for patients with ANOCA, with a focus on the treatment of CMD, coronary vasospasm, and myocardial bridging.

Risk factor and lifestyle modification strategies in ANOCA

Lifestyle interventions should be instituted in all patients with ANOCA. However, data are limited. An RCT of 62 women testing multiple lifestyle interventions including intensified risk factor control, a low-calorie diet, and an exercise training program, led to reductions in angina frequency and weight loss but did not increase coronary flow reserve (CFR). Cognitive behavioral therapy can improve angina symptoms and reduce recurrent episodes within the first 3 months of treatment. Meditation can also improve quality of life (QoL) and reduce angina in ANOCA.

Keywords

angina with nonobstructive coronary arteries, coronary microvascular disease, coronary microvascular dysfunction, coronary spasm, epicardial spasm, microvascular angina, microvascular spasm, spasm, treatment, vasospastic angina

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https://doi.org/10.1016/j.jscai.2025.102633

Olga Toleva, Nathaniel R. Smilowitz, Odayme Quesada, Manoj Kesarwani, Michael P. Savage, Megha Prasad, Ailin Barseghian El-Farra, Noa Holoshitz, Jeffrey W. Moses, William F. Fearon, Jennifer A. Tremmel, Bruce Samuels, Timothy D. Henry