Dig Deeper When Dealing With Nonobstructive CAD, AHA Urges

Extra scrutiny is warranted to identify the underlying causes of chest pain in patients with nonobstructive coronary disease (NOCA), urges a new scientific statement from the American Heart Association (AHA). The report outlines available evidence with the idea of helping clinicians know their options when it comes to testing and treatment.

Leandro Slipczuk, MD, PhD (Montefiore Medical Center, Bronx, NY), who served as vice chair of the writing committee, elaborated on why this topic is timely.

“Cardiology is undergoing a transition now from a pure focus on identifying patients with obstructive CAD and treating them aggressively, [sometimes] after they’ve had an MI, to moving sooner [due to] realizing that nonobstructive CAD is not benign—and that it is heterogeneous and that it is common and undertreated,” he told TCTMD.

Slipczuk and colleagues, in their statement, point out that following the endorsement of CT angiography in the 2021 US chest pain guidelines, a rising number of individuals experiencing angina are found to have NOCA.

“In addition, recent advances in artificial intelligence solutions, hardware, and software have allowed identification of microvascular disease and introduced new risk categories within nonobstructive CAD with a risk continuum between primary and secondary prevention,” they note.

Several recently presented trials have explored the best strategies for diagnosis and treatment of patients with nonobstructive CAD: PROMISE, released at TCT 2025, looked at those with myocardial infarction, and CorCMR, released at the AHA 2025 Scientific Sessions, focused on those with angina. Another trial from the AHA meeting, VESALIUS-CV, approached a different angle by showing the PCSK9 inhibitor evolocumab (Repatha; Amgen) could reduce major adverse cardiovascular events even in high-risk patients who’d yet to experience one.

Slipczuk noted that people with NOCA are often told, “You don’t have obstructive CAD,” after which “nothing else gets done” to address their condition. “We’re trying to break that inertia,” he added.

There’s growing recognition within cardiology that it’s important for clinicians to address disease before an event happens, he said.  “It’s too expensive to have people go into heart failure or have a heart attack. It’s too expensive from the financial standpoint [and] the loss of quality of life and the impact on patients—we’re too late.”

This statement isn’t a formal guideline but rather is meant to clarify “what data is there, what gaps are in the data, and what needs to be done in the future to provide the best interaction between preventive therapies and the information we have from invasive and noninvasive imaging,” said Slipczuk.

For clinicians in everyday practice, the process of managing patients with NOCA starts—but doesn’t end—with diagnosis, Slipczuk commented. “Just telling someone to eat healthy and starting a statin is not enough. There’s a lot more out there now.”

Angina, Ischemia, MI, and More

Nonobstructive CAD is not one entity, as the scientific statement makes clear. Among the various presentations are angina with nonobstructive coronary arteries (ANOCA), myocardial infarction with nonobstructive arteries (MINOCA), and ischemia with nonobstructive arteries (INOCA), not to mention self-resolving noncardiac chest pain. Pathogenesis varies from plaque disruption to spontaneous coronary artery dissection, epicardial coronary artery vasospasm, coronary embolism, being in a hypercoagulable state, microvascular disfunction, and supply-demand mismatch.

An accurate diagnosis importantly allows for targeted treatment, the authors say. “Recognizing that risk is a spectrum, we define stages with the goal of improving utilization of more aggressive preventive therapies in those at the highest risk of the spectrum.”

Numerous tools—CT angiography, calcium scoring, IVUS, OCT, MRI, and PET—can be used to gauge an individual patient’s risk level based on plaque characteristics. In addition, “physiologic testing to determine the significance of a coronary stenosis or for coronary microvascular disease assessment is an important tool to guide management in patients with suspected ischemic symptoms or evidence of ischemia on noninvasive stress testing who are found to have NOCA on coronary angiography,” Slipczuk et al advise.

The scientific statement lays out four stages of NOCA, ranging from Stage 0 to Stage 3, with therapies tailored accordingly. At the lower end of the spectrum, lifestyle modification may be sufficient, but as risk rises, statins and “emerging therapies” such as PCSK9 inhibitors, colchicine, and others may be helpful. Depending on the scenario, other options for medical therapy include antiplatelet and anticoagulant drugs, cardiometabolic medications (glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors), antihypertensives, beta-blockers, and ACE inhibitors/ARBs.

“The current proposal for individualizing therapy intensification according to risk stages and patient characteristics presents a promising approach to address the heterogeneity of risk within NOCA,” the authors assert. This approach is now being tested in the TRANSFORM trial.

Moving forward, they say, “wider adoption of and reimbursement for [coronary artery calcium] assessment, new plaque-guided treatment RCTs, and responsible deployment of AI solutions are warranted.”