ANOCA May Not Be as Risky as Feared: Danish Data

Patients with angina but no obstructive coronary artery disease (ANOCA) managed within Denmark’s health system were no more vulnerable than the general population to experiencing worse outcomes over a 15-year period, according to an age- and sex-matched analysis of national registry data.

The results suggest that ANOCA in and of itself doesn’t raise the risk of MI, only slightly increases the risk of ischemic stroke, and is tied to a slightly lower risk of death.

These findings, though from a population-based study, may carry clinical implications, Kevin K.W. Olesen, MD, PhD (Aarhus University Hospital, Denmark), and colleagues say. As they note in their paper, published recently in JACC: Cardiovascular Interventions, ANOCA is generally thought of as a risky condition that merits close attention.

Speaking with TCTMD, Olesen said that physicians can use the new knowledge to reassure patients by saying, “I know you have some symptoms, you have some chest pain. We’re not quite sure what it is, but in general, you are fine. We will continue on our diagnostic workup, but you’re going to be okay.”

Olesen offered several possible explanations for ANOCA’s lack of impact on hard outcomes. For one thing, it may speak to the high quality of care delivered—for free—by the taxpayer-supported Danish health system, something he acknowledged may limit the results’ generalizability. Moreover, with the advent of CT angiography as a means to investigate chest pain, patients are diagnosed earlier in the disease course and treated accordingly.

“We also know that these patients are very keen at seeking their healthcare providers. They go to their GPs when they have their symptoms, and they have a lot of contact with the healthcare system. That might also influence what we are seeing,” he suggested.

Andreas Seitz, MD, and Peter Ong, MD (both from Robert Bosch Hospital, Stuttgart, Germany), in an accompanying editorial, highlight the fact that ANOCA isn’t one entity, but rather an “umbrella term covering various pathomechanisms of angina.” Unfortunately, these registry data aren’t granular enough to tease out mechanism, they note.

That said, this “timely and large-scale analysis” provides novel insights from a population perspective by challenging the “notion that ANOCA uniformly portends elevated cardiovascular risk, instead confirming age- and sex-dependent risk differences and a potential impact of contemporary preventive care in patients with ANOCA,” they write.

MI, Stroke, and Death

For the cohort study, the researchers turned to the Danish National Patient Registry to identify 21,132 patients who were suspected of having stable angina but found to have no or mild CAD on angiography from 2003 to 2021. These patients were matched 1:5 by age and sex to 105,660 individuals from the general population without known CAD. Median follow-up duration was 10.7 years, median age was 62 years, and 44.9% were male.

Compared with the general population, the ANOCA patients were more apt to have diabetes, hypertension, chronic pulmonary disease, heart failure, and atrial fibrillation. They also were more likely to receive antithrombotic agents, statins, antihypertensive drugs, and glucose-lowering drugs.

At 15 years, there was no significant between-group difference in the cumulative incidence of MI. Ischemic stroke was slightly more common and death slightly less common for ANOCA patients compared with the general population. The most frequent causes of death were cancer and cardiovascular disease.

Sex-, Age-Matched Comparison: 15-Year Outcomes

The lowest risks seen among ANOCA patients versus the general population were seen for men and those at least 75 years old. Notably, ANOCA patients younger than 55 years had higher incidence of all three endpoints compared with the general population.

The researchers note that their dataset did not have sufficient information to take a deeper dive into the various mechanisms that can drive ANOCA.

Among the study’s “most interesting points,” said Olesen, are the age-dependent risk differences. “Let’s say you’re 80 years old, you come [in for] the angiography, you have completely normal vessels. I think [clinicians] could perhaps look at the risk profile of the patient and maybe you might even have to de-escalate some kinds of treatment,” he said.

For a young adult, “I would still be quite focused and following this patient” with an eye toward prevention, he said. “If they have any potential risk factors, still continue to treat them as aggressively as you would [have] before and  [don’t] look too much at what’s going on with the angiography,  because they will have many, many decades to potentially develop disease.”

Prior studies have investigated strategies for clarifying an individual patient’s ANOCA phenotype and tailoring care based on that knowledge.

The editorialists say it’s important to keep the condition’s heterogeneous nature in mind. “Some ANOCA subpopulations (ie, patients with microvascular disease) should continuously be considered at higher risk for cardiovascular events, while other subpopulations (ie, patients with coronary spasm) may be considered rather low-risk patients,” Seitz and Ong advise.

With the study’s signal that younger people with ANOCA may be potentially more at risk, they say that clinicians should continue to comprehensively investigate patients’ coronary physiology and offer personalized risk assessment and treatment. Even if this tailored care doesn’t impact hard outcomes, it could prove beneficial for quality of life, as seen in the ILIAS ANOCA trial.

In Denmark, said Olesen, clinicians increasingly have moved towards a different tactic: treating each patient’s symptoms to see if they respond before deciding whether to conduct more-intensive tests. The rationale is that this “doesn’t really provide anything additional of interest for us, because it doesn’t really change how we would treat these patients,” he explained, noting that this often involves first trying calcium channel blockers or beta-blockers. Also, “I would look at other organ systems that could potentially contribute to the symptoms.”

The investigators, as a next step, are hoping to pursue a similarly structured analysis of registry data that includes coronary CT scans in addition to angiography, Olesen reported.