Women presenting with angina and suspected ischemia frequently have no obstructive coronary artery disease, referred to as angina with non-obstructive coronary arteries (ANOCA) or ischemia with non-obstructive coronary arteries (INOCA). The role of intensive medical treatment (IMT) in improving outcomes in this population remains uncertain.

This randomized, prospective trial with blinded-outcomes evaluation, published in Open Heart, assessed whether IMT reduces major adverse cardiovascular events (MACE) in women with suspected ANOCA/INOCA. A total of 2,476 women were enrolled across 71 sites in the United States and randomized to IMT, consisting of high-intensity statin, angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB), and aspirin, or to usual care (UC).

The primary outcome was a composite of all-cause death, myocardial infarction, stroke or transient ischemic attack (TIA), and hospitalization for angina or heart failure. Secondary outcomes included individual components, quality of life, and win ratio.

The study population had a mean age of 64 years, with well-controlled baseline blood pressure and low-density lipoprotein cholesterol, and high background use of statins and ACEi/ARB.

Over a median follow-up of 2.5 years, 421 primary events occurred (221 in IMT vs 200 in UC), with no significant difference between groups (HR 1.13 [95% confidence interval (CI): 0.94 to 1.37; P=0.20]). Secondary outcomes were also similar. Hospitalization for angina was the dominant contributor to MACE. Sensitivity analysis accounting for treatment crossover did not show a significant difference (estimated HR 0.74 [95% CI: 0.352 to 1.558; P=0.43]).

IMT did not reduce MACE in women with suspected ANOCA/INOCA, although limited statistical power precludes ruling out potential benefit. These findings highlight the need for further investigation in this population with a high burden of angina-related hospitalizations and impaired quality of life.