Intensive medical therapy did not significantly impact the rate of serious cardiovascular events at five years in women with suspected ischemia with nonobstructive coronary arteries (INOCA), according to researchers presenting findings from WARRIOR during a Late-Breaking Clinical Trial session at ACC.25 in Chicago.

The trial enrolled 2,476 women at 71 medical centers in the U.S. The average age of participants was 60 years and almost 90% of participants were White. Most participants were postmenopausal, about half had obesity and most had other cardiovascular risk factors like hypertension, high LDL-C or a family history of coronary artery disease (CAD).

Researchers randomized participants to receive either intensive medical therapy consisting of low-dose aspirin, a high intensity statin and an ACE inhibitor/ARB or usual care. Treatment for those in the usual care group was left to the discretion of the treating physician.

Overall results found no significant difference between the two groups in terms of the study's primary endpoint, a composite of the first occurrence of death, nonfatal myocardial infarction, nonfatal stroke or transient ischemic attack, or hospitalization for heart failure or angina. At five years, this composite endpoint had occurred in about 16% of patients in both study arms. There were also no differences observed between intensive medical therapy and usual care for any secondary endpoints or subgroups that were analyzed.

According to the researchers, the trial was negatively impacted by the COVID-19 pandemic and fell short of its goal of enrolling 4,422 participants. All study activities were paused for about six months in the early part of the pandemic, with some sites unable to resume activities due to staffing limitations post pandemic. Additionally, another limitation of the study, was that roughly half of the women who were randomized to usual care were ultimately prescribed a treatment regimen similar to those receiving intensive medical therapy. In addition, many participants were already taking one or more of the study drugs before enrolling in the study, with 70% taking statins, about half taking an ACE inhibitor or ARB and 40% taking beta-blockers at baseline.

Despite the study's limitations, Eileen Handberg, PhD, FACC, said that WARRIOR should not be considered a negative trial, nor should the findings be interpreted as endorsing discontinuation of statin and ACE inhibitor/ARB medications among women with cardiovascular risk factors. While the trial does not move the needle in terms of informing guidelines, she noted that it does provide valuable insights on feasibility and medication tolerability, adherence and prescribing practices that can help to inform future trials on the optimal treatment for women experiencing signs of ischemia without CAD.

"We do not consider this to be a definitive trial at this point; however, it is nevertheless informative for the field," said Carl J. Pepine, MD, MACC, the study's principal investigator. "The trial demonstrates the diagnostic and treatment confusion around this condition; for example, clinicians at some sites felt more strongly about these women being on statins. … We also expect that secondary analyses and ancillary studies will yield important information on the pathophysiology and treatment of this condition. Future trials can move forward from an enlightened position."

Clinical Topics: Atherosclerotic Disease (CAD/PAD)

Keywords: ACC Annual Scientific Session, ACC25, Coronary Artery Disease