The Warrior study found no effect of intensive therapy on cardiac events in women

The Warrior study found no effect of intensive therapy on cardiac events in women

An intensive three-drug regimen of cardiac medications did not significantly affect the rate of major cardiovascular events in women who experienced signs and symptoms of ischemia or had insufficient heart muscle but no blockages, according to research presented at the American Cardiology Annual Scientific Session (ACC.25).

In the United States, an estimated 4 to 5 million women visit hospitals and clinicians each year reporting signs of reduced blood flow to the heart, such as: About half of these women do not have obstructive coronary artery disease (CAD).

In this first large, randomized controlled trial in women without obstructive CAD, called Warrior, researchers compared intensive medical therapy with usual care.

Obstructive CAD occurs when a plaque buildup narrows or partially blocks the heart's arteries. It is a major driver of heart attacks, heart failure and other serious heart problems. Even without obstructive CAD, people who experience signs and symptoms of ischemia may experience reduced quality of life and increased risk of major cardiac events. Several small studies have suggested that these patients may benefit from cardiac medications such as statins, low-dose aspirin and angiotensin converting enzyme (ACE), or ARB (ARB) inhibitors (ACE).

This condition is very common and is the common reason for an unplanned visit to a primary care provider or emergency room among women. It is an important societal burden in terms of cardiovascular outcomes, quality of life, and healthcare costs and resources. “

Carl J. Pepine, MD, professor of medicine at the University of Florida and the study's principal investigator

The study included 2,476 women at 71 medical centers in the United States. 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 such as hypertension (high blood pressure), high-density lipoprotein cholesterol, or a family history of CAD.

Patients were randomly assigned to receive intensive medical therapy consisting of a high-intensity statin, an ACE inhibitor or ARB at the maximum tolerated dose, and a low-dose aspirin. The other half received usual care, meaning decisions about prescriptions or other treatments were left to the treating doctor's discretion.

There was no significant difference between groups in the study's primary endpoint, a composite of 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 approximately 16% of patients in both study arms. There were also no differences observed between intensive medical therapy and usual care for any secondary outcomes or subgroups analyzed.

An important aspect of the study is that about half of the patients randomized to usual care ended up being prescribed the same medications as those assigned to intensive medical therapy, meaning that a large proportion of patients in the control arm received a treatment regimen that was similar to patients in the intervention arm. In addition, many participants were already taking one or more of the study medications before enrolling in the study. 70% stopped taking statins, with about half taking an ACE inhibitor or ARB and 40% taking beta-blockers at baseline.

"The study highlights the diagnostic and treatment confusion in this condition. For example, clinicians at some sites were more concerned that these women were on statins," Pepine said.

While the trial doesn't move the needle in terms of informing guidelines, the researchers said it provides valuable insight into drug feasibility and tolerability, adherence and prescribing practices that may help inform future studies on the optimal treatment of women with evidence of ischemia without CAD.

The researchers also said the study was negatively impacted by the Covid-19 pandemic. All study activities were paused for approximately six months at the start of the pandemic and at some sites activities did not resume due to staffing limitations. As a result, the trial fell short of its goal of enrolling 4,422 participants.

"We do not consider this a definitive effort at this point; nevertheless, it is informative for the field," Pepine said. "We also expect that secondary analyzes and ancillary studies will provide important information about the pathophysiology and treatment of this condition. Future studies can start from an enlightened position."

Several ancillary studies will examine both quality of life and cardiovascular outcomes using AI-enabled coronary analysis in patients undergoing CT-CT angiogram to define coronary anatomy for inclusion in the study. In addition, the Warrior Biorepository collected blood samples from study participants that will be used to study disease mechanisms and possible new therapeutic targets. The researchers plan to continue these side studies to ensure further insights.

The study was funded by the US Department of Defense.

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