Less Plaque With Intensive Medical Therapy vs Usual Care in INOCA: WARRIOR

MONTREAL, Canada—Intensive medical therapy (IMT) bests usual care for reducing noncalcified coronary plaque in women who have ischemia with nonobstructive coronary arteries (INOCA), according to results of a serial imaging subanalysis of the WARRIOR trial.

The new data, presented by Joel Lenell, MD, PhD (Cedars-Sinai Medical Center, Los Angeles, CA), recently at the 2025 Society of Cardiovascular Computed Tomography (SCCT) meeting, showed that IMT led to significant reductions in both LDL cholesterol and noncalcified plaque over 2 years when compared with usual care in a subset of patients who underwent repeat coronary CT angiography (CCTA).

In WARRIOR, the intensive treatment regimen—one that included a high-intensity statin, an ACE inhibitor or ARB at the maximally tolerated dose, and low-dose aspirin—failed to reduce the risk of cardiovascular events at 5 years when compared with a strategy of usual care. The trial left many scratching their heads as to how best treat INOCA patients, but investigators say the new CCTA analysis suggests the more intensive strategy appears to be working.

“This study offers evidence in support of a medical treatment intervention to control plaque progression among women with suspected INOCA,” Lenell said during the SCCT session. “It offers a description of early plaque changes under intensive medical treatment that may precede differences in long-term outcomes within the main trial.”

The larger reduction in noncalcific plaque, which is unstable and prone to rupture, suggests that IMT results in greater plaque stabilization than usual care, say researchers. “I think it’s a relief in a way that we can modulate this disease process and have something to offer these patients,” Lenell told TCTMD.

Session co-chair Maros Ferencik, MD, PhD (Oregon Health & Science University, Portland), said the findings confirm “that plaque morphology or composition is changing in a positive way when you’re intervening.”

‘Small Difference, But It Is There’

The study included 186 patients enrolled in WARRIOR who were randomized to IMT (n = 94; mean age 62 years) or usual care (n = 92; mean age 60 years) and who underwent serial CCTA scanning with good image quality at baseline and then at least 2 years after randomization. All patients had atherosclerotic plaque with no differences in plaque characteristics. Prior to randomization, baseline medication use between the IMT and usual-care groups was well balanced, with about 60% on statins, 40% on ACE inhibitors or ARBs, and just over half on aspirin.

At both 24 and 36 months, patients in the IMT arm had significantly lower LDL cholesterol levels compared with those in the usual care arm (P = 0.018). Systolic BP was lower for those treated with IMT at 24 months, but this was not sustained at 36 months.

The researchers saw a significantly larger reduction in noncalcified plaque in the IMT arm compared with usual care between the first and second CCTA scans (P = 0.003 for difference). Additionally, there was a significantly higher increase in the volume of calcified plaque in the IMT vs usual-care groups (P = 0.013).

On multivariate analysis, IMT was an independent predictor of lower noncalcified plaque volume over time (P = 0.027), as was index total plaque volume (P = 0.002). Oppositely, index pericoronary adipose tissue (PCAT) attenuation was associated with higher noncalcified plaque volume (P = 0.003).

While the overall findings were not unexpected to the researchers, senior investigator Damini Dey, MD (Cedars-Sinai Medical Center), told TCTMD they were “surprised that the groups were so well matched.” In the main trial, the high use of statins and ACE inhibitors/ARBs in the usual-care arm was hypothesized as the reason why IMT did not reduce the risk of cardiovascular events.

The high baseline levels of statin use across the board set a tall bar for showing the additional benefit of IMT over time in terms of plaque regression and stabilization. “But the difference was there,” she said. “It’s a small difference, but it is there. So, it’s promising.”

According to Lenell, the next steps include looking at symptom relief and clinical outcomes over the long term “and to do that preferably in a less-balanced population in terms of treatment between the two arms so we really can evaluate the effect of this intensive medical treatment regimen.”

Kavitha Chinnaiyan, MD (Corewell Health, Royal Oak, MI), session-co chair and SCCT president, highlighted that women present a particular challenge. “We can change plaque with the medical therapy, but then what does this mean for the patient with regard to downstream outcomes and how they feel and their symptoms and their quality of life? That, I think, is the question that remains unanswered.”

Dey commented that another study to be presented at the upcoming European Society of Cardiology Congress will add more to this conversation as it will show that baseline noncalcified plaque volume and burden have strong correlations with the Seattle Angina Questionnaire “and indeed were predictors of weekly angina in women.”