Intensive vs More Intensive Lipid-Lowering Therapy and Plaque Regression in Statin-Naive Patients: Prespecified Analyses From the FLOWPROMOTE Randomized Clinical Trial

Prior imaging studies (predominantly using intravascular ultrasound) have demonstrated modest plaque regression with lipid-lowering therapy in stable coronary artery disease (CAD).

The effect of initiating intensive lipid-lowering therapy on coronary plaque regression across the entire coronary tree in treatment-naive patients remains uncertain. To report the prespecified secondary imaging end points of the FLOWPROMOTE trial by comparing the effects of intensive vs more intensive lipid-lowering therapy on plaque regression in statin-naive patients with stable CAD and to assess the association between achieved low-density lipoprotein cholesterol (LDL-C) levels and plaque regression.

FLOWPROMOTE was a multicenter randomized clinical trial enrolling statin-naive patients with newly diagnosed stable CAD, defined by a coronary computed tomography angiography (CTA) stenosis greater than 50% and fractional flow reserve CT less than or equal to 0.80. Coronary CTA was performed at baseline and repeated at 9 and 18 months.

Study data were analyzed from February 2025 to January 2026. Patients were randomized to intensive lipid-lowering therapy (atorvastatin 40 mg) or more intensive lipid-lowering therapy (rosuvastatin 40 mg plus ezetimibe 10 mg) for 18 months.

Prespecified secondary end points included changes in total plaque volume (TPV), noncalcified plaque volume (NCPV), and calcified plaque volume (CPV) across all coronary vessels at 9 and 18 months compared with baseline. Prespecified secondary end points included changes in total plaque volume (TPV), noncalcified plaque volume (NCPV), and calcified plaque volume (CPV) across all coronary vessels at 9 and 18 months compared with baseline.

A total of 104 patients (mean [SD] age, 64 [9] years; 82 male [79%]) were included in this analysis, with 52 patients in the intensive group and 52 patients in the more intensive group. LDL-C levels decreased from 119.7 to 69.5 mg/dL (-a clinically meaningful level) with intensive therapy and from 127.4 to 42.5 mg/dL (-65%) with more intensive therapy (between-group P <.001).

At 18 months, both TPV and NCPV decreased in both groups, with significantly greater regression in the more intensive-therapy group. TPV was reduced by -69.8 mm3 (-21.1%) with more intensive therapy vs -39.0 mm3 (-13.6%) with intensive therapy (between-group difference, -30.9 mm3; 95% CI, -57.2 to -4.5 mm3; P =.02), and NCPV was reduced by -82.3 mm3 (-28.2%) vs -53.5 mm3 (-20.0%), respectively (between-group difference, -28.9 mm3; 95% CI, -53.2 to -4.6 mm3; P =.02).

CPV increased similarly in both groups. Regression of TPV occurred in 90% of patients receiving more intensive therapy compared with 76% receiving intensive therapy (47 of 52 [90%] vs 38 of 51 [75%]; P =.05), and regression of NCPV was observed in 98% vs 77% (51 of 52 [98%] vs 39 of 51 [77%]; P =.001).

Lower achieved LDL-C levels were linearly associated with greater regression of TPV and NCPV.

This secondary analysis of the FLOWPROMOTE randomized clinical trial demonstrated that in statin-naive patients with CAD, more intensive lipid-lowering therapy was associated with significantly greater regression of total and noncalcified coronary plaque burden compared with intensive therapy.

The extent of plaque regression was related to achieved LDL-C levels, supporting the potential for partial reversal of coronary atherosclerosis with intensive lipid reduction.