Tirzepatide therapy started before transcatheter aortic valve replacement (TAVR) and continued after the procedure appears to reduce subclinical leaflet thrombosis and paravalvular leak (PVL) in obese patients, according to new study findings. On a Zoom call during a late-breaking clinical trial session at Cardiovascular Research Technologies (CRT) 2026 in Washington, D.C., AM Thirugnanam, MD, from the Ipcard Cardiac Care Center in Hyderabad, India, reported that at six months, hypoattenuated leaflet thickening (HALT) occurred in 8.4% of patients in the tirzepatide arm compared with 21.6% in the control group. This translated to a relative risk of 0.39 (95% confidence interval [CI] 0.21–0.73; p=0.002). Rates of at least mild PVL were also lower in the tirzepatide arm, at 10.7% versus 25.3% with standard care (p=0.006). Mechanisms of action “Tirzepatide therapy initiated pre-TAVR and continued post-procedure significantly reduced subclinical leaflet thrombosis and PVL in obese patients, possibly via anti-inflammatory and metabolic mechanisms,” noted Dr. Thirugnanam. Further findings revealed that the therapy appeared to improve metabolic and inflammatory markers with C-reactive protein (CRP) decreasing 38% in the tirzepatide group versus 10% in controls. Mean weight loss reached 9.2 ± 2.8 kg compared with 1.6 ± 1.2 kg in the standard care arm, with both differences reaching statistical significance (p<0.001 for both). Major adverse valve events favored tirzepatide, occurring in 4.6% of patients versus 8.4% in the control group, although that difference did not reach statistical significance (p=0.18). Major bleeding was low in both groups, at 2.3% and 3.1%, respectively (p=0.61). Multivariable analysis “The TAVR-MET trial provides the first evidence that metabolic modulation can improve bioprosthetic valve healing and hemodynamics in obesity-associated aortic stenosis,” the investigators noted. Multivariable analysis suggested the benefit may be linked to both inflammation reduction and weight loss. Tirzepatide use, a CRP reduction of more than 30%, and achieving a body mass index below 32 kg/m² at six months each independently predicted the absence of HALT. “This late-breaking study suggests tirzepatide may emerge as a novel adjunctive therapy to reduce HALT and PVL following TAVR in obese individuals, supporting a multidisciplinary cardio-metabolic approach,” concluded Dr. Thirugnanam. Study details The study enrolled 260 obese patients across eight high-volume centers, randomly assigning 130 to tirzepatide and 130 to standard care. Patients in the treatment arm received tirzepatide 10 mg once weekly starting four weeks before TAVR and continuing for 12 months after the procedure. All patients received standard antithrombotic therapy in line with guideline-based care. The primary endpoint was the incidence of HALT on 4D-CT or transesophageal echocardiography at six months. Secondary endpoints included at least mild PVL, major adverse valve events, weight reduction, C-reactive protein (CRP) levels and major bleeding. Image Credit: Bailey G. Salimes, CRTonline.org Image Caption: AM Thirugnanam, MD, from the Ipcard Cardiac Care Center in Hyderabad, India, presents his late-breaking clinical trial via Zoom on March 9, 2026, at Cardiovascular Research Technologies (CRT) in Washington, D.C.