ACC.26 Late-Breaking Clinical Trials — American College of Cardiology 2026

Key Result: FFRangio (AI-based angiography-derived FFR) was noninferior to invasive pressure wire for guiding PCI: 1-year MACE 6.9% vs 7.1% (HR 0.98, noninferiority p=0.0008). First FDA-approved angiography-derived physiology trial in the US.

Key Result: Deferring PCI until after TAVI was noninferior to PCI-first (24% vs 26% composite endpoint, HR 0.89) with significantly less major bleeding (6% vs 15%). Only 11% of deferred patients needed subsequent PCI.

Key Result: Discontinuing beta-blockers in stable post-MI patients without HF or LV dysfunction was noninferior to continuing treatment — first RCT evidence supporting beta-blocker de-escalation in this population.

Key Result: IVUS guidance for DK crush stenting in complex bifurcation lesions — results from 556-patient multicenter Chinese trial presented at ACC.26 and published in JACC.

Key Result: Ultrasound-facilitated catheter-directed fibrinolysis plus anticoagulation reduced the composite of PE-related death, cardiopulmonary decompensation, or symptomatic recurrence by 61% vs anticoagulation alone (4.0% vs 10.3%; RR 0.39, 95% CI 0.20-0.77, P=0.005) with no increase in major bleeding.

Key Result: WATCHMAN FLX LAAC was non-inferior to NOACs for stroke prevention (5.7% vs 4.8% composite CV death/stroke/embolism at 3 years) and statistically superior for safety, with 43% less non-procedural major bleeding (10.9% vs 19.0%). Net clinical benefit favored the device (15.1% vs 21.8%).

Key Result: LV unloading with Impella CP for 30 min before PCI did NOT reduce infarct size vs immediate PCI (30.8% vs 31.9%, NS) in anterior STEMI without shock. Device-related bleeding/vascular complications were significantly higher (34% vs 6%).

Key Result: Evolocumab reduced 3-point MACE by 25% vs placebo in patients with ASCVD or diabetes but no prior MI/stroke (first demonstration of PCSK9 inhibitor benefit in primary prevention). Heart attack risk reduced 36%. LDL-C reduced 55% to median 45 mg/dL.

Key Result: Targeting LDL-C <55 mg/dL vs <70 mg/dL reduced major CV events by 33% at 3 years (6.6% vs 9.7%) in ASCVD patients. CV death/MI/stroke was also significantly lower (2.3% vs 3.6%). First randomized head-to-head comparison of LDL-C targets.

Key Result: Home-delivered DASH groceries reduced systolic BP by 3.4 mm Hg more than grocery stipends (5.7 vs 2.3 mm Hg reduction) and LDL-C by 6.2 mg/dL more (8.0 vs 1.8 mg/dL) in Black adults in food deserts. Benefits did not persist after intervention ended.

Key Result: Tonlamarsen achieved 67% reduction in plasma angiotensinogen (p<0.0001) but did NOT reduce office systolic BP more than single dose at Week 20 (both ~6.7 mmHg, p=0.97). Intriguingly, BP effects persisted after dosing stopped. Phase 2b trial in acute severe hypertension planned.

Key Result: Angiography-based vFFR was noninferior to pressure wire-based FFR for guiding coronary revascularization: identical 1-year MACE rates with shorter procedures, less radiation, and less contrast.

Key Result: CTO PCI significantly reduced angina symptoms vs sham procedure in the first placebo-controlled CTO trial: 31 more angina-free days over 168 days, with improved quality of life scores. No deaths, MIs, or withdrawals.

Key Result: LV unloading with Impella CP during complex PCI did NOT reduce adverse events in severe LV dysfunction (win ratio 0.85, p=0.30) and was associated with HIGHER all-cause mortality (32.6% vs 23.4%, HR 1.54) and CV death (26.7% vs 14.5%).

Key Result: Mavacamten reduced LVOT gradient by 48.0 mmHg more than placebo (p<0.0001) in adolescent oHCM — first positive Phase 3 trial extending mavacamten to patients ages 12-17. Consistent efficacy across all secondary endpoints with favorable safety.

Key Result: Lung impedance-guided therapy reduced HF hospitalizations by 74% and HF mortality by 74% in HFpEF over 3+ years. Clinicians adjusted medications 2x more frequently with earlier intervention at the preclinical stage.

Key Result: Sotatercept significantly reduced pulmonary vascular resistance in HFpEF with CpcPH (0.3 mg/kg: -0.67 Wood units, p=0.004; 0.7 mg/kg: -0.33, p=0.024 vs +0.26 placebo). Time to clinical worsening reduced 82%.

Key Result: Spironolactone did NOT significantly reduce HF hospitalizations or CV death in HFpEF/HFmrEF (12.7 vs 10.8 events per 100 patient-years). Unexpected increase in total hospitalizations, hypotension, and renal dysfunction in the spironolactone group.

Key Result: T-TEER for severe TR reduced the primary endpoint from 35% to 20% at 2 years, with 40% fewer HF hospitalizations (14% vs 23%). No crossover in the control group — first unconfounded long-term T-TEER outcomes.

Key Result: Emboliner was noninferior to Sentinel for 30-day MACCE during TAVR (4.9% vs 5.0%) with the lowest stroke rates in a trial of this size (2% vs 2.1%). Emboliner captured 3x more large debris particles.

Key Result: Transcatheter mVIV reduced death/disabling stroke by 77% vs redo surgery at 1 year (5.3% vs 20.8%, HR 0.23, p=0.005). Zero CV deaths at 30 days with mVIV vs 12.5% with surgery. First randomized comparison of mVIV vs rMVR.

Key Result: Despite dramatic triglyceride reduction (60-64%), olezarsen did NOT reduce noncalcified coronary plaque volume vs placebo at 12 months (p=0.36). Neutral imaging results despite robust lipid changes.

Key Result: Digoxin reduced the composite of death or new/worsening HF by 18% in rheumatic heart disease — first randomized trial of digoxin in RHD. Toxicity was rare (1%) with no related deaths.

Key Result: Late-breaking results from the OPTIMAL trial presented at ACC.26 — published in NEJM.

Key Result: IVUS-guided PCI in complex coronary lesions — results from a landmark European multicenter trial presented at ACC.26 and published in NEJM.

Key Result: Results from the world's largest sirolimus-coated balloon trial in peripheral artery disease (N>1,250) were presented at ACC.26 and published in NEJM.

Key Result: Late-breaking results from the THRIVE Pilot trial presented at ACC.26.