Coronary Interventional Trials Featured at ACC.26

Late-breaking clinical trials presented at ACC.26 focusing on coronary interventions included several looking at intravascular guidance in complex, high-risk procedures (IVUS-CHIP), bifurcation lesions (DKCRUSH VIII), and unprotected left main PCI (OPTIMAL). The STEMI Door-to-Unload (STEMI-DTU) trial investigated primary left ventricular (LV) unloading in patients with anterior STEMI without cardiogenic shock.

IVUS-CHIP: IVUS-Guided PCI Not Superior to Angiography-Guided Complex High-Risk PCI  

IVUS imaging has been recommended to optimize PCI, specifically to guide PCI strategy and stent optimization. Data have supported its use in complex disease due to a higher risk of target vessel failure (TVF), yet uptake and adoption of IVUS varies between and within countries, which may reflect lack of standards for stent optimization or heavy reliance on angiography.

The IVUS-CHIP (n=2,020) open-label, randomized, event-driven, controlled European trial compared IVUS-guided PCI (using prescriptive stent-optimization criteria) to angiography-guided PCI on the primary composite endpoint of TVF, comprised of cardiac death, target vessel myocardial infarction (TVMI), or clinically driven target vessel revascularization (TVR).¹ Patients with stable angina or unstable angina (UA)/non–ST-segment elevation MI (NSTEMI) and complex (i.e., severe calcification, ostial, bifurcations, left main [LM], chronic occlusion, long lesions, or in-stent restenosis) lesions were enrolled. Dual antiplatelet therapy post-PCI was recommended, as per guidelines.

At a median follow-up of 19 months, the primary endpoint occurred in 13.9% in the IVUS-guided PCI group vs. 11.1% in the angiography-guided PCI group (hazard ratio [HR], 1.25; 95% CI, 0.97-1.60; p=0.08). Individual primary and key secondary endpoint events were also higher in the IVUS-guided PCI compared with the angiography-guided PCI group. These findings differ from the RENOVATE-COMPLEX-PCI trial, which found lower rates of TVF with intravascular imaging-guided PCI vs. angiography-guided PCI, although several trial-level differences merit consideration.²

IVUS-CHIP prespecified stent optimization criteria were achieved less often (48.0% vs. 55.5%), had greater distal stent edge plaque burden, and had high rates of post-dilatation (84.5%) in the control (angiography-guided PCI) arm. Lower than initially estimated event rates in the angiography-guided PCI arm of IVUS-CHIP may have influenced power. Both IVUS-CHIP and RENOVATE-COMPLEX PCI trials showed lower rates of stent thrombosis with an IVUS-guided PCI strategy.

Although primarily hypothesis generating, whether an IVUS-guided PCI approach may have advantages based on achievement of specific stent optimization ranges, target lesion subsets, or patient-specific characteristics (~21% of trial participants were women) remains to be explored.

OPTIMAL: IVUS-Guided PCI Not Superior to Angiography-Guided PCI in ULMCAD

Continuing the theme of IVUS-guided PCI vs. angiography-guided PCI, the OPTIMAL trial tested whether the IVUS-guided PCI approach (n=401) was superior to the angiography-guided approach (n=405) in patients with significant unprotected LM coronary artery disease (ULMCAD).³ Patients were eligible if they had stable angina or UA/NSTEMI and ≥50% diameter stenosis of ULMCAD with moderate/severe ischemia on noninvasive testing or had ischemic symptoms despite medical therapy. In the IVUS-guided PCI group, pre-PCI IVUS was strongly recommended, whereas post-PCI IVUS was mandatory to accomplish stent optimization recommendations.

The primary composite endpoint of stroke, MI, revascularization, or death occurred in 33.7% in the IVUS-guided PCI group vs. 30.9% in the angiography-guided PCI group (HR, 1.11; 95% CI, 0.87-1.42; p=0.40) at a median follow-up of 2.9 years. Other secondary endpoints at the device or vessel level were also similar between groups.

Despite strong endorsement from practice guidelines to use IVUS guidance for ULMCAD PCI, the OPTIMAL trial did not show superiority of an IVUS-guided PCI approach over the control arm of angiography-guided PCI. Estimated event rates in the trial were sufficient, anatomical complexity scores were high (mean SYNTAX score, 29.7), and 49.2% of patients presented with acute coronary syndrome. However, both groups also had very high rates of both post-dilatation (97.0% IVUS group; 96.0% angiography group) and proximal optimization (89.6% IVUS group; 85.1% angiography group).

Application of trial results to women (only 21.6% enrolled) who may have smaller vessels, all-comers with ULMCAD, PCI treatment after atheroablation (only 8.2% received rotablation), and whether operator experience level may be an effect modifier in IVUS vs. no-IVUS in ULMCAD PCI remain to be explored. Thus, the OPTIMAL findings may temper existing recommendations for routine use of IVUS in ULMCAD PCI.

DKCRUSH VIII: IVUS-Guided PCI Is Superior to Angiography-Guided PCI in Treatment of CBLs

Treatment of coronary bifurcation lesions (CBLs) with PCI may involve a single stent, with provisional treatment of the side branch, or an upfront two-stent approach. As large side branches develop severe disease with greater disease length, concern regarding side branch loss during PCI shifts operators towards adoption of two-stent strategies. Although many iterations of these techniques exist, the double-kissing (DK) crush technique has been compared in clinical trials against provisional and some two-stent approaches and has shown favorable outcomes, albeit among expert operators.

Whether IVUS-guided PCI compared with angiography-guided PCI while implementing the DK crush technique results in better outcomes in complex CBLs was evaluated in the DKCRUSH VIII trial.⁴ DKCRUSH VIII was a randomized, open-label, superiority trial conducted in 24 centers in China by operators who had previously performed ≥20 DK crush PCIs and compared IVUS-guided PCI to angiography-guided PCI with respect to the occurrence of the primary endpoint of TVF (cardiac death, TVMI, or clinically driven TVR) at one year.

Angiographic follow-up was performed at 13 months, with IVUS follow-up in the IVUS assigned group. Complexity was defined using criteria from DEFINITION, which has previously established CBL risk with different stenting approaches.⁵

In those randomized to IVUS-guided PCI, there was mandatory pre-PCI, intraprocedural PCI, and post-PCI assessment to encompass sizing, rewiring assessment, and stent apposition and optimization. Specific optimization criteria in both non-LM and LM CBL were outlined. Most patients presented with an acute coronary syndrome, and distal LM bifurcation was treated in 44.3% of participants.

Patients in the IVUS-guided PCI group (n=277) experienced a significantly lower rate of the primary outcome event compared with patients in the angiography-guided PCI group (n=278) (6.1% vs. 14.7%), respectively; HR, 0.40; 95% CI, 0.23-0.71; p=0.002). The IVUS-guided PCI group also had lower rates of spontaneous MI at 30 days compared with the angiography-guided PCI group (0.4% vs. 2.9%), including 63% reduction in clinically driven TVR and 55% reduction in TVMI. There were no between-group differences in either total mortality or cardiac mortality.

Notably, only one-quarter of patients were women, calcified bifurcations requiring atherectomy were excluded, and non-DK crush techniques were not represented. Notwithstanding, the ability to achieve optimal post-PCI IVUS criteria in three of four cases underlies the meticulous approach by the investigators, the important role of IVUS guidance for complex stenting techniques (e.g., DK crush) in complex CBLs, and the observed clinical benefits of IVUS-guided PCI in the DKCRUSH VIII trial.

STEMI-DTU: LV Loading Does Not Reduce Infarct Size in Patients With Anterior STEMI

Despite primary PCI for STEMI, a substantial proportion of patients suffer large infarctions, heart failure, and early mortality. Whether early mechanical LV unloading to reduce wall stress and afterload followed by primary PCI reduces infarct size compared with no unloading and primary PCI was tested in the STEMI-DTU trial.⁶

STEMI-DTU was an open-label, multicenter, randomized clinical trial that assigned patients with anterior STEMI within six hours of symptom onset to LV unloading with a transvalvular micro-axial flow pump (TV-mAFP) for 30 minutes prior to performing primary PCI (n=262; LV unloading group) vs. primary PCI without LV unloading (n=265; control group).

The TV-mAFP group had femoral angiograms to confirm suitability for device placement, LV pressures recorded, and left ventriculography. TV-mAFP was maintained at the highest support level without causing suction and continued for ≥4 hours. Coronary angiography and primary PCI were initiated ≤30 minutes after initiation of LV unloading. Bailout PCI in the LV unloading group was permitted for clinical deterioration, but no patients required bailout primary PCI in the treatment group.

The primary outcome was infarct size (IS) expressed as a percentage of LV mass (IS/LVM) as determined by cardiac MRI 3-5 days after primary PCI. There was no significant difference in IS/LVM between the LV unloading group vs. the control group (30.8 ± 16.2% vs. 31.9 ± 16.9%, respectively; mean difference, -1.1%; 95% CI, -4.2% to 2.0%; p=0.50).

At 30 days, the secondary powered safety endpoint was assessed in 260 patients in the LV unloading group who had an attempt at TV-mAFP insertion and demonstrated treatment-related major bleeding (BARC types 3-5) or major vascular complication at a rate of 30.8% (compared with a prespecified performance goal of 26.5%). All major bleeding was access site related and most vascular complications were femoral hematomas. Exploratory secondary endpoints of 30-day and one-year total mortality and cardiovascular mortality were not significantly different between groups.

In STEMI-DTU, the combination of initial TV-mAFP followed by delayed primary PCI did not reduce IS/LVM in patients with anterior STEMI without cardiogenic shock and was associated with higher rates of bleeding complications compared with upfront primary PCI alone.

Several contextual elements of STEMI-DTU deserve acknowledgment: Protocol adherence was high, TIMI 0/1 flow prior to primary PCI was less frequent in the LV unloading group, and the trial represents a meaningful translation of earlier proof-of-concept and preclinical work into a randomized design. The observation that the protocol-mandated waiting period in the treatment arm was associated with longer ischemic time was expected, yet relative IS/LVM remained similar between groups, which requires further understanding of factors influencing ischemia reperfusion injury.

Further studies are needed to provide clarity on the role of LV unloading to reduce IS and outcomes; STEMI-DTU did not find benefit and demonstrated more bleeding for upfront placement of TV-mAFP with primary PCI delay in anterior STEMI without cardiogenic shock.

Future Considerations

Both important lessons and valuable questions can be elucidated from these clinical trials. The mere application of intracoronary imaging technology such as IVUS is unlikely to impact outcomes without correctly pairing important knowledge gained from intracoronary plaque composition and distribution with a therapeutic intervention.

Beyond stent implantation, determining the practicality of achieving specific optimization targets in complex lesions while navigating the challenges of poor image quality, obliquity, or resistant lesions that do not yield to optimization remain important areas of investigation. The additional time, cost, catheter manipulations, and potential risk of complications with IVUS must also be considered. Expert operators and clinical investigators may introduce inherent biases,¹ which may impact generalizability, such as previous knowledge correlating angiographic disease with IVUS findings, but also influence rates of procedural success or safety events, such as bleeding from large bore access.

Unlike typical randomized clinical drug trials, which are usually not subject to confounding based on technical proficiency of clinicians, trials such as IVUS-CHIP, OPTIMAL, DKCRUSH VIII, and STEMI-DTU share a roster of expert operators and investigators. Future analyses may shed light on important concepts related to volume-outcome relationship among individual trials, patient and lesion characteristic differences, and hypothesis-generating findings that drive future investigations to improve patient care and outcomes.

References

1. Diletti R, Daemen J, Faurie B, et al. Intravascular ultrasound-guided or angiography-guided complex high-risk PCI. N Engl J Med. Published online March 30, 2026. doi:10.1056/NEJMoa2601521
2. Lee JM, Choi KH, Song YB, et al. Intravascular imaging-guided or angiography-guided complex PCI. N Engl J Med. 2023;388(18):1668-1679. doi:10.1056/NEJMoa2216607
3. Testa L, De la Torre Hernandez JM, De Maria GL, et al. IVUS-guided versus angiography-guided PCI in unprotected left main coronary disease. N Engl J Med. Published online March 30, 2026. doi:10.1056/NEJMoa2600440
4. Gao X, Kan J, Chen Y, et al. IVUS or angiography guidance for percutaneous coronary intervention in complex coronary bifurcation lesions: the DKCRUSH VIII randomized clinical trial. J Am Coll Cardiol. Published online March 30, 2026. doi:10.1016/j.jacc.2026.01.081
5. Chen SL, Sheiban I, Xu B, et al. Impact of the complexity of bifurcation lesions treated with drug-eluting stents: the DEFINITION study (Definitions and impact of complEx biFurcation lesIons on clinical outcomes after percutaNeous coronary IntervenTIOn using drug-eluting steNts). JACC Cardiovasc Interv. 2014;7(11):1266-1276. doi:10.1016/j.jcin.2014.04.026
6. Kapur NK, Mangner N, Aghili N, et al. Left ventricular unloading in anterior STEMI without shock: the STEMI Door to Unload (DTU) randomized controlled trial. J Am Coll Cardiol. Published online March 28, 2026. doi:10.1016/j.jacc.2026.03.071