Trials in coronary imaging, transcatheter tricuspid valve interventions, transcatheter aortic valve implantation (TAVI) in small annuli, and further insights from the REVIVED-BCIS2 study are among the top trailed research coming in 2023 in the interventional cardiology space.
This is according to Mirvat Alasnag (King Fahd Armed Forces Hospital, Jeddah, Saudi Arabia), Roxana Mehran (Mount Sinai Hospital, New York, USA) and Suzanne Baron (Lahey Hospital & Medical Center, Burlington, USA) who spoke to Cardiovascular News about the trials they are expecting to have the most impact throughout the year.
Of the major cardiovascular society meetings coming up in 2023, the American College of Cardiology (ACC) annual meeting (4–6 March, New Orleans, USA) is the first out of the gate, with a programme that features several late-breaking trials namechecked by both Mehran, Alasnag and Baron.
Mehran highlights the release of results from the TRILUMINATE pivotal trial, the first major randomised trial evaluating the safety and efficacy of transcatheter tricuspid valve edge-to-edge repair (TEER) for severe tricuspid regurgitation (TR) as one to watch at the meeting. Trials in tricuspid interventions are of “pivotal” importance, Mehran comments, after significant previous focus has been placed on the aortic and mitral valves in the past. “New technologies are emerging that could take care of tricuspid valve regurgitation”, Mehran observed of the field in general.
TRILIMINATE is exploring the use of the Triclip (Abbott) system in patients in North America and Canada, and Mehran commented that this “incredibly important” study, which is to be presented during a late-breaking trial session on day one of the ACC meeting, may possibly help to “improve and enhance” patient quality-of-life, as well as benefitting clinical outcomes, if early experience with the device is borne out in a randomised trial setting.
Another eagerly anticipated presentation at ACC 2023 will shed light on the effect of myocardial viability, percutaneous coronary intervention (PCI) and functional recovery as observed in the REVIVED-BCIS2 trial. The first data from the trial were released at the annual congress of the European Society of Cardiology (ESC 2022; 26–29 August, Barcelona, Spain), showing that PCI did not reduce all-cause mortality or heart failure hospitalisation in patients with severe left ventricular dysfunction and extensive coronary artery disease when compared to optimal medical therapy.
Alasnag recalls that the trial results sparked “intense discussions” at ESC 2022 following their initial presentation, and she said it will be “critical to assess the role of myocardial viability in the context of percutaneous revascularisation and functional recovery including clinical outcomes.”
“Teasing out the role of viability will be essential, particularly as we interpret these results in the context of other trials such as the STICH trial,” Alasnag tells Cardiovascular News.
Similarly, Mehran says that further findings from REVIVED-BCIS2 randomised clinical trial, will produce “enhanced data” on whether myocardial viability has a role in improving clinical outcomes in patients with heart failure due to coronary artery disease who have been treated with the best medical therapy v. PCI. The issue of myocardial viability is “key” in the context of ischaemic heart disease, said Mehran.
Outside of the ACC meeting, Alasnag identifies the RENOVATE-COMPLEX-PCI trial, which is designed to investigate whether PCI under the guidance of intravascular ultrasound (IVUS) or optical coherence tomography (OCT) improves clinical outcomes compared with angiography-guided PCI in patients with complex lesions, as another to watch in 2023.
“This is a prospective, randomised, open label parallel trial where the choice of intravascular imaging devices such as IVUS or OCT are at the operator’s discretion,” explains Alasnag. “Use of intravascular imaging devices is permitted at any step of the PCI (pre-, during, and post-PCI, but intravascular imaging evaluation after stent implantation will be mandatory.”
Discussing a trial which closely corresponds with RENOVATE-COMPLEX-PCI, Baron pinpoints the ILUMIEN IV which similarly seeks to compare outcomes in patients undergoing OCT verses angiography-guided PCT for complex coronary artery disease. “Over the last several years, there has been a growing body of data supporting intravascular imaging, with multiple studies demonstrating significant reductions in major adverse cardiac events, primarily target lesion revascularisation”, Baron describes, however she notes uptake across the US remains “low”.
Expanding on the significance of ILUMIEN IV’s results, Baron believes that if OCT-guided PCI shows “clinical superiority” to angiography alone, it will not only demonstrate the “feasibility” of the technology, but will “reinforce the growing consensus that intravascular imaging should be a mainstay during any PCI procedure.”
With a continued focus on patients with stable coronary artery disease, Alasnag also pinpointed the TARGET trial, which aims to evaluate whether the availability of computed tomography angiography (CTA) and fractional flow reserve-computed tomography (FFR-CT) might effectively optimise the flow of clinical practice of stable chest pain. This is compared against the conventional clinical pathway in decision making, by avoiding the overuse of invasive procedures, reducing total expenditure and improving outcomes.
The randomised, open labelled, prospectively designed trial is running in six Chinese hospitals with 1,200 participants enrolled. Subjects are assigned to either the routine clinically-indicated diagnostic care group or the CTA/CT-FFR care group.
Noting its comparability to recent studies in cardiovascular intervention, Alasnag notes: “[TARGET] would complement results of the previously published FORECAST trial conducted in the UK, where a strategy of FFR-CT compared to usual care of patients with stable chest pain did not lower costs or improve quality-of-life measures.”
Staying in the coronary space, Alasnag highlights the YELLOW III study as one to follow. The study aims to assess the effect of evolocumab on coronary plaque morphology in patients with stable coronary artery disease on maximally tolerated statin therapy. Using multi-modality intravascular imaging, gene expression analysis of peripheral blood mononuclear cells (PBMC) and transcriptomic-based machine learning algorithms, researchers are hoping to uncover the molecular mechanisms responsible for beneficial changes in atherosclerotic lesions of patients treated with evolocumab. This novel study can be ground breaking in understanding plaque morphology changes in the context of molecular changes in patients treated with PCSK9 inhibitors, Mehran noted.
“Continuing our quest to find less invasive management of patients with severe disease, particularly in ageing populations, is incredibly important,” comments Mehran, pinpointing the significance of trials relating to small aortic annulus to herself and others in transcatheter valve space.
Mehran is a co-principal investigator in the SMART trial—Small Annuli Randomized to Self-expanding Evolut or Balloon expandable Sapien devices—alongside global principal investigator Howard Herman (University of Pennsylvania, Pennsylvania, USA) and co-principal investigator Didier Tchétché (Clinique Pasteur Toulouse, Toulouse, France), which is expected to report results later this year. The trial is investigating safety and performance of the self-expanding Evolut (Medtronic) versus the balloon-expandable Sapien (Edwards Lifesciences) TAVI systems in patients with a small aortic annulus and symptomatic severe native aortic stenosis.
“A large majority—up to 90% of these patients—as could be associated with small annulus, are women” Mehran said, concluding the study will be one of the first leading “female dominated” clinical trials.
Comparably, Baron stated that in the incidence of in-stent restenosis (ISR), drug coated coronary balloons (DCB) have been preferred over the addition of another stent layer in patients with long lesions. Set to compare the use of DBCs to standard balloon angioplasty for the treatment of ISR, the fully enrolled AGENT IDE trial will release its results later in 2023.
If the randomised controlled trial can demonstrate the “adequate efficacy and safety” of DCBs, Baron indicated that “the door opens for evaluation of other uses for this technology”, which could include side branches and small diffusely diseased vessels. She maintained: “Since the theory of less metal in the coronaries has always seemed attractive (e.g. bioresorbable stents), DCBs would definitely be a welcome addition in our toolbox to fight progressive coronary artery disease.”
Anticipating many other trials that are “on the horizon” in 2023 as Mehran said, spanning across renal denervation, drug-coated balloons and artificial intelligence (AI), Baron also noting the potential renal denervation technology has in 2023 to treat resistant hypertension, giving health practitioners “tools beyond oral medication” at their disposal.
Reflecting on upcoming trials and results to come this year, Mehran commented “the field is very bright.” She added: “2023 sparks the interest of rebooting clinical trials and forums to reiterate how important evidence-based medicine is to the progression of interventional cardiology.”
“We are moving toward the future. What we have previously learnt and what we are going to learn in 2023, will make a huge impact when treating patients with cardiovascular disease, helping to promote the continued evolution of the interventional cardiology space—to improve health outcomes of our patients in a bigger and better way.”