The year in thrombosis, CAD: New PCI populations and DAPT strategies
Key takeaways:
- A speaker highlighted key advances in thrombosis and coronary disease treatment in 2024.
- Topics included updated European guidelines for DAPT after PCI and an upcoming trial marrying coronary CT imaging and AI.
Updates in new antiplatelet therapies, new patient populations for PCI and AI to guide CAD staging were among the top developments in thrombosis and coronary disease from 2024.
At the Cardiometabolic Health Congress in October, Deepak L. Bhatt, MD, MPH, director of Mount Sinai Heart, Dr. Valentin Fuster Professor of Cardiovascular Medicine at the Icahn School of Medicine at Mount Sinai and a member of the Healio | Cardiology Today Editorial Board, discussed recent advances in thrombosis coronary disease management and an upcoming trial bringing together AI and coronary CT angiography.
Updates in thrombosis and DAPT
Bhatt began by discussing the 2024 European Society of Cardiology guidelines for the management of chronic coronary syndromes, specifically the updated recommendations for dual antiplatelet therapy duration after PCI.
The guidelines, published in the European Heart Journal, stated that the choice and duration of antithrombotic therapy should be individualized based on patients’ ischemic and bleeding risk.
“The bottom line is that they’re saying in the default pathway, about 6 months of dual antiplatelet therapy after elective PCI. But there are options after that. After the 6 months, the guidelines say you do either aspirin alone or clopidogrel alone, as a class I indication, which means those are the options, one or the other,” Bhatt said. “So it’s a shortening of the duration of DAPT compared with prior recommendations.”
Next, Bhatt discussed the results of the PANTHER meta-analysis that evaluated the use of a P2Y12 inhibitor compared with aspirin monotherapy for secondary prevention of coronary events. The primary endpoint was a composite of CV death, MI and stroke.
The results of PANTHER study, published in the Journal of the American College of Cardiology, showed that across seven different trials, P2Y12 inhibitor monotherapy was associated with lower risk for the primary composite endpoint compared with aspirin monotherapy for secondary prevention (HR = 0.88; 95% CI, 0.79-0.97; P = .012).
Bhatt highlighted the main results of the South Korean EPIC-CAD trial presented at the ESC Congress, which assessed the use of edoxaban monotherapy (Savaysa, Daiichi Sankyo) compared with dual therapy with edoxaban and a single antiplatelet agent in patients with atrial fibrillation, a CHA2DS2-VASc score of 2 or higher and stable CAD. The primary outcome was 1 year net adverse clinical events including all-cause death, stroke, systemic embolic events, MI, urgent revascularization and major or clinically relevant nonmajor bleeding.
As Healio previously reported, edoxaban monotherapy reduced risk for adverse clinical events, mainly driven by lower bleeding risk, for patients with AF and stable coronary disease, compared with DAPT.
Bhatt also provided an overview of the negative results of the phase 3 OCEANIC-AF trial of asundexian (Bayer), a novel factor XIa inhibitor for the prevention of stroke and systemic embolism in patients with AF.
Bayer previously announced in 2023 that the trial was halted due to failure of efficacy.
The results of the phase 3 trial were presented at the ESC Congress.
Read Healio’s coverage of the OCEANIC-AF trial here.
Bhatt then reviewed the positive results of the RAISE trial presented at the International Stroke Conference, which evaluated reteplase (China Resources Angde Biotech Pharma Co.) for improving 90-day disability when administered early after stroke onset.
As Healio previously reported, reteplase was superior compared with alteplase for improving 90-day disability after stroke, despite a higher rate of intracranial bleeding in the reteplase arm and similar mortality.
Bhatt also highlighted the AEGIS II trial that tested the “HDL hypothesis” using the investigational infusion CSL112 (CSL Behring) to increase apolipoprotein A-I levels, increasing cholesterol efflux capacity and potentially improving HDL particles.
As Healio previously reported, the HDL hypothesis was a theory that improving HDL function after MI can stabilize atherosclerotic plaque and reduce risk for future events, according to C. Michael Gibson, MD, MS, interventional cardiologist, CV researcher and CEO of the combined nonprofit Baim and PERFUSE research institutes at Harvard Medical School, who presented the main results of the AEGIS II trial at the 2024 American College of Cardiology Scientific Session.
The results of the trial did not support the HDL hypothesis and the primary outcome of MI, stroke and CV death was not significantly different among patients randomly assigned to CSL112 or placebo.
The year in coronary disease
To discuss recent updates in the treatment of coronary disease, Bhatt highlighted the results of the ORBITA-2 trial, presented at the 2023 American Heart Association Scientific Sessions. The trial evaluated the effects of PCI vs. sham procedure on angina symptoms in patients with stable angina or anginal-equivalent symptoms, evidence of ischemia and severe coronary stenosis receiving little or no antianginal medication.
As Healio previously reported, PCI improved angina symptoms at 12 weeks compared with a sham procedure. Read Healio’s coverage of the ORBITA trials.
For MULTISTARS-AMI, presented at the ESC Congress, researchers assessed PCI of nonculprit lesions during the index procedure for STEMI compared with staged PCI of nonculprit lesions within 19 to 45 days after successful primary PCI, Bhatt said.
The researchers reported that immediate PCI of nonculprit lesions during index hospitalization for STEMI was noninferior, with fewer adverse events compared with staged PCI. Read more.
Bhatt also discussed NOTION-3, presented at the ESC Congress, which evaluated transcatheter aortic valve replacement for aortic stenosis and either PCI or conservative treatment for CAD among patients with severe symptomatic aortic stenosis and at least one coronary artery stenosis with fractional flow reserve of 0.8 or less or stenosis of at least 90%.
In patients with severe aortic stenosis and CAD undergoing TAVR, simultaneous PCI was associated with better outcomes compared with more conservative CAD management. Read more about the results of the NOTION-3 trial.
Next, Bhatt discussed the AGENT IDE trial, which compared a paclitaxel-coated balloon (Agent, Boston Scientific) with an uncoated balloon for treatment of coronary in-stent restenosis.
The results of the AGENT IDE trial were positive enough in favor of the paclitaxel-coated balloon that it served as the subsequent rationale for the FDA approval of the device for the treatment of coronary in-stent restenosis in patients with CAD.
The presentation also featured the results of the PREVENT trial, which assessed preventive PCI plus medical therapy compared with medical therapy alone for treatment of nonflow-limiting vulnerable coronary plaques. The results were presented at the 2024 ACC Scientific Session.
As Healio previously reported, preventive PCI plus optimal medical therapy was superior to optimal medical therapy alone in this patient population.
“There’s several ongoing trials that are examining this issue, which is kind of modestly powered. Maybe when the trials are all done, the data will have an answer to whether we should be stenting lesions prophylactically to prevent heart attacks,” Bhatt said during the presentation. “I am a bit skeptical of this approach, to be totally honest. I think medical therapy and systemic therapy would win over just trying to stent isolated lesions. But still, it’s very interesting.”
A unique study highlighted by Bhatt was the findings from the global HORUS study evaluating the presence of atherosclerosis in ancient mummified humans, the results of which were published in the European Heart Journal.
“Sometimes people say atherosclerosis has just popped up in the past several generations. People are overeating; they’re taking the car everywhere; it’s urbanization and industrialization that’s making us weak and making atherosclerosis occur. But this study found that atherosclerosis has been around for a while,” Bhatt said during the presentation. “Sometimes people say, ‘but if you got mummified, you were rich, powerful, overeating and you had servants and didn’t have physical activity.’ But they looked across different times, places and not in every place in time was mummification reserved for the wealthy. ... There’s a lot of atherosclerosis back then. Even though we think we’re addressing all the risk factors, atherosclerosis is very complex and it probably isn’t going away anytime too soon.”
What’s new in imaging, CT angiography
Bhatt also highlighted several recent studies in CV imaging, the first of which was published in the European Heart Journal and investigated the use of coronary CT angiography for atherosclerosis evaluation and CV risk estimation.
The researchers reported that coronary CT angiography was able to guide risk stratification of patients into CAD stages 0 to 3 based on plaque burden and 10-year CVD risk.
Bhatt added that AI-based imaging strategies may be able to help improve CAD risk staging and guide treatment.
Bhatt provided additional details about the new TRANSFORM trial, which as Healio previously reported, is a randomized controlled trial designed to compared coronary CT angiography and a paired AI algorithm trained to stage coronary plaque burden with usual care for primary CV prevention.
The AI algorithm (Cleerly) previously received FDA breakthrough device designation and was accepted into the FDA’s Total Product Life Cycle Advisory Program Pilot.
“The idea is, if a patient has a lot of plaque, depending on the severity, to intensify the medical therapy in and algorithmic way going beyond what the guidelines recommend. It’s a matter of trying to address residual risks,” Bhatt said during the presentation. “We go from those with stage 0 and just doing what the guidelines say in the investigation arm to, depending on how much plaque they have, throwing the medical ‘kitchen sink’ at them, targeting things like inflammation, more advanced antithrombotic therapy, lower LDL targets, etc.
“The goal ultimately is to convert the prevention of coronary disease to one like mammography and colonoscopy among CT scanning, which has done so well in cancer for patients that actually undergo those tests,” Bhatt said. “Can we do the same thing with coronary artery disease and detect a problem before that heart attack?”
References:
- Gragnano F, et al. J Am Coll Cardiol. 2023;doi:10.1016/j.jacc.2023.04.051.
- Nurmohamed NS, et al. Eur Heart J. 2024;doi:10.1093/eurheartj/ehae190.
- Thompson RC, et al. Eur Heart J. 2024;doi:10.1093/eurheartj/ehae283.
- Vrints C, et al. Eur Heart J. 2024;doi:10.1093/eurheartj/ehae177.
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Bhatt DL. FDA update and late breaking trials. Presented at: Cardiometabolic Health Congress; Oct. 17-19, 2024; Boston.