BRIGHT-4 trial: Bivalirudin cuts 30-day mortality for STEMI patients undergoing PCI compared to heparin

BIVALIRUDIN IS A SAFER AND MORE effective anticoagulant than heparin for treating patients with ST-segment elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI), and can lower the risk of death or major bleeding by 31%.

These are key findings from a new study led by researchers from the Icahn School of Medicine at Mount Sinai (New York, USA). This is the first largescale clinical trial to compare the two anticoagulants most widely used after PCI, and shows bivalirudin given with a two- to four-hour high-dose infusion significantly reduces death, major bleeding, and thrombosis when compared with heparin, the researchers behind the study have said.

The results were presented in a late-breaking clinical trial at the American Heart Association Scientific Sessions (AHA 2022; 5–7 November, Chicago, USA) and published in The Lancet. This work could have broad implications, changing the treatment course for hundreds of thousands of patients across the world who experience a STEMI, the researchers claim.

“For the first time, this study identifies the best and safest treatment course for patients undergoing stenting to treat a STEMI heart attack,” said co-principal investigator Gregg W Stone (Mount Sinai Hospital, New York, USA). “Compared with heparin, bivalirudin plus a short infusion substantially improved the likelihood of surviving a STEMI and reduced the two most feared complications—major bleeding and stent thrombosis.”

In the BRIGHT-4 trial, patients with STEMI underwent primary PCI, which requires anticoagulant therapy.

The most common anticoagulant used during primary PCI is heparin, but its use can lead to ischaemic and haemorrhagic complications. Heparin and bivalirudin have been compared in six prior large randomised trials in patients with STEMI, but in those studies, they were administered with varying regimens and background therapies. This new research evaluates the two most widely used regimens of heparin and bivalirudin, which have never been directly compared with each other in an adequately sized trial.

Stone along with Yaling Han (Shenyang Northern Hospital, Shenyang, China) led a team of researchers to analyse 6,106 patients enrolled in the study across 87 sites in China between February 2019 and April 2022. All underwent primary PCI for STEMI treatment, nearly all with a procedure that used the radial artery in the wrist to target the blocked heart artery. Patients were randomised to receive the two most widely used regimens of heparin and bivalirudin, which prior studies have shown to be the safest and most effective. One group received heparin alone, administered intravenously. The other group received bivalirudin intravenously, followed by a high-dose infusion for two to four hours after

Investigators followed patients for 30 days after the procedure. The primary goal of the study was to compare the occurrence of allcause mortality or major bleeding.

Researchers found that 4.4% of patients treated with heparin died or had a major bleed within 30 days, compared to 3.1% of patients treated with bivalirudin.

Overall, the bivalirudin

Depression increases likelihood of non-adherence to medical therapy post-PCI

Patients with depression are 10–20% less likely to adhere to guideline-directed medical therapy after percutaneous coronary intervention (PCI), research published in JAMA Network Open has shown.

ACCORDING TO MATTHEW E

Lapa (University of Pittsburgh School of Medicine, Pittsburgh, USA) and colleagues, who conducted the research, the recognition of depression among patients undergoing PCI may facilitate targeted interventions to address medical adherence and improve secondary cardiovascular disease prevention.

Lapa et al conducted a retrospective cohort study of patients undergoing PCI from January 2014 to December 2019, using data from the Optum Clinformatics DataMart database. The study team identified a diagnosis of depression as occurring during the 12 months of enrolment prior to PCI, or within six months after the procedure. Medication adherence was assessed with the proportion of days covered (PDC), calculated as the ratio of the number of days a medication is available and the number of follow-up observation days. Twelve-month adherence was categorised as adequate (PDC ≥80% to <90%) or optimal (PDC ≥90%). group had a 31% reduction in the rate of death or major bleeding compared with patients in the heparin group—a highly statistically significant reduction.

A total of 124,443 patients were included in the assessment, with a mean age of 69.3 years, 41,430 of whom (33.3%) were female. Of this population, 20,711 patients (16.6%) had a diagnosis of depression.

The researchers found that those with depression were significantly less likely to obtain adequate 12-month adherence to antiplatelets (odds ratio [OR], 0.80; 95% confidence interval [CI] 0.77–0.85), β-blockers (OR, 0.84; 95 CI, 0.80–0.88), and statins (OR, 0.88; 95% CI, 0.85–0.93) than those without depression. There was no association between depression and adherence to renin-angiotensin-aldosterone system inhibitors (OR, 0.93; 95% CI, 0.85–1).

The researchers then looked at the specific incidence of death alone and major bleeding alone between the groups. They found that deaths were reduced from 3.9% in heparin-treated patients to 3% in bivalirudintreated patients. Severe bleeding was also reduced from 0.8% in the heparin group to 0.2% in the bivalirudin group. Both differences were statistically significant.

They further analysed the rate of stent thrombosis, finding that this was also lower in the bivalirudin group at 0.4% compared with 1.1% in the heparin group.

“These results are dramatic,” Stone said. “The simple decision to use bivalirudin during primary PCI in patients with heart attacks, which is now generic and thus inexpensive, can save hundreds of thousands of lives per year and prevent major bleeding and stent thrombosis compared with heparin.” ensure frequent follow-ups, prescription reminders, and counselling to target challenges to medical adherence.”

The BRIGHT-4 trial was an investigator sponsored and organised trial, funded by the Chinese Society of Cardiology Foundation with a research grant from Jiangsu Hengrui Pharmaceuticals.

Those with depression had similarly decreased likelihood of optimal 12-month adherence to antiplatelets, β-blockers, and statins as well as renin-angiotensin-aldosterone system inhibitors (OR, 0.87; 95% CI, 0.82–0.94), the researchers report.

“These results indicate the critical importance of strategies to address depression as part of secondary cardiovascular disease prevention,” Lapa et al write. “The American Heart Association has advised depression screening for all patients with coronary disease given the adverse contribution of depression to cardiac prognosis. However, depression commonly goes unrecognised and undertreated in clinical settings.

The study’s authors note that their research has several limitations, chiefly that it only included individuals with insurance, the potential for misclassification of depression status due to reliance on claims data, the use of records from prescription fills to determine adherence, and finally the potential for residual confounding from unmeasured variables that may be associated with depression and adherence.

Patients with depression 10–20% less likely to adhere to guideline-directed medical therapy after PCI

“Either due to resistance from patients to report their depressive symptoms or poor screening practices, our findings of depression negatively affecting medication adherence could be underestimated. We advocate for multidisciplinary interventions to

“This cohort study of healthcare claims found an association between depression and likelihood of adequate or optimal 12-month adherence to essential guideline-directed medical therapy agents following PCI,” the study concludes. “Further studies are needed to determine whether treatment of depression may improve medication adherence as well as how such treatment improves secondary prevention of cardiovascular disease.”

Otsuka Medical Devices and ReCor Medical submit premarket approval of Paradise ultrasound renal denervation system

Otsuka Medical Devices and ReCor Medical have announced the filing of the premarket approval (PMA) application to the US Food and Drug Administration (FDA) for the Paradise ultrasound renal denervation system (uRDN) system in the treatment of uncontrolled hypertension.

The Paradise uRDN system is designed to reduce sympathetic nerve activity by denervating nerves which surround the renal arteries with the goal of reducing blood pressure, and uses a combination of ultrasound energy to denervate the renal nerves and a waterfilled balloon to protect the renal artery. The system employs an interventional procedure in which a catheter is placed in each of the main renal arteries, following which two to three sevensecond ultrasound emissions are delivered to denervate the surrounding renal nerves, thereby reducing blood pressure.

Since 2009, ReCor has been focused on developing and testing the Paradise system to treat hypertension safely and effectively. ReCor has three global, independently powered, sham-controlled randomised clinical trials of the Paradise system in more than 500 patients with uncontrolled hypertension: RADIANCE-HTN SOLO, RADIANCE-HTN TRIO and RADIANCE II. Each RADIANCE trial met its prespecified primary efficacy endpoint of blood pressure reduction, with positive safety.

RADIANCE II is the US FDA’s investigational device exemption (IDE) pivotal trial. In September 2022, ReCor and Otsuka Medical Devices announced that the trial successfully reached its primary efficacy endpoint. Results showed a reduction in daytime systolic ambulatory blood pressure of -7.9 mmHg in those treated with uRDN and a difference between uRDN and sham of -6.3 mmHg (p <0.0001). The results from the all three RADIANCE clinical trials have been included in the submission for approval to the FDA.

The Paradise system bears the CE mark for the treatment of hypertension in Europe and is an investigational device in the USA and Japan.

First US procedure performed using ShortCut leaflet splitting device

Pi-Cardia has announced that the first patient in the USA has been successfully treated with ShortCut—a dedicated device designed to split the leaflets of a pre-existing valve to enable safe transcatheter aortic valve implantation (TAVI) in patients at risk for coronary obstruction.

Pi-Cardia received Investigational Device Exemption (IDE) approval from the US Food and Drug Administration (FDA) to commence the ShortCut Pivotal Study in July 2022 and multiple patients have already been treated successfully outside the USA.

The ShortCut procedure was performed at Morristown Medical Center (Morristown, USA), by Philippe Généreux, Jim Slater, Leo Marcoff, and Robert Kipperman, in collaboration with Benjamin Seguy (Hospital Haut Leveque, Bordeaux, France).

“We successfully treated this patient with a degenerated valve who was at risk of coronary obstruction after TAVI with the ShortCut device,” said Généreux. “The targeted leaflet was effectively split within just a few minutes, allowing for safe implantation of the TAVI valve. ShortCut is a real game-changer enabling TAVI treatment in younger patients who will likely need multiple interventions over the course of their lives.” indications; as well as occlusive disease of the superficial femoral artery (SFA); and coronary in-stent restenosis.

Enrolment of the SELUTION SLR coronary de novo study will begin in the USA within the next few months.

This will complement the experience that the company has already gained with the SELUTION DeNOVO trial in Europe.

More than 800 patients of the 3,326 planned have been enrolled in this coronary randomised controlled study comparing Selution SLR versus any limus drug-eluting stent (DES). The study is powered to demonstrate superiority of Selution SLR drugeluting balloon (DEB) over DES in coronary de novo artery disease.

“Treatment of de novo coronary arteries with drug-eluting balloons is a breakthrough in revascularisation of coronary artery disease. The SELUTION SLR coronary de novo study is the first of its kind in the USA and will provide important data on the efficacy and safety of sirolimuseluting balloon as a viable alternative to drug-eluting stent, leaving nothing behind post-percutaneous coronary intervention (PCI) and eliminating in-stent restenosis and related complications,” said Ron Waksman (MedStar Heart and Vascular Institute, Washington DC, USA), chairman of the MedAlliance Coronary Study Steering Committee.

Selution SLR was awarded CE mark approval for the treatment of peripheral artery disease in February 2020 and for the treatment of coronary artery disease in May 2020.

US FDA approves use of Navitor TAVI valve in highrisk aortic stenosis patients

The US Food and Drug Administration (FDA) has approved the Navitor (Abbott) transcatheter aortic valve implantation (TAVI) system for the treatment of severe aortic stenosis among patients who are at high or extreme risk for open-heart surgery.

system, which features a slim design to accommodate different patient anatomies and small vessels for stable, predictable and accurate valve delivery and placement.

Michael Dale, senior vice president of Abbott’s structural heart business, said: “Navitor is the first TAVI system to offer optimal haemodynamics in all valve sizes while also preserving options for lifetime disease management, an important consideration for physicians and patients when selecting a TAVI solution.”

MedAlliance’s Selution SLR receives coronary de novo IDE approval

Selution SLR, MedAlliance’s novel sirolimus-eluting balloon, has received conditional US Food and Drug Administration (FDA) investigational device exemption (IDE) approval to initiate its pivotal clinical trial for the treatment of coronary de novo lesions.

This comes less than eight months after the company received its first IDE approval for Selution SLR in the treatment of below-the-knee (BTK)

“Abbott’s Navitor device features advancements to help doctors safely and effectively treat patients with aortic stenosis, including a design that reduces the backflow of blood around the valve that is often a complication following TAVI procedures,” said Michael Reardon (Houston Methodist Hospital, Houston, USA) who served as principal investigator for the study that led to FDA approval. “The innovative Navitor system also offers physicians stable and accurate device placement, even in challenging patient anatomies.”

Navitor features a fabric cuff— NaviSeal—to reduce or eliminate paravalvular leak (PVL), and Abbott describes the device as the only selfexpanding TAVI system with leaflets within the native valve; a feature intended to improve access to coronary arteries to facilitate future procedures for treating coronary artery disease.

The Navitor device is implanted using Abbott’s FlexNav delivery

CroíValve reports successful first-in-human implants of Duo tricuspid coaptation valve system

CroíValve has announced the successful first-in-human implants of its Duo tricuspid coaptation valve technology for the treatment of tricuspid regurgitation as part of its TANDEM I study in Poland.

The procedures were performed at the National Institute of Cardiology (Warsaw, Poland) by Adam Witkowski and Maciej Dąbrowski and the Medical University of Silesia (Katowice, Poland) by Wojciech Wojakowski.

The Duo system consists of a coaptation valve implant that works in tandem with the native tricuspid valve to restore valve function. The device is secured using a novel anchor system which leaves the frail right heart chamber and native valve apparatus untouched. The implant procedure uses standard imaging and is suitable for a broad patient cohort, including those who are challenging to treat with other valve repair and replacement technologies, the company said in a press release.

“The Duo system is unique in providing a solution that can effectively treat the dilated right heart anatomy that accompanies tricuspid regurgitation, while avoiding contact with the right heart to maintain normal cardiac motion,” commented Witkowski. “After 30 days, our patient has already experienced a transformative improvement in symptoms, highlighted by the Kansas City Cardiomyopathy Questionnaire (KCCQ) Quality of Life survey and a reduction from New York Heart Association (NYHA) III to NYHA II and significant improvement in six-minute walk test. In addition, the device continues to exhibit excellent efficacy.”