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 findings from a new study led by researchers from the Icahn School of Medicine at Mount Sinai (New York, USA). This is the first large-scale 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 (AHA) 2022 Scientific Sessions (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,” says 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, 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 the procedure. 

Investigators followed patients for 30 days following the procedure. The primary goal of the study was to compare the occurrence of all-cause 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 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. 

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 bivalirudin-treated patients. Severe bleeding also was reduced from 0.8% in the heparin group to 0.2% in the bivalirudin group. Both differences were statistically significant. 

They also 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.” 

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.


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