BRIGHT-4 Study Compares Bivalirudin and Heparin for STEMI Patients Undergoing PCI

November 6, 2022—Mount Sinai Heart announced findings from the BRIGHT-4 study showing that bivalirudin is a safer and more effective anticoagulant than heparin for treating patients with the most serious type of heart attacks who undergo urgent percutaneous coronary intervention (PCI) and can lower the risk of death or major bleeding by 31%. These findings are from a new study led by investigators from the Icahn School of Medicine at Mount Sinai, part of the Mount Sinai Health System in New York, New York.

According to Mount Sinai, this is the first large-scale clinical trial to compare the two anticoagulants most widely used after PCI. It shows bivalirudin given with a 2- to 4-hour high-dose infusion significantly reduces death, major bleeding, and thrombosis when compared with heparin. Additionally, Mount Sinai stated, this investigation could have broad implications, changing the treatment course for ST-segment elevation myocardial infarction (STEMI).

BRIGHT-4 was an investigator-sponsored/organized trial funded by the Chinese Society of Cardiology Foundation with a research grant from Jiangsu Hengrui Pharmaceuticals Co., Ltd.

The results were announced in a Late Breaking Clinical Trial presentation at the American Heart Association Scientific Sessions 2022 held November 5-7 in Chicago, Illinois. Simultaneously, the study was published by Yi Li, MD, et al online in The Lancet.

Gregg W. Stone, MD, is the study’s Coprincipal Investigator. Dr. Stone is Director of Academic Affairs for the Mount Sinai Health System and Professor of Medicine (Cardiology) and Population Health Science and Policy at Icahn Mount Sinai.

“For the first time, this study identifies the best and safest treatment course for patients undergoing stenting to treat a STEMI heart attack,” commented Dr. Stone in the Mount Sinai press release. “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 patients to receive anticoagulant therapy. Heparin and bivalirudin have been compared in six previous large, randomized trials in patients with STEMI, but in those studies, they were administered with varying regimens and background therapies. The BRIGHT-4 study evaluated the two most widely used regimens of heparin and bivalirudin, which have never been directly compared with each other in an adequately sized trial, noted the Mount Sinai press release.

Dr. Stone and Yaling Han, MD, of Shenyang Northern Hospital in Shenyang, China, led a team of investigators who analyzed 6,106 patients enrolled in the study across 87 sites in China between February 2019 and April 2022.

As summarized in the Mount Sinai press release, all patients in the study underwent primary PCI for STEMI treatment, nearly all via radial access (93.1%). The patients were randomized to receive the two most widely used regimens of heparin and bivalirudin, which previous studies have shown to be the safest and most effective. One group (n = 3,007) received heparin alone, administered intravenously. The other group (n = 3,009) received bivalirudin intravenously, followed by a high-dose intravenous infusion for 2 to 4 hours after the procedure.

Investigators followed patients for 30 days after the procedure, the timeframe in which STEMI patients are at highest risk for adverse events, noted Mount Sinai.

The primary goal of the study was to compare the occurrence of all-cause mortality or major bleeding. The investigators 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 investigators 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 3.0% in bivalirudin-treated patients (hazard ratio [HR], 0.75; 95% CI, 0.57-0.99; P = .0420). Severe bleeding also was reduced from 0.8% in the heparin group to 0.2% in the bivalirudin group (HR, 0.21; 95% CI, 0.08-0.54; P = .0014). Both differences were statistically significant.

Finally, the investigators also analyzed the rate of stent thrombosis, which was lower in the bivalirudin group at 0.4% compared with 1.1% in the heparin group (P = .0015), a statistically significant reduction.

“These results are dramatic,” concluded Dr. Stone in the Mount Sinai press release. “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.”