Post-PCI bivalirudin infusion reduces death, bleeding vs heparin

Patients with ST-elevation myocardial infarction (STEMI) who undergo primary percutaneous coronary intervention (PCI) have a reduced risk of all-cause death or BARC* type 3–5 bleeding when they receive a bolus plus post-PCI high-dose infusion of bivalirudin compared with heparin monotherapy, results of the BRIGHT**-4 trial showed.

The multicentre (87 sites in China), open-label trial included 6,016 patients (median age 61 years, 21.5 percent female) with STEMI undergoing primary PCI with radial access within 48 hours of symptom onset. They were randomized 1:1 to receive bivalirudin (0.75 mg/kg bolus followed by 1.75 mg/kg/hour infusion for 2–4 hours post-PCI [median 3 hours]) or unfractionated heparin monotherapy (70 IU/kg bolus) during primary PCI.

The use of provisional glycoprotein IIb/IIIa inhibitors (GPIs) for procedural thrombolytic complications was allowed, with use documented in 11.5 and 13.7 percent in the bivalirudin and heparin groups, respectively (p=0.01). Radial artery access was used in 93.1 percent.

Patients on thrombolytic therapy, with a history of anticoagulant or GPI use, or with mechanical complications of MI were excluded. The use of additional bolus, administered if activated clotting time (ACT) was <225 seconds, was greater in the heparin than bivalirudin group (35.1 percent vs 3.5 percent; p<0.0001). Peak ACT was lower in the heparin vs bivalirudin group (median 267 vs 321 seconds; p<0.0001).

At 30 days, the composite of all-cause death or BARC type 3–5 bleeding was significantly reduced among patients assigned to bivalirudin compared with heparin (3.1 percent vs 4.4 percent; hazard ratio [HR], 0.69, 95 percent confidence interval [CI], 0.53–0.91; p=0.0070), with 76 patients needing to be treated to prevent one event. [AHA 2022, session LBS.06]

The reduced risk was consistent for both components of the composite outcome (all cause death: 3.0 percent vs 3.9 percent; HR, 0.75, 95 percent CI, 0.57–0.99; p=0.0420; BARC type 3–5 bleeding: 0.2 percent vs 0.8 percent; HR, 0.21, 95 percent CI, 0.08–0.54; p=0.0014).

The reduced risk of BARC type 3–5 bleeding was primarily due to differences in non-access site-related bleeding between the bivalirudin and heparin groups (0.2 percent vs 0.8 percent; HR, 0.22; p=0.0019), with no significant between-group difference for access site bleeding (0 vs 0.03 percent).

The risk of reinfarction at 30 days was not significantly different between patients in the bivalirudin and heparin groups (0.6 percent vs 0.8 percent; HR, 0.68; p=0.22), nor was stroke (0.5 percent each; HR, 1.07; p=0.85) or ischaemia-driven target vessel revascularization (0.3 percent vs 0.6 percent; HR, 0.50; p=0.09). However, the risk of stent thrombosis was significantly reduced among patients assigned to bivalirudin vs heparin (0.4 percent vs 1.1 percent; HR, 0.33; p=0.0015), both at <24 hours post-procedure (0.1 percent vs 0.5 percent; HR, 0.29; p=0.0268) and at 1–30 days (0.2 percent vs 0.6 percent; HR, 0.37; p=0.0231).

The risk of major adverse cardiac and cerebral events was comparable between the bivalirudin and heparin groups (4.1 percent vs 5.2 percent; HR, 0.79; p=0.0509), while the risk of net adverse clinical events (NACE) was reduced with bivalirudin (4.2 percent vs 5.6 percent; HR, 0.74; p=0.0124).

Prior studies comparing these two therapies in this setting have produced conflicting results, said study author Professor Gregg Stone from the Mount Sinai Health System, New York, US, who presented the results at AHA 2022.

“[This was] in part due to whether a GPI was routinely used with heparin, whether a post-PCI infusion was used after bivalirudin, and whether intervention was via femoral or radial vascular access,” he continued.

“[In BRIGHT-4,] among patients with STEMI undergoing primary PCI with radial artery access, bivalirudin with a median 3-hour post-PCI high-dose infusion reduced the 30-day composite of all-cause mortality or BARC types 3–5 major bleeding compared with heparin monotherapy,” said Stone.

According to discussant Professor Philippe Gabriel Steg from the Hôpital Bichat, Assistance Publique–Hôpitauxde Paris, Paris, France, results of the BRIGHT-4 trial present a clear win for bivalirudin at 30 days. However, bivalirudin remains slightly more complex and more expensive than unfractionated heparin. As such, longer term follow-up and cost-effectiveness studies are warranted before these outcomes lead to changes in practice.