STEACS and the Use of Bivalirudin vs. Heparin: In Search of BRIGHT-4 Outcomes

Various studies and registries have previously shown the impact of post-percutaneous coronary intervention (PCI) complications on the survival of patients with ST-segment elevation acute coronary syndrome (STEACS). Complications such as major bleeding or ischemic events (like recurrent acute myocardial infarction or stent thrombosis) negatively affect prognosis. Therefore, selecting an appropriate antithrombotic treatment that minimizes these risks is crucial. The two most studied anticoagulants for this purpose are heparin and bivalirudin.

In the BRIGHT-4 study, 6016 patients undergoing primary PCI were randomized to receive bivalirudin with a post-PCI 2-4-hour infusion or heparin. There was a reduction in all-cause mortality at 30 days (hazard ratio [HR]: 0.75; 95% confidence interval [CI]: 0.57-0.99) and in the risk of major bleeding (HR: 0.21; 95% CI: 0.08-0.54), without an increase in thrombotic events. Despite these results, the 2023 European guidelines continue to recommend heparin as the preferred anticoagulant, suggesting bivalirudin as an alternative.

The aforementioned recommendation is largely due to the fact that the BRIGHT-4 study was open-label and included only Chinese patients. To validate these results, researchers conducted an analysis of the most relevant randomized studies on bivalirudin and heparin, creating an individual patient data (IPD) “pool” to assess the outcomes for BRIGHT-4.

The pre-specified primary endpoint was all-cause mortality at 30 days. Secondary endpoints included cardiac mortality, myocardial infarction (MI), stent thrombosis, stroke, and major adverse cardiovascular events (MACE). The analysis included six randomized studies with ≥1000 STEACS patients undergoing primary PCI: EUROMAX, HEAT-PPCI, HORIZONS-AMI, the first BRIGHT, MATRIX, and VALIDATE-SWEDEHEART. This resulted in a population of 15,254 patients for the IPD.

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The average duration of the post-PCI infusion was 169 minutes in 65.5% of cases, classified as high dose (72.4%) and low dose (21.3%). Among patients randomized to heparin, 43.6% received IIb-IIIa inhibitors (GPI) before PCI.

Unplanned use of IIb-IIIa inhibitors post-PCI due to complications was lower in the bivalirudin group compared with the heparin group without planned GPI use (8.6% vs. 10.1%; P <0.001). At 30 days, mortality was lower among patients treated with bivalirudin (adjusted odds ratio [OR]: 0.78; 95% CI: 0.62-0.99; P = 0.04), and so was cardiac mortality (2.1% vs. 2.7%; adjusted OR: 0.69; 95% CI: 0.54-0.88; P = 0.003). Rates of reinfarction and stent thrombosis were also evaluated.

When comparing heparin plus planned GPI use with post-PCI bivalirudin infusion, there was a lower all-cause mortality rate, with similar rates of stent thrombosis and reinfarction. However, the absence of post-PCI infusion was associated with increased mortality, reinfarction, and stent thrombosis. These findings were similar to those observed with low-dose infusion.

When comparing with a protocol similar to BRIGHT-4, where high-dose post-PCI bivalirudin infusion was used vs. heparin without IIb-IIIa inhibitors, there was a lower need for rescue GPI inhibitors (3.3% vs. 8.2%; P <0.0001) and a reduction in all-cause mortality (HR: 0.75; 95% CI: 0.57-0.99).

Conclusions

In this analysis of studies preceding BRIGHT-4, where attempts were made to target similar populations, it was found that the use of a high-dose bivalirudin infusion was associated with a reduction in all-cause mortality and cardiac mortality. The absence of post-PCI infusion was linked to a higher risk of ischemic events, such as stent thrombosis.

Original Title: Bivalirudin vs Heparin Anticoagulation in STEMI Confirmation of the BRIGHT-4 Results.

Reference: Stone GW, Valgimigli M, Erlinge D, Han Y, Steg PG, Stables RH, Frigoli E, James SK, Li Y, Goldstein P, Mehran R, Mehdipoor G, Crowley A, Chen S, Redfors B, Snyder C, Zhou Z, Bikdeli B. Bivalirudin vs Heparin Anticoagulation in STEMI: Confirmation of the BRIGHT-4 Results. J Am Coll Cardiol. 2024 Oct 15;84(16):1512-1524. doi: 10.1016/j.jacc.2024.07.045. PMID: 39384262.