On April 7, 2015, the results of the BRIGHT study led by Academician Han Yaling were published in the journal JAMA. The results of this study showed that the application of bivalirudin in the perioperative period of acute percutaneous coronary intervention (PCI) for acute myocardial infarction (AMI) reduced the risk of bleeding and did not increase the risk of in-stent thrombosis compared with plain heparin or heparin combined with tirofiban, overcoming the increased risk of in-stent thrombosis in the HEAT-PPCI study. Academician Han reported the results of the BRIGHT study in CIT2014, TCT2014, which soon attracted the attention of cardiovascular experts from all over the world, and Medsacpe immediately published a news report with the title “Light From BRIGHT: More Fuel for Bivalirudin-Heparin Debate “The BRIGHT study was also named one of the “6 most important studies in the global cardiac interventional field” in 2014. As one of the 82 centers in China participating in the BRIGHT study, our center enrolled 30 patients with AMI for emergency PCI. This article will explain the BRIGHT study. Jia Shaobin, Department of Cardiovascular Medicine, General Hospital of Ningxia Medical University Background of the study: Whether the direct thrombin inhibitor bivalirudin can replace common heparin in the perioperative anticoagulation therapy of PCI is currently controversial. The results of the HORIZONS-AMI and EUROMAX studies published in recent years showed that compared with heparin + IIb/IIIa receptor antagonist (GPI), the perioperative application of bivalirudin during direct PCI in AMI significantly reduced the risk of bleeding and net adverse clinical events (NACE) and all-cause mortality, but increased the risk of acute in-stent thrombosis; while in the HEAT-PPCI study Bivalirudin did not reduce bleeding but increased ischemic events compared with heparin alone, with heparin outperforming bivalirudin. Therefore, it is unclear whether bivalirudin or heparin is better or worse. To investigate the efficacy and safety of domestic bivalirudin in the perioperative period of direct PCI in Chinese AMI patients, Academician Han conducted this clinically significant RCT. Study design: Between August 2012 and June 2013, 2,194 patients with a diagnosis of AMI undergoing emergency PCI were randomly enrolled in the BRIGHT study at 82 cardiac centers in mainland China with an annual direct PCI volume of >50 patients, using three different anticoagulation strategies: bivalirudin (preoperative pill injection combined with postoperative pumping), heparin alone, and heparin combined with tirofiban. The primary endpoint was 30-d net adverse clinical events (NACE), including all-cause death, reinfarction, ischemia-driven target revascularization, stroke, and bleeding, and the safety endpoints were: 30-d and 1-year in-stent thrombosis rates. Results: The 30-day postoperative NACE rate (including all-cause death, reinfarction, emergency target revascularization, stroke, and any bleeding) was significantly better in the bivalirudin group than in the other two groups (8.8%, 13.2%, and 17.0% in the bivalirudin, heparin, and heparin combined with tirofiban groups, respectively; P < 0.001). There was no significant difference in the incidence of serious adverse cardiovascular events at 30 d between the three groups (5.0%, 5.8%, and 4.9% in the bivalirudin, heparin, and heparin combined with tirofiban groups, respectively; P = 0.74). The overall reduction in bleeding events was 46% and 66% in the bivalirudin alone group compared with heparin alone and heparin combined with tirofiban, respectively, and there was no significant difference in the incidence of 30-day postoperative in-stent thrombosis (0.6%, 0.9%, 0.7%, P = 0.74, respectively) and acute in-stent thrombosis (0.3% in all) among the 3 groups, with similar results at 1-year follow-up. Bivalirudin was found to be of greater benefit by subgroup analysis in patients at high bleeding risk (female, renal insufficiency and high CRUSADE score). Interpretation of study results: The results of the BRIGHT study differed significantly from those of previous studies. For example, the HEAT-PPCI study randomized only patients with STEMI to direct PCI, whereas the BRIGHT study included both patients with STEMI (6.1 h from symptom onset to visit) and patients with Non-STEMI undergoing emergency PCI. There were significant differences in anticoagulation strategies between the studies, with anticoagulation administered before patients reached the catheterization laboratory in the HEAT-PPCI study and after patients entered the catheterization laboratory in the BRIGHT study. The optimal dose of heparin in the perioperative period of PCI is currently unknown, with current guidelines recommending a dose of 70 to 100 IU/kg. the dose of heparin used in the BRIGHT study was 100 U/kg, whereas in the EUROMAX and HEAT-PPCI studies the dose distribution of heparin was 60 U/kg and 70 U/kg. the incidence of major bleeding in the BRIGHT study was The incidence of major bleeding was 1.5% in the BRIGHT study and 6.3% and 3.1% in the EUROMAX and HEAT-PPCI studies. The incidence of in-stent thrombosis at 30 d in the BRIGHT study was 0.6%, which was not significantly different from the other two groups. In contrast, the incidence of in-stent thrombosis in the HORIZONS-AMI , EUROMAX and HEAT-PPCI studies was 1.3%, 1.1% and 2.9%, respectively, which was significantly higher than that in the heparin control group. A pooled analysis by HORIZONS-AMI and EUROMAX revealed that acute in-stent thrombosis occurred mainly within the first 4 h after patient enrollment, which may be related to the delayed onset of P2Y12 in the clinic and the empty window of antithrombotic therapy due to premature discontinuation of anticoagulation after PCI. the BRIGHT study, unlike the previous studies, used a strategy of continuous pumping after projectile injection, which prolonged the duration of bivalirudin administration. This antithrombotic strategy reduced the risk of in-stent thrombosis and bleeding. In a JAMA editorial, Dr. Faxon of Harvard Medical School noted that although, the BRIGHT study did not have prolonged bivalirudin to reduce ischemic events and in-stent thrombosis as its primary endpoint, it provides valuable evidence that prolonged bivalirudin injection after PCI is safe and can be an effective strategy to reduce in-stent thrombosis. At the same time, Dr. Rod Stables of Liverpool Cardiothoracic Hospital noted that extended bivalirudin injections are bound to increase the cost of treatment by about 1400 times the cost of regular heparin. However, Han pointed out that the BRIGHT study used bivalirudin, which is manufactured by Reliant, and is much more economical than Angiomax (bivalirudin). It is important to note that unlike the HORIZONS-AMI, the BRIGHT study failed to demonstrate a reduction in STEMI mortality with direct PCI, and the direct benefit was mainly in terms of a reduced risk of bleeding in patients. two meta-analyses published in 2014 that included the BRIGHT study showed that bivalirudin reduced the risk of bleeding but increased the risk of ischemic events. In light of this, the current European and US guidelines for the use of bivalirudin have been updated. the AHA 2013 STEMI guidelines and the 2014 NSTE-ACS treatment guidelines state that the recommendation level for perioperative bivalirudin for PCI is a Class I recommendation with Class B evidence. In contrast, in the 2014 European ESC Revascularization Guidelines, for Non-STEMI patients the recommendation level for bivalirudin is Class I recommendation, Class A evidence while for STEMI patients, the recommendation level for bivalirudin is lowered from Class IB to Class IIa, Class A evidence, and the recommendation level for plain heparin is upgraded to Class IC. In conclusion, whether bivalirudin can replace plain Heparin is still controversial. In the era of precision medicine, we need to individually assess the risk of bleeding and ischemic events in STEMI patients according to their condition, weigh the pros and cons, and develop individualized antithrombotic treatment regimens to reduce the risk of adverse cardiovascular events in patients. In the future, we need more RCTs like BRIGHT to provide strong evidence for the clinical application of bivalirudin.