Impact of diabetes mellitus on the safety and effectiveness of bivalirudin in patients with acute myocardial infarction undergoing primary angioplasty: analysis from the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocard

We sought to evaluate the safety and efficacy of bivalirudin compared with glycoprotein IIb/IIIa inhibitors (GPI) in diabetic patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI). Prior studies have demonstrated that GPI are especially beneficial in patients with diabetes with acute coronary syndromes and/or those undergoing PCI. In the multicenter, prospective HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients with STEMI were randomized to bivalirudin or unfractionated heparin plus a GPI. Clinical outcomes were analyzed at 30 days and 1 year in patients with diabetes. Diabetes mellitus was present in 593 patients (16.5%). The rates of cardiac death were significantly lower in diabetic patients treated with bivalirudin compared with heparin plus GPI (30 days: 2.1% vs. 5.5%, p = 0.04; 1 year: 2.5% vs. 7.1%, p = 0.01), and bivalirudin resulted in lower 30-day rates of stroke (0% vs. 2%, p = 0.02). There were no significant differences among diabetic patients randomized to bivalirudin versus heparin plus GPI in the 1-year rates of major adverse cardiac events (14.2% vs. 16.2%, p = 0.44), major bleeding (8.7% vs. 10.7%, p = 0.42), or stent thrombosis (4.2% vs. 3.8%, p = 0.85). By interaction testing, the relative effects of bivalirudin compared with heparin plus GPI were not significantly different in patients with and without diabetes. In patients with diabetes mellitus presenting with STEMI undergoing primary PCI, anticoagulant therapy with bivalirudin compared with heparin plus GPI is safe and effective and might reduce cardiac mortality at 30 days and 1 year. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Witzenbichler B ，Mehran R ，Guagliumi G ，Dudek D ，Huber K ，Kornowski R ，Stuckey TD ，Fahy M ，Parise H ，Stone GW ... -  《-》

Reduction in cardiac mortality with bivalirudin in patients with and without major bleeding: The HORIZONS-AMI trial (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction).

The purpose of this study was to determine whether, in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI), the reduction in cardiac mortality in those taking bivalirudin compared with unfractionated heparin plus a glycoprotein IIb/IIIa inhibitor (UFH+GPI) can be fully attributed to reduced bleeding. The association between hemorrhagic complications and mortality may explain the survival benefit with bivalirudin. A total of 3,602 STEMI patients undergoing primary PCI were randomized to bivalirudin versus UFH+GPI. Three-year cardiac mortality was analyzed in patients with and without major bleeding. When compared with UFH+GPI, bivalirudin resulted in lower 3-year rates of major bleeding (6.9% vs. 10.5%, hazard ratio [HR]: 0.64 [95% confidence interval (CI): 0.51 to 0.80], p < 0.0001) and cardiac mortality (2.9% vs. 5.1%, HR: 0.56 [95% CI: 0.40 to 0.80], p = 0.001). Three-year cardiac mortality was reduced in bivalirudin-treated patients with major bleeding (20 fewer deaths with bivalirudin; 5.8% vs. 14.6%, p = 0.025) and without major bleeding (18 fewer deaths with bivalirudin; 2.6% vs. 3.8%, p = 0.048). In a fully-adjusted multivariable model accounting for major bleeding and other adverse events, bivalirudin was still associated with a 43% reduction in 3-year cardiac mortality (adjusted HR: 0.57 [95% CI: 0.39 to 0.83], p = 0.003). Bivalirudin reduces cardiac mortality in patients with STEMI undergoing primary PCI, an effect that can only partly be attributed to prevention of bleeding. Further studies are required to identify the nonhematologic benefits of bivalirudin. (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction; NCT00433966).

Stone GW ，Clayton T ，Deliargyris EN ，Prats J ，Mehran R ，Pocock SJ ... -  《-》

Bivalirudin versus heparin with or without glycoprotein IIb/IIIa inhibitors in patients with STEMI undergoing primary percutaneous coronary intervention: pooled patient-level analysis from the HORIZONS-AMI and EUROMAX trials.

In the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial, 3,602 patients undergoing primary percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) treated with bivalirudin had lower bleeding and mortality rates, but higher acute stent thrombosis rates compared with heparin + a glycoprotein IIb/IIIa inhibitor (GPI). Subsequent changes in primary PCI, including the use of potent P2Y12 inhibitors, frequent radial intervention, and pre-hospital medication administration, were incorporated into the EUROMAX (European Ambulance Acute Coronary Syndrome Angiography) trial, which assigned 2,218 patients to bivalirudin versus heparin ± GPI before primary PCI. The goal of this study was to examine the outcomes of procedural anticoagulation with bivalirudin versus heparin ± GPI for primary PCI, given the evolution in primary PCI. Databases from HORIZONS-AMI and EUROMAX were pooled for patient-level analysis. The Breslow-Day test evaluated heterogeneity between trials. A total of 5,800 patients were randomized to bivalirudin (n = 2,889) or heparin ± GPI (n = 2,911). The radial approach was used in 21.3% of patients, prasugrel/ticagrelor was used in 18.1% of patients, and GPI was used in 84.8% of the control group. Bivalirudin compared with heparin ± GPI resulted in reduced 30-day rates of major bleeding (4.2% vs. 7.8%; relative risk [RR]: 0.53; 95% confidence interval [CI]: 0.43 to 0.66; p < 0.0001), thrombocytopenia (1.4% vs. 2.9%, RR: 0.48; 95% CI: 0.33 to 0.71; p = 0.0002), and cardiac mortality (2.0% vs. 2.9%; RR: 0.70; 95% CI: 0.50 to 0.97; p = 0.03), with nonsignificantly different rates of reinfarction, ischemia-driven revascularization, stroke, and all-cause mortality. Bivalirudin resulted in increased acute (<24 h) stent thrombosis rates (1.2% vs. 0.2%; RR: 6.04; 95% CI: 2.55 to 14.31; p < 0.0001), with nonsignificantly different rates of subacute stent thrombosis. Composite net adverse clinical events were lower with bivalirudin (8.8% vs. 11.9%; RR: 0.74; 95% CI: 0.63 to 0.86; p < 0.0001). There was no significant heterogeneity between the 2 trials for these outcomes, and results were consistent across major subgroups. Despite increased acute stent thrombosis, primary PCI with bivalirudin improved 30-day net clinical outcomes, with significant reductions in major bleeding, thrombocytopenia, and transfusions compared with heparin ± GPI, results that were consistent with evolution in PCI technique and pharmacotherapy. (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction [HORIZONS-AMI]; NCT00433966) (European Ambulance Acute Coronary Syndrome Angiography [EUROMAX]; NCT01087723).

Stone GW ，Mehran R ，Goldstein P ，Witzenbichler B ，Van't Hof A ，Guagliumi G ，Hamm CW ，Généreux P ，Clemmensen P ，Pocock SJ ，Gersh BJ ，Bernstein D ，Deliargyris EN ，Steg PG ... -  《-》

Long-term impact of chronic kidney disease in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention: the HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial In

This study sought to investigate the impact of chronic kidney disease (CKD) in patients undergoing percutaneous coronary intervention (PCI) for ST-segment elevation myocardial infarction (STEMI) with different antithrombotic strategies. CKD is associated with increased risk of adverse ischemic and hemorrhagic events after primary PCI for STEMI. HORIZONS-AMI (Harmonizing Outcomes With Revascularization and Stents in Acute Myocardial Infarction) trial was a multicenter, international, randomized trial comparing bivalirudin monotherapy or heparin plus a glycoprotein IIb/IIIa inhibitor (GPI) during primary PCI in STEMI. CKD, defined as creatinine clearance <60 ml/min, was present at baseline in 554 of 3,397 patients (16.3%). Patients were followed for 3 years. Net adverse cardiac event (NACE) was defined as the composite of death, reinfarction, ischemia-driven target vessel revascularization (TVR), stroke or non-coronary artery bypass grafting (CABG)-related major bleeding. Patients with CKD compared with patients without had higher rates of NACE (41.4% vs. 23.8%, p < 0.0001), death (18.7% vs. 4.4%, p < 0.0001), and major bleeding (19.3% vs. 6.7%, p < 0.0001). Multivariable analysis identified baseline creatinine as an independent predictor of death at 3 years (hazard ratio: 1.51, 95% confidence interval: 1.21 to 1.87, p < 0.001). Patients with CKD randomized to bivalirudin monotherapy versus heparin plus GPI had no significant difference in major bleeding (19.0% vs. 19.6%, p = 0.72) or death (19.0% vs. 18.4%, p = 0.88) at 3 years. In patients with CKD, there was no difference in the rates of TVR in bare-metal stents (BMS) versus drug-eluting stents (DES) at 3 years (14.1% vs. 15.1%, p = 0.8). STEMI patients with CKD have significantly higher rates of death and major bleeding compared with those without CKD. In patients with CKD, there appears to be no benefit of bivalirudin compared with heparin + GPI, or DES versus BMS during primary PCI in improving clinical outcomes.

Saltzman AJ ，Stone GW ，Claessen BE ，Narula A ，Leon-Reyes S ，Weisz G ，Brodie B ，Witzenbichler B ，Guagliumi G ，Kornowski R ，Dudek D ，Metzger DC ，Lansky AJ ，Nikolsky E ，Dangas GD ，Mehran R ... -  《-》

Impact of bivalirudin therapy in high-risk patients with acute myocardial infarction: 1-year results from the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial.

This study sought to assess the relationship between 1-year mortality and baseline patient risk in the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial. The HORIZONS-AMI trial showed that bivalirudin compared with unfractionated heparin (UFH) plus glycoprotein IIb/IIIa inhibitors (GPI) decreased major bleeding and 30-day and 1-year mortality in patients undergoing primary percutaneous intervention for acute myocardial infarction. Patients in the HORIZONS-AMI trial were classified as low, intermediate, and high risk according to the CADILLAC (Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications) risk score based on 7 clinical variables. Among 2,530 CADILLAC-score evaluable HORIZONS-AMI trial patients, 1,522 (60%) were classified as low risk, 531 (21%) as intermediate risk, and 477 (19%) as high risk. The mortality rates in the bivalirudin and UFH plus GPI arms, respectively, were 0.4% and 1.2% (p = 0.09) in the low-risk group, 4.2% and 4.1% (p = 0.99) in the intermediate-risk group, and 8.4% and 15.9% (p = 0.01) in the high-risk group. Among high-risk patients, there was also a decreased rate of recurrent myocardial infarction in patients randomized to bivalirudin as compared to UFH plus GPI (3.6% vs. 7.9%, p = 0.04). In high-risk patients undergoing primary percutaneous coronary intervention for acute myocardial infarction, bivalirudin compared with UFH plus GPI reduces 1-year mortality and recurrent myocardial infarction. (HORIZONS-AMI trial; NCT00433966).

Parodi G ，Antoniucci D ，Nikolsky E ，Witzenbichler B ，Guagliumi G ，Peruga JZ ，Stuckey T ，Dudek D ，Kornowski R ，Hartmann F ，Lansky AJ ，Mehran R ，Stone GW ... -  《-》