Background Current guidelines for patients with moderate-or high-risk acute coronary syndromes recommend an early invasive approach with concomitant antithrombotic therapy, including aspirin, clopidogrel, unfractionated or low-molecular-weight heparin, and glycoprotein IIb/IIIa inhibitors. We evaluated the role of thrombin-specific anticoagulation with bivalirudin in such patients. Methods We assigned 13,819 patients with acute coronary syndromes to one of three antithrombotic regimens: unfractionated heparin or enoxaparin plus a glycoprotein IIb/IIIa inhibitor, bivalirudin plus a glycoprotein IIb/IIIa inhibitor, or bivalirudin alone. The primary end points were a composite ischemia end point (death, myocardial infarction, or unplanned revascularization for ischemia), major bleeding, and the net clinical outcome, defined as the combination of composite ischemia or major bleeding. Results Bivalirudin plus a glycoprotein IIb/IIIa inhibitor, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with noninferior 30-day rates of the composite ischemia end point (7.7% and 7.3%, respectively), major bleeding (5.3% and 5.7%), and the net clinical outcome end point (11.8% and 11.7%). Bivalirudin alone, as compared with heparin plus a glycoprotein IIb/IIIa inhibitor, was associated with a noninferior rate of the composite ischemia end point (7.8% and 7.3%, respectively; P = 0.32; relative risk, 1.08; 95% confidence interval [CI], 0.93 to 1.24) and significantly reduced rates of major bleeding (3.0% vs. 5.7%; P<0.001; relative risk, 0.53; 95% CI, 0.43 to 0.65) and the net clinical outcome end point (10.1% vs. 11.7%; P = 0.02; relative risk, 0.86; 95% CI, 0.77 to 0.97). Conclusions In patients with moderate-or high-risk acute coronary syndromes who were undergoing invasive treatment with glycoprotein IIb/IIIa inhibitors, bivalirudin was associated with rates of ischemia and bleeding that were similar to those with heparin. Bivalirudin alone was associated with similar rates of ischemia and significantly lower rates of bleeding. (ClinicalTrials.gov number, NCT00093158.

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Major bleeding is a powerful independent predictor of 30-day mortality in patients with ACS managed invasively. Several factors independently predict major bleeding, including treatment with heparin plus GPI compared with bivalirudin monotherapy. Knowledge of these findings might be useful to reduce bleeding risk and improve outcomes in ACS.

Patients with ACS have marked variation in their risk of major bleeding. A simple risk score based on 6 baseline measures plus anticoagulation regimen identifies patients at increased risk for non-CABG-related bleeding and subsequent 1-year mortality, for whom appropriate treatment strategies can be implemented.

Background There is no angiographically demonstrable obstructive coronary artery disease (CAD) in a significant minority of patients with myocardial infarction (MI), particularly women. We sought to determine mechanism(s) of MI in this setting using multiple imaging techniques. Methods and Results Women with MI were enrolled prospectively, prior to angiography if possible. Women with ≥50% angiographic stenosis or use of vasospastic agents were excluded. Intravascular ultrasound (IVUS) was performed during angiography and cardiac magnetic resonance imaging (CMR) within one week. Fifty women (age 57±13 years) had median peak troponin 1.60 ng/ml; 11 had ST elevation. Median diameter stenosis of the worst lesion was 20% by angiography; 15 patients (30%) had normal angiograms. Plaque disruption was observed in 16/42 patients (38%) undergoing IVUS. There were abnormal myocardial CMR findings in 26/44 patients (59%) undergoing CMR: late gadolinium enhancement (LGE) in 17 and T2 signal hyperintensity indicating edema in 9 additional patients. The most common LGE pattern was ischemic (transmural/subendocardial). Non-ischemic LGE patterns (midmyocardial/subepicardial) were also observed. LGE was infrequent with plaque disruption but T2 signal hyperintensity was common with plaque disruption. Conclusions Plaque rupture and ulceration are common in women with MI without angiographically demonstrable obstructive CAD. LGE is also common in this cohort of women, with an ischemic pattern of injury most evident. Vasospasm and embolism are possible mechanisms of ischemic LGE without plaque disruption. IVUS and CMR provide complementary mechanistic insights in female MI patients without obstructive CAD and may be useful in identifying potential etiologies and therapies.