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Aims Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS. Methods and results In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding Occurring>30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 [relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P<0.001] and BARC 3a bleeding (RR 2.23; 95% CI 1.36-3.64; P =0.001), and a risk similar to BARC 3b bleeding (RR 1.37; 95% CI 0.81-2.30; P=0.242). Risk of death after MI was significantly lower than after BARC 3c bleeding (RR 0.22; 95% CI 0.13-0.36; P<0.001). MI and bleeding had similar time-associations with mortality, which remained significant for several months, still being higher early after the event. Conclusion In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.

Objective: To investigate whether the beneficial and harmful effects of platelet glycoprotein IIb/IIIa receptor blockers in non-ST elevation acute coronary syndromes (NSTE-ACS) depend on age. Methods: A meta-analysis of six trials of platelet glycoprotein IIb/IIIa receptor blockers in patients with NSTE-ACS (PRISM, PRISM-PLUS, PARAGON-A, PURSUIT, PARAGON-B, GUSTO IV-ACS; n = 31 402) was performed. We applied multivariable logistic regression analyses to evaluate the drug effects on death or non-fatal myocardial infarction at 30 days, and on major bleeding, by age subgroups (<60, 60–69, 70–79, >=80 years). We quantified the reduction of death or myocardial infarction as the number needed to treat (NNT), and the increase of major bleeding as the number needed to harm (NNH). Results: Subgroups had 11 155 (35%), 9727 (31%), 8468 (27%) and 2049 (7%) patients, respectively. The relative benefit of platelet glycoprotein IIb/IIIa receptor blockers did not differ significantly (p = 0.5) between age subgroups (OR (95% CI) for death or myocardial infarction: 0.86 (0.74 to 0.99), 0.90 (0.80 to 1.02), 0.97 (0.86 to 1.10), 0.90 (0.73 to 1.16); overall 0.91 (0.86 to 0.99). ORs for major bleeding were 1.9 (1.3 to 2.8), 1.9 (1.4 to 2.7), 1.6 (1.2 to 2.1) and 2.5 (1.5–4.1). Overall NNT was 105, and overall NNH was 90. The oldest patients had larger absolute increases in major bleeding, but also had the largest absolute reductions of death or myocardial infarction. Patients >=80 years had half of the NNT and a third of the NNH of patients <60 years. Conclusions: In patients with NSTE-ACS, the relative reduction of death or non-fatal myocardial infarction with platelet glycoprotein IIb/IIIa receptor blockers was independent of patient age. Larger absolute outcome reductions were seen in older patients, but with a higher risk of major bleeding. Close monitoring of these patients is warranted.

AIM: To study the relationship between outcomes and peak creatine kinase (CK)-MB levels after percutaneous coronary intervention (PCI) in patients with non-ST-segment elevation acute coronary

BACKGROUND: The prognosis of ventricular arrhythmias among patients with non-ST-elevation acute coronary syndromes is unknown. We studied the incidence, predictors, and outcomes of sustained ventricular arrhythmias in 4 large randomized trials of such patients. METHODS AND RESULTS: We pooled the datasets of the Global Use of Streptokinase and tPA for Occluded Arteries (GUSTO)-IIb, Platelet Glycoprotein IIb/IIIa in Unstable Angina: Receptor Suppression Using Integrilin Therapy (PURSUIT), Platelet IIb/IIIa Antagonism for the Reduction of Acute Coronary Syndrome Events in a Global Organization Network (PARAGON)-A, and PARAGON-B trials (n=26 416). We identified independent predictors of ventricular fibrillation (VF) and ventricular tachycardia (VT) and compared the 30-day and 6-month mortality rates of patients who did (n=552) and did not (n=25 864) develop these arrhythmias during the index hospitalization. Independent predictors of in-hospital VF included prior hypertension, chronic obstructive pulmonary disease, prior myocardial infarction, and ST-segment changes at presentation. Except for hypertension, these variables also independently predicted in-hospital VT. In Cox proportional-hazards modeling, in-hospital VF and VT were independently associated with 30-day mortality (hazard ratio [HR], 23.2 [95% CI, 18.1 to 29.8] for VF and HR, 7.6 [95% CI, 5.5 to 10.4] for VT) and 6-month mortality (HR, 14.8 [95% CI, 12.1 to 18.3] for VF and HR, 5.0 [95% CI, 3.8 to 6.5] for VT). These differences remained significant after excluding patients with heart failure or cardiogenic shock and those who died <24 hours after enrollment. CONCLUSIONS: Despite the use of effective therapies for non-ST-elevation acute coronary syndromes, ventricular arrhythmias in this setting are associated with increased 30-day and 6-month mortality. More effective therapies are needed to improve the survival of patients with these arrhythmias.