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Background There are limited data on how the combination of diabetes mellitus ( DM ) and chronic kidney disease ( CKD ) affects cardiovascular outcomes as well as response to different P2Y 12 receptor antagonists, which represented the aim of the present investigation. Methods and Results In this post hoc analysis of the PLATO (Platelet Inhibition and Patient Outcomes) trial, which randomized acute coronary syndrome patients to ticagrelor versus clopidogrel, patients (n=15 108) with available DM and CKD status were classified into 4 groups: DM +/ CKD + (n=1058), DM +/ CKD - (n=2748), DM -/ CKD + (n=2160), and DM -/ CKD - (n=9142). The primary efficacy end point was a composite of cardiovascular death, myocardial infarction, or stroke at 12 months. The primary safety end point was PLATO major bleeding. DM +/ CKD + patients had a higher incidence of the primary end point compared with DM -/ CKD - patients (23.3% versus 7.1%; adjusted hazard ratio 2.22; 95% CI 1.88-2.63; P<0.001). Patients with DM +/ CKD - and DM -/ CKD + had an intermediate risk profile. The same trend was shown for the individual components of the primary end point and for major bleeding. Compared with clopidogrel, ticagrelor reduced the incidence of the primary end point consistently across subgroups ( P-interaction=0.264), but with an increased absolute risk reduction in DM +/ CKD +. The effects on major bleeding were also consistent across subgroups ( P-interaction=0.288). Conclusions In acute coronary syndrome patients, a gradient of risk was observed according to the presence or absence of DM and CKD , with patients having both risk factors at the highest risk. Although the ischemic benefit of ticagrelor over clopidogrel was consistent in all subgroups, the absolute risk reduction was greatest in patients with both DM and CKD . Clinical Trial Registration URL : http://www.clinicatrials.gov . Unique identifier: NCT 00391872.

Objective: We aimed to study the relationships between left anterior hemiblock (LAHB) and the patient characteristics, management, and clinical outcomes in the setting of acute coronary syndromes (ACS)., Methods: Admission ECGs of patients enrolled in the Global Registry of Acute Coronary Events (GRACE) ECG substudy, and the Canadian ACS Registry I, were analysed independently at a blinded core laboratory. Multivariable logistic regression analysis was performed to assess the independent associations between LAHB on the admission ECG and in-hospital and 6-month mortality., Results: Of the 11 820 eligible ACS patients, 692 (5.9%) patients had LAHB. The presence of LAHB on admission was associated with older age, male sex, prior myocardial infarction, prior heart failure, worse Killip class, higher creatinine level, and higher GRACE risk score (all p<0.01). Patients with LAHB less frequently underwent cardiac catheterisation, coronary revascularisation or reperfusion therapy (all p<0.05). The LAHB group had higher in-hospital (6.9% vs 3.9%, p<0.001) and 6-month mortality (12.5% vs 7.7%, p<0.001). However, after adjusting for the known predictors of mortality in the GRACE risk models, LAHB was not independently associated with in-hospital death (OR 1.07, 95% CI 0.76 to 1.52, p=0.70), or death at 6 months (OR 1.00, 95% CI 0.75 to 1.34, p=0.99)., Conclusions: Across the broad spectrum of ACS, LAHB was associated with significant comorbidities, high-risk clinical features on presentation, and worse unadjusted outcomes. However, LAHB was not an independent predictor of in-hospital and 6-month mortality and did not carry incremental prognostic value beyond the known prognosticators in the GRACE risk models., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)