Evaluation of the atrial fibrillation better care pathway in the ENGAGE AF-TIMI 48 trial.

AIMS: The Atrial fibrillation Better Care (ABC) pathway is endorsed by guidelines to improve care of patients with atrial fibrillation (AF). However, whether the benefit of ABC pathway-concordant care is consistent across anticoagulants remains unclear. We assessed the association between ABC-concordant care and outcomes in this post hoc analysis from the ENGAGE AF-TIMI 48 trial, which was reported prior to the initial description of the ABC pathway. METHODS AND RESULTS: Patients were retrospectively classified as receiving ABC-concordant care based on optimal anticoagulation, adequate rate control, management of co-morbidities and lifestyle measures. Associations between ABC-concordance and outcomes were assessed with adjustment for components of the CHA2DS2-VASc and HAS-BLED scores. Of 20 926 patients, 7915 (37.8%) satisfied criteria of ABC-concordant care, which was associated with significantly lower incidence of stroke or systemic embolic event [stroke/SEE: hazard ratio (HRadj): 0.54; 95% confidence interval (CI): 0.47-0.63], major bleeding (HRadj 0.66; 95% CI: 0.58-0.75), major adverse cardiac events (HRadj 0.53; 95% CI: 0.48-0.58), primary net clinical outcome (composite of stroke/SEE, major bleeding or death; HRadj 0.61; 95% CI: 0.56-0.65), cardiovascular (CV) hospitalization (HRadj 0.78; 95% CI: 0.74-0.83), CV death (HRadj 0.52; 95% CI: 0.46-0.58), and all-cause mortality (HRadj 0.56; 95% CI: 0.51-0.62), P < 0.001 for each. These associations were qualitatively consistent for both edoxaban and warfarin and across patient subgroups. CONCLUSION: Atrial fibrillation Better Care pathway-concordant care is associated with reductions across multiple CV endpoints and all-cause mortality, with benefit in edoxaban- and warfarin-treated patients and across patient subgroups. Increasing implementation of ABC-concordant care may improve clinical outcomes of patients with AF irrespective of anticoagulant.

Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor.

Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.

Predicting a late positive serum troponin in initially troponin-negative patients with non-ST-elevation acute coronary syndrome: clinical predictors and validated risk score results from the TIMI IIIB and GUSTO IIA studies.

BACKGROUND: Troponin testing is useful for evaluating patients with non-ST-segment elevation acute coronary syndromes (NSTE ACS); however, a significant percentage of patients are troponin negative at presentation and develop late rise of the marker. METHODS: Patients in the TIMI IIIB study were assessed with respect to their troponin I (TnI) status at presentation and 12 hours. Multivariable analysis identified independent clinical factors associated with TnI rise at 12 hours among subjects initially TnI negative. A score predicting late TnI rise in TIMI IIIB was developed using these factors and validated among patients in the GUSTO IIA study. RESULTS: Of 1342 subjects in TIMI IIIB, 200 (14.9%) were negative at baseline, but developed an elevated TnI (> or = 0.4 ng/mL) at 12 hours. Six independent predictors of late TnI rise were identified: ST-segment deviation (odds ratio [OR] 3.52, 95% CI 2.38-5.23, P < .001), presentation < 8 hours from symptom onset (OR 2.91, 95% CI 1.92-4.40, P < .001), no prior percutaneous coronary intervention (OR 2.88, 95% CI 1.54-5.39, P = .001), no prior beta-blocker use (OR 1.74, 95% CI 1.15-2.63, P = .008), unheralded angina (OR 1.65, 95% CI 1.12-2.42, P = .01), and a history of myocardial infarction (OR 1.59, 95% CI 1.06-2.37, P = .02). ST deviation, presentation < 8 hours from symptoms, and no prior percutaneous coronary intervention were given a score of 2 points, whereas a score of 1 point was assigned to the other factors. Among baseline TnI-negative patients, a rising score was paralleled by an increasing prevalence of late TnI rise from 0% (with a score of 0) to 69% (with a score of 9) (P < .001). In confirmation, the score was able to similarly predict late troponin T rise among 855 patients in the GUSTO IIA study (P < .0001). CONCLUSION: Development of late troponin rise is common in non-ST-segment elevation acute coronary syndromes. Six easily ascertained variables may be used to identify those at higher risk for late rise in troponin levels after an initially negative presentation.

Angiographic and clinical outcomes associated with direct versus conventional stenting among patients treated with fibrinolytic therapy for ST-elevation acute myocardial infarction.

The present study reports outcomes of direct stenting versus conventional stenting, which was performed during adjunctive/rescue percutaneous coronary intervention (n = 556) in the Integrilin and Tenecteplase in Acute Myocardial Infarction trial, the Enoxaparin as Adjunctive Antithrombin Therapy for ST-Elevation Myocardial Infarction-Thrombolysis in Myocardial Infarction 23 trial, and the Fibrinolytic and Aggrastat ST-Elevation Resolution trial of fibrinolytic therapy in ST-elevation myocardial infarction. Direct stenting was associated with a lower rate of death, myocardial infarction, or congestive heart failure during hospitalization and at 30 days and was independently associated with improved in-hospital outcomes (odds ratio 0.44, 95% confidence interval 0.23 to 0.85, p = 0.014).

Prasugrel versus clopidogrel in patients with ST-segment elevation myocardial infarction according to timing of percutaneous coronary intervention: a TRITON-TIMI 38 subgroup analysis (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38).

OBJECTIVES: This study sought to evaluate the efficacy of prasugrel versus clopidogrel in ST-segment elevation myocardial infarction (STEMI) by the timing of percutaneous coronary intervention (PCI). BACKGROUND: Treatment strategies and outcomes for patients with STEMI may differ when treated with primary compared with secondary PCI. METHODS: STEMI patients in the TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis In Myocardial Infarction 38) were randomized to prasugrel or clopidogrel on presentation if primary PCI was intended or later during secondary PCI. Primary PCI was defined as within 12 h of symptom onset. The primary endpoint was cardiovascular death, myocardial infarction (MI), or stroke. Because periprocedural MI is difficult to assess in the setting of STEMI, we performed analyses excluding these events. RESULTS: Reductions in the primary endpoint with prasugrel versus clopidogrel (hazard ratio [HR]: 0.79; 95% confidence interval [CI]: 0.65 to 0.97; p = 0.022) were consistent between primary and secondary PCI patients at 15 months (HR: 0.89; 95% CI: 0.69 to 1.13 vs. HR: 0.65; 95% CI: 0.46 to 0.93; p interaction = 0.15). However, a tendency toward a difference in treatment effect at 30 days (HR: 0.68; 95% CI: 0.54 to 0.87; p = 0.002) was observed between primary and secondary PCI patients (HR: 0.81; 95% CI: 0.60 to 1.09 vs. HR: 0.51; 95% CI: 0.34 to 0.76; p interaction = 0.06). When periprocedural MI was excluded, the efficacy of prasugrel remained consistent among primary and secondary PCI patients at 30 days (HR: 0.53; 95% CI: 0.34 to 0.81 vs. HR: 0.44; 95% CI: 0.22 to 0.88; p interaction = 0.68) and 15 months (HR: 0.76; 95% CI: 0.56 to 1.03 vs. HR: 0.75; 95% CI: 0.46 to 1.21; p interaction = 0.96). CONCLUSIONS: The efficacy of prasugrel versus clopidogrel was consistent irrespective of the timing of PCI, particularly in preventing nonprocedural events. (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel-Thrombolysis in Myocardial Infarction 38; NCT00097591).

Relation between time of symptom onset of ST-segment elevation myocardial infarction and patient baseline characteristics: from the National Cardiovascular Data Registry.

BACKGROUND: The presence of a morning excess of ST-segment elevation myocardial infarction (STEMI) has been observed. The relation between patient characteristics and timing of STEMI may provide insight into the biological processes responsible for this phenomenon. HYPOTHESIS: Patient baseline characteristics will vary with timing of STEMI. METHODS: We performed an analysis using a large national registry of unselected patients with STEMI (N=45,218). Patients were categorized by time of symptom onset: early (6 am-2 pm), late day (2 pm-10 pm), and overnight (10 pm-6 am) then evaluated for variations in characteristics. RESULTS: A circadian variation in the timing of symptom onset of STEMI was observed (early 41%, late day 32%, and overnight 26%, P<0.001). Circadian variations in factors known to alter timing of events were seen, including lower rates of home ß-blocker use, smoking, and diabetes, with early onset of STEMI symptoms. In addition, patients in the 6 am to 2 pm subgroup were more likely older, white race, and male, with higher rates of home aspirin use and lower rates of obesity. Higher rates of coexisting cardiovascular disease, including prior heart failure, 3-vessel coronary artery disease, and depressed left ventricular ejection fraction, were observed in the overnight group. More robust antiplatelet therapy with home clopidogrel use was not associated with a change in the timing of events. CONCLUSIONS: A morning excess of STEMI continues to exist and represents a potential target for preventative strategies. Patient baseline characteristics vary with the onset of STEMI and may reflect a physiologic relationship between these factors and the timing of events.

Comparative cost-effectiveness of interventions to improve medication adherence after myocardial infarction.

OBJECTIVE: To evaluate the comparative cost-effectiveness of interventions to improve adherence to evidence-based medications among postmyocardial infarction (MI) patients. DATA SOURCES/STUDY SETTING: Cost-effectiveness analysis. STUDY DESIGN: We developed a Markov model simulating a hypothetical cohort of 65-year-old post-MI patients who were prescribed secondary prevention medications. We evaluated mailed education, disease management, polypill use, and combinations of these interventions. The analysis was performed from a societal perspective over a lifetime horizon. The main outcome was an incremental cost-effectiveness ratio (ICER) as measured by cost per quality-adjusted life year (QALY) gained. DATA COLLECTION/EXTRACTION METHODS: Model inputs were extracted from published literature. PRINCIPAL FINDINGS: Compared with usual care, only mailed education had both improved health outcomes and reduced spending. Mailed education plus disease management, disease management, polypill use, polypill use plus mailed education, and polypill use plus disease management cost were $74,600, $69,200, $133,000, $113,000, and $142,900 per QALY gained, respectively. In an incremental analysis, only mailed education had an ICER of less than $100,000 per QALY and was therefore the optimal strategy. Polypill use, particularly when combined with mailed education, could be cost effective, and potentially cost saving if its price decreased to less than $100 per month. CONCLUSIONS: Mailed education and a polypill, once available, may be the cost-saving strategies for improving post-MI medication adherence.

El magnesio en el tratamiento del infarto agudo del miocardio. Revisión y controversias / Magnesium in the treatment of acute myocardial infraction

La utilización del magnesio en el tratamiento del infarto agudo del miocardio es motivo de controversia, pues su aplicación rutinaria no es una práctica establecida. Hay bases fisiológicas que atribuyen al magnesio propiedades de protección miocárdica sobre todo en relación con la terapia de reperfusión. En este trabajo se analizan los aspectos básicos del metabolismo del magnesio y sus efectos en el sistema cardiovascular, así como los efectos benéficos de este catión: en la prevención de arritmias, efectos antiplaquetarios, vasodilatación coronaria y prevención del daño por reperfusión, así mismo los riesgos de su aplicación en la cardiopatía isquémica. Ya que los resultados en los principales estudios han originado debate, se señalan las principales diferencias entre estos estudios y cuales son las posibles explicaciones al respecto y que dan como consecuencia diferencia en la interpretación de los hallazgos.