Impact of body mass index on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: Insights from the ELDERLY ACS 2 trial.

BACKGROUND AND AIM: Elderly patients are at increased risk of hemorrhagic and thrombotic complications after an acute coronary syndrome (ACS). Frailty, comorbidities and low body weight have emerged as conditioning the prognostic impact of dual antiplatelet therapy (DAPT). The aim of the present study was to investigate the prognostic impact of body mass index (BMI) on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study comparing low-dose (5 mg) prasugrel vs clopidogrel among elderly patients with ACS. METHODS AND RESULTS: Our population is represented by 1408 patients enrolled in the Elderly-ACS 2 trial. BMI was calculated at admission. The primary endpoint of this analysis was cardiovascular (CV) mortality. Secondary endpoints were all-cause death, recurrent MI, Bleeding Academic Research Consortium (BARC) type 2 or 3 bleeding, and re-hospitalization for cardiovascular reasons or stent thrombosis within 12 months after index admission. Patients were grouped according to median values of BMI (

Comparison of Reduced-Dose Prasugrel and Standard-Dose Clopidogrel in Elderly Patients With Acute Coronary Syndromes Undergoing Early Percutaneous Revascularization.

BACKGROUND: Elderly patients are at elevated risk of both ischemic and bleeding complications after an acute coronary syndrome and display higher on-clopidogrel platelet reactivity compared with younger patients. Prasugrel 5 mg provides more predictable platelet inhibition compared with clopidogrel in the elderly, suggesting the possibility of reducing ischemic events without increasing bleeding. METHODS: In a multicenter, randomized, open-label, blinded end point trial, we compared a once-daily maintenance dose of prasugrel 5 mg with the standard clopidogrel 75 mg in patients >74 years of age with acute coronary syndrome undergoing percutaneous coronary intervention. The primary end point was the composite of mortality, myocardial infarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. The study was designed to demonstrate superiority of prasugrel 5 mg over clopidogrel 75 mg. RESULTS: Enrollment was interrupted, according to prespecified criteria, after a planned interim analysis, when 1443 patients (40% women; mean age, 80 years) had been enrolled with a median follow-up of 12 months, because of futility for efficacy. The primary end point occurred in 121 patients (17%) with prasugrel and 121 (16.6%) with clopidogrel (hazard ratio, 1.007; 95% confidence interval, 0.78-1.30; P=0.955). Definite/probable stent thrombosis rates were 0.7% with prasugrel versus 1.9% with clopidogrel (odds ratio, 0.36; 95% confidence interval, 0.13-1.00; P=0.06). Bleeding Academic Research Consortium types 2 and greater rates were 4.1% with prasugrel versus 2.7% with clopidogrel (odds ratio, 1.52; 95% confidence interval, 0.85-3.16; P=0.18). CONCLUSIONS: The present study in elderly patients with acute coronary syndromes showed no difference in the primary end point between reduced-dose prasugrel and standard-dose clopidogrel. However, the study should be interpreted in light of the premature termination of the trial. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01777503.

Lights and shadows of long-term dual antiplatelet therapy in "real life" clinical scenarios.

Dual antiplatelet therapy (DAPT) is a cornerstone of treatment for patients with acute coronary syndromes (ACS). Mounting evidences have opened the debate about the optimal DAPT duration. Considering the ACS-pathophysiology, the most recent guidelines recommend DAPT in all ACS patients for at least 12 months unless there are contraindications such as excessive risk of bleeding. Thus, it can be considered acceptable earlier discontinuation if the risk of morbidity from bleeding outweighs the anticipated benefit. On the other hand, several studies have clearly indicated that a significant burden of platelet related-events, such as stroke and new ACS might occur after this period, suggesting that potential benefits might derive by prolonging DAPT beyond 12 months (Long DAPT). Indeed, although current guidelines give some indications about patients eligible for Long DAPT, they do not embrace several real-life clinical scenarios. Thus, in such scenarios, how to decide whether a patient is eligible for Long DAPT or not might be still challenging for clinicians. This position paper presents and discusses various "real-life" clinical scenarios in ACS patients, in order to propose several possible recommendations to overcome guidelines potential limitations.

A comparison of reduced-dose prasugrel and standard-dose clopidogrel in elderly patients with acute coronary syndromes undergoing early percutaneous revascularization: Design and rationale of the randomized Elderly-ACS 2 study.

BACKGROUND: Elderly patients display higher on clopidogrel platelet reactivity as compared with younger patients. Treatment with prasugrel 5mg has been shown to provide more predictable and homogenous antiplatelet effect, as compared with clopidogrel, suggesting the possibility of reducing ischemic events after an acute coronary syndrome (ACS) without increasing bleeding. STUDY DESIGN: The Elderly-ACS 2 study is a multicenter, randomized, parallel-group, open-label trial designed to demonstrate the superiority of a strategy of dual antiplatelet treatment using a reduced 5-mg daily dose of prasugrel over a standard strategy with a daily clopidogrel dose of 75mg in patients older than 74years with ACS (either ST- or non-ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary end point is the composite of all-cause mortality, myocardial reinfarction, disabling stroke, and rehospitalization for cardiovascular causes or bleeding within 1 year. Taking advantage of the planned size of 2,000 patients, the secondary objective is to assess the prognostic impact of selected prerandomization variables (age, sex, diabetic status, serum creatinine level, electrocardiogram changes, abnormal troponin levels, basal and residual SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery [SYNTAX] score). CONCLUSION: The Elderly-ACS 2 study is a multicenter, randomized trial comparing a strategy of dual antiplatelet therapy with a reduced dose of prasugrel with a standard dose of clopidogrel in elderly patients with ACS undergoing percutaneous revascularization (the Elderly ACS 2 trial: NCT01777503).

Preclinical manifestations of organ damage associated with the metabolic syndrome and its factors in outpatient children.

BACKGROUND: To evaluate whether the pediatric metabolic syndrome (MetS) or its factors are useful to detect subclinical abnormalities of cardiac, liver, and glomerular damage in an outpatient population. METHODS: The population study included 799 children (age 10 ± 3 years, mean ± SD), 24% of whom were normalweight, 25% overweight, and 51% obese. Alanine-aminotransferase (ALT) levels, estimated glomerular filtration rate (eGFR) and HOMA-IR were analyzed in all children. Microalbuminuria (MA) and left ventricular (LV) geometry and function were evaluated in 501 and 247 children, respectively. MetS was defined using Cook's criteria. RESULTS: MetS was diagnosed in 131 children (16%). Children with MetS+ and MetS- were similar for age, gender and Tanner stage distribution. Children with MetS+ showed higher ALT levels (31 ± 19 vs 21 ± 11 IU/L, p<0.0001), LV mass (39 ± 10 vs 34 ± 10 g/h(2.7), p<0.001) and relative wall thickness (0.37 ± 0.06 vs 0.35 ± 0.05, p<0.01) than MetS-. The two groups were similar for MA and eGFR. At multiple logistic regression analysis, children MetS+ showed a higher risk (OR, 95% Cl) adjusted for confounding factors, of high ALT levels (1.71, 1.12-2.59, p=0.012) and concentric LV hypertrophy (2.17, 1.01-4.66, p=0.047) than children MetS-. The risk of preclinical liver and cardiac damage associated with the MetS phenotype was not higher than predicted by its single components. CONCLUSIONS: Children with MetS show a 2-fold greater risk of having high ALT levels and concentric LV hypertrophy. However, the risk of subclinical manifestations of liver and cardiac damage can be predicted equally well by the single components of the syndrome.

Prehypertension in outpatient obese children.

BACKGROUND: The aim of the study was to analyze the prevalence of prehypertension (PH) in obese (OB) children and its relation with estimated glomerular filtration rate (eGFR) and left ventricular (LV) function. METHODS: The study included 447 OB and 131 normal-weight children. PH was defined according to the criteria proposed by the National High Blood Pressure Education Program Working Group on High Blood Pressure in Children and Adolescents. Insulin sensitivity was evaluated by HOMA(IR), and eGFR was calculated by Schwartz's formula. LV function was analyzed by echocardiography in 165 OB children. RESULTS: PH was observed in 79 OB children (17.7%) and in 2 (1.5%) controls. Among OB children, those with PH had greater percentage of males (P < 0.05), higher level of body mass index (BMI) (P < 0.001), waist circumference (WC) (P < 0.005), and HOMA(IR) (P < 0.001), compared to PH- children. The two groups did not differ for eGFR and LV function. At logistic regression analysis, PH was independently associated with male gender (P < 0.025) and HOMA(IR) (P < 0.002). Gender analysis showed that boys with PH presented higher levels of BMI (P < 0.005), WC (P < 0.01), HOMA(IR) (P < 0.001), and triglycerides (P < 0.005) compared to PH- boys. Females with PH were older and in more advanced postpubertal stage, had higher BMI, WC (P < 0.05, for all), and HOMA(IR) (P < 0.025), compared to PH- girls. CONCLUSIONS: In a population of outpatient OB children, the prevalence of PH was 17.7% and boys were more likely than girls to have PH. This condition is characterized by insulin resistance in both sexes but no impairment in glomerular and LV function.