Impact of hemoglobin levels at admission on outcomes among elderly patients with acute coronary syndrome treated with low-dose Prasugrel or clopidogrel: A sub-study of the ELDERLY ACS 2 trial.

Hemoglobin (Hb) levels have emerged as a useful tool for risk stratification and the prediction of outcome after myocardial infarction. We aimed at evaluating the prognostic impact of this parameter among patients in advanced age, where the larger prevalence of anemia and the higher rate of comorbidities could directly impact on the cardiovascular risk. METHODS: All the patients in the ELDERLY-2 trial, were included in this analysis and stratified according to the values of hemoglobin at admission. The primary endpoint of this study was cardiovascular mortality within one year. The secondary endpoints were all-cause mortality, MI, Bleeding Academic Research Consortium (BARC) type 2-3 or 5 bleeding, any stroke, re-hospitalization for cardiovascular event or stent thrombosis (probable or definite) within 12 months after index admission. RESULTS: We included in our analysis 1364 patients, divided in quartiles of Hb values (<12.2; 12.2-13.39; 13.44-14.49; ≥ 4.5 g/dl). At a mean follow- up of 330.4 ± 99.9 days cardiovascular mortality was increased in patients with lower Hb (HR[95%CI] = 0.76 [0.59-0.97], p = 0.03). Results were no more significant after correction for baseline differences (adjusted HR[95%CI] = 1.22 [0.41-3.6], p = 0.16). Similar results were observed for overall mortality. At subgroup analysis, (according to Hb median values) a significant interaction was observed only with the type of antiplatelet therapy, but not with major high-risk subsets of patients. CONCLUSIONS: Among elderly patients with acute coronary syndrome managed invasively, lower hemoglobin at admission is associated with higher cardiovascular and all-cause mortality and major ischemic events, mainly explained by the higher risk profile.

Residual SYNTAX Score and One-Year Outcome in Elderly Patients With Acute Coronary Syndrome.

BACKGROUND: The residual burden of coronary artery disease after percutaneous coronary intervention (PCI) has been associated with worse ischemic outcome. However, data are conflicting in elderly patients. The aim of our study was to verify the incremental value of the residual Synergy Between Percutaneous Coronary Intervention With Taxus and Cardiac Surgery (SYNTAX) score (rSS) over clinical variables and baseline SYNTAX score (bSS) in predicting 1-year mortality or cardiovascular events. METHODS: A post hoc analysis of data collected in the Elderly-ACS 2 multicenter randomized trial was performed. We included 630 patients aged > 75 years with multivessel coronary disease undergoing PCI for acute coronary syndrome (ACS). The primary outcome was a composite of death, recurrent myocardial infarction, and stroke at 1-year follow up. Change in c-statistic and standardized net benefit were used to evaluate the incremental value of the rSS. RESULTS: Event rates were significantly higher in patients with incomplete revascularization (rSS > 8). When the rSS was included in a core Cox regression model containing age, previous myocardial infarction, and ACS type, the hazard ratio for patients with score values > 8 was 2.47 (95% confidence interval, 1.51-4.06). However, the core model with rSS did not increase the c-statistic compared with the core model with the bSS (from 0.69 to 0.70) and gave little incremental value in the standardized net benefit. CONCLUSIONS: In elderly patients with ACS with multivessel disease undergoing PCI, incomplete revascularization was associated with worse outcome at 1-year follow-up. However, there was no clear incremental value of the rSS in the prediction of 1-year adverse outcome compared with a model including clinical variables and bSS.

CONTEXTE: Le fardeau résiduel de la coronaropathie après une intervention coronarienne percutanée (ICP) a été associé à de moins bons résultats sur le plan ischémique. Les données recueillies chez les patients âgés sont toutefois contradictoires. Cette étude avait donc pour objectif de valider la valeur ajoutée du score SYNTAX (SYNergy between percutaneous coronary intervention with TAXus and cardiac surgery) résiduel (SSr) par rapport aux paramètres cliniques et au score SYNTAX initial (SSi) pour prédire la mortalité à 1 an et les manifestations cardiovasculaires. MÉTHODOLOGIE: Une analyse a posteriori des données de l'étude multicentrique avec répartition aléatoire Elderly-ACS 2 a été effectuée. Pour ce faire, 630 patients âgés de plus de 75 ans, atteints d'une coronaropathie multitronculaire et ayant subi une ICP pour traiter un syndrome coronarien aigu (SCA) ont été retenus. Le critère d'évaluation principal était composé du décès, de l'infarctus du myocarde récurrent et de l'accident vasculaire cérébral (AVC) au moment du suivi à 1 an. La variation de la statistique C et le bénéfice net normalisé ont servi à évaluer la valeur ajoutée du SSr. RÉSULTATS: Les manifestations étaient significativement plus fréquentes chez les patients dont la revascularisation était incomplète (SSr > 8). Lorsque le SSr a été pris en compte dans un modèle de régression de Cox de base ayant pour facteurs l'âge, les antécédents d'infarctus du myocarde et le type de SCA, le rapport des risques instantanés pour les patients ayant un score > 8 était de 2,47 (intervalle de confiance à 95 % : 1,51-4,06). L'intégration du SSr dans le modèle de base n'a toutefois pas donné lieu à une statistique C plus élevée que celle du SSi (0,70 vs 0,69) et conférait peu de valeur ajoutée sur le plan du bénéfice net normalisé. CONCLUSIONS: Chez les patients âgés présentant un SCA et une atteinte multitronculaire, et subissant une ICP, la revascularisation incomplète a été associée à de moins bons résultats au moment du suivi à 1 an. Le SSr n'a toutefois pas été clairement associé à une valeur ajoutée pour prédire une issue défavorable à 1 an comparativement à un modèle reposant sur des paramètres cliniques et le SSi.

Impact of diabetes on clinical outcome among elderly patients with acute coronary syndrome treated with percutaneous coronary intervention: insights from the ELDERLY ACS 2 trial.

BACKGROUND: Despite recent improvements in percutaneous coronary revascularization and antithrombotic therapies for the treatment of acute coronary syndromes, the outcome is still unsatisfactory in high-risk patients, such as the elderly and patients with diabetes. The aim of the current study was to investigate the prognostic impact of diabetes on clinical outcome among patients included in the Elderly-ACS 2 trial, a randomized, open-label, blinded endpoint study carried out at 32 centers in Italy. METHODS: Our population is represented by 1443 patients included in the Elderly-ACS 2 trial. Diabetes was defined as known history of diabetes at admission. The primary endpoint of this analysis was cardiovascular mortality, while secondary endpoints were all-cause death, recurrent myocardial infarction, Bleeding Academic Research Consortium type 2 or 3 bleeding, and rehospitalization for cardiovascular event or stent thrombosis within 12 months after index admission. RESULTS: Diabetes was present in 419 (29%) out of 1443 patients. Diabetic status was significantly associated with major cardiovascular risk factors and history of previous coronary disease, presentation with non-ST segment elevation myocardial infarction (P = 0.01) more extensive coronary disease (P = 0.02), more advanced Killip class at presentation (P = 0.003), use at admission of statins (P = 0.004) and diuretics at discharge (P < 0.001). Median follow-up was 367 days (interquartile range: 337-378 days). Diabetic status was associated with an absolute increase in the rate of cardiovascular mortality as compared with patients without diabetes [5.5 vs. 3.3%, hazard ratio (HR) 1.7 (0.99-2.8), P = 0.054], particularly among those treated with clopidogrel [HR (95% confidence interval (CI)) = 1.89 (0.93-3.87), P = 0.08]. However, this difference disappeared after correction for baseline differences [Adjusted HR (95% CI) 1.1(0.4-2.9), P = 0.86]. Similar findings were observed for other secondary endpoints, except for bleeding complications, significantly more frequent in diabetic patients [HR (95% CI) 2.02 (1.14-3.6), P = 0.02; adjusted HR (95% CI) = 2.1 (1.01-4.3), P = 0.05]. No significant interaction was observed between type of dual antiplatelet therapy, diabetic status and outcome. CONCLUSION: Among elderly patients with acute coronary syndromes, diabetic status was associated with higher rates of comorbidities, more severe cardiovascular risk profile and major bleeding complications fully accounting for the absolute increase in mortality. In fact, diabetes mellitus did not emerge as an independent predictor of survival in advanced age.

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 (

Outcomes of Elderly Patients with ST-Elevation or Non-ST-Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

INTRODUCTION: Acute coronary syndromes (ACS) have been classified according to the finding of ST-segment elevation on the presenting electrocardiogram, with different treatment strategies and practice guidelines. However, a comparative description of the clinical characteristics and outcomes of acute coronary syndrome elderly patients undergoing percutaneous coronary intervention during index admission has not been published so far. METHODS: Retrospective cohort study of patients enrolled in the Elderly ACS-2 multicenter randomized trial. Main outcome measures were crude cumulative incidence and cause-specific hazard ratio (cHR) of cardiovascular death, noncardiovascular death, reinfarction, and stroke. RESULTS: Of 1443 ACS patients aged >75 years (median age 80 years, interquartile range 77-84), 41% were classified as ST-elevation myocardial infarction (STEMI), and 59% had non-ST-elevation ACS (NSTEACS) (48% NSTEMI and 11% unstable angina). As compared with those with NSTEACS, STEMI patients had more favorable baseline risk factors, fewer prior cardiovascular events, and less severe coronary disease, but lower ejection fraction (45% vs 50%, P < .001). At a median follow-up of 12 months, 51 (8.6%) STEMI patients had died, vs 39 (4.6%) NSTEACS patients. After adjusting for sex, age, and previous myocardial infarction, the hazard among the STEMI group was significantly higher for cardiovascular death (cHR 1.85; 95% confidence interval [CI], 1.02-3.36), noncardiovascular death (cHR 2.10; 95% CI, 1.01-4.38), and stroke (cHR 4.8; 95% CI, 1.7-13.7). CONCLUSIONS: Despite more favorable baseline characteristics, elderly STEMI patients have worse survival and a higher risk of stroke compared with NSTEACS patients after percutaneous coronary intervention.

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.

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).

Major rectus abdominis hematoma complicating low molecular weight heparin therapy.

The use of low molecular weight heparin sometimes leads to major life threatening complications, such as acute abdominal haemorrhages. We report two cases of major haematoma of rectus abdominis. Computed tomography was very helpful to confirm the diagnosis in these cases.