Abstract Background Elderly patients display higher on clopidogrel platelet reactivity as compared to younger patients. Treatment with prasugrel 5 mg has been shown to provide more predictable and ...homogenous antiplatelet effect, as compared to 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 75 mg in patients >74 years of age with ACS (either ST- or non ST-elevation myocardial infarction) undergoing early percutaneous revascularization. The primary endpoint is the composite of all-cause mortality, myocardial re-infarction, disabling stroke and re-hospitalization for cardiovascular causes or bleeding within one year. Taking advantage of the planned size of 2000 patients, the secondary objective is to assess the prognostic impact of selected pre-randomization variables (age, sex, diabetic status, serum creatinine level, ECG 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 )
The Italian Elderly ACS study was the first randomized controlled trial comparing an early aggressive with an initially conservative strategy in patients with non–ST-segment elevation acute coronary ...syndromes aged ≥75 years, with the results showing no significant benefit of early aggressive therapy. The aim of this study was to evaluate the outcomes of trial patients, according to the treatment actually received during hospitalization. The trial enrolled 313 patients. The primary end point was the composite of death, myocardial infarction (MI), disabling stroke, and repeat hospital stay for cardiovascular causes or bleeding within 1 year. All patients in whom coronary angiography was performed during initial hospitalization were defined as having undergone invasive treatment (182 patients), whereas all patients who did not undergo coronary angiography were classified as medically managed (conservative treatment CT group, 131 patients). The primary end point occurred in 53 patients (40.5%) in the CT group and 45 patients (24.7%) in the invasive treatment group (hazard ratio 0.56, 95% confidence interval 0.37 to 0.83, p = 0.003). The invasive treatment group showed significantly lower rates of MI (6% vs 13% in the CT group; hazard ratio 0.43, 95% confidence interval 0.20 to 0.92, p = 0.034) and the aggregate of death and MI (14.3% vs 27.5% CT group; hazard ratio 0.48, 95% confidence interval 0.29 to 0.81, p = 0.004). In conclusion, elderly patients with non–ST-segment elevation acute coronary syndromes treated invasively experienced significantly better survival free from the composite of all-cause mortality, nonfatal MI, disabling stroke, and repeat hospitalization for cardiovascular causes or bleeding.
Background The role of emergency reperfusion therapy in patients with ST-elevation myocardial infarction (STEMI) resuscitated after an out-of-hospital cardiac arrest (OHCA) has not been clearly ...established yet. The aim of this study was to evaluate the in-hospital and postdischarge outcomes of STEMI patients surviving OHCA and undergoing emergency angioplasty (percutaneous coronary intervention PCI) within an established regional network. Methods We prospectively collected data on 2,617 consecutive patients with STEMI treated with emergency PCI in 2005; in-hospital and 6-month outcomes of 99 patients who had experienced OHCA were compared with those of 2,518 patients without OHCA. The OHCA patients also underwent a cerebral performance evaluation after 12 months. Results OHCA patients were at higher clinical risk at presentation (cardiogenic shock 26% vs 5%, P < .0001). Percutaneous coronary intervention was successful in 80% of the OHCA and 89% of the non-OHCA patients ( P = NS). In-hospital mortality rates were 22% and 3%, respectively ( P < .0001). Independent predictors of in-hospital mortality among OHCA patients were longer delay between the call to the emergency medical system and the start of cardiopulmonary resuscitation (odds ratio OR 3.5, P = .03), nonshockable initial rhythms (OR 10.5, P = .002), cardiogenic shock (OR 3.05, P = .035), and a Glasgow Coma Scale score of 3 on admission (OR 2.9, P = .032). The 6-month composite rate of death, myocardial infarction, and revascularization among OHCA patients surviving the acute phase was comparable to that of non-OHCA patients (16% vs 13.9%, P = NS), and 87% of them showed a favorable neurologic recovery after 1 year. Conclusions Resuscitated OHCA patients undergoing emergency PCI for STEMI have worse clinical presentation and higher in-hospital mortality compared to those without OHCA. However, subsequent cardiac events are similar, and neurologic recovery is more favorable than reported in most previous series.
Approximately 1/3 of patients with non–ST-segment elevation (NSTE) acute coronary syndromes (ACS) are ≥75 years of age. Risk stratification in these patients is generally difficult because supporting ...evidence is scarce. The investigators developed and validated a simple risk prediction score for 1-year mortality in patients ≥75 years of age presenting with NSTE ACS. The derivation cohort was the Italian Elderly ACS trial, which included 313 patients with NSTE ACS aged ≥75 years. A logistic regression model was developed to predict 1-year mortality. The validation cohort was a registry cohort of 332 patients with NSTE ACS meeting the same inclusion criteria as for the Italian Elderly ACS trial but excluded from the trial for any reason. The risk score included 5 statistically significant covariates: previous vascular event, hemoglobin level, estimated glomerular filtration rate, ischemic electrocardiographic changes, and elevated troponin level. The model allowed a maximum score of 6. The score demonstrated a good discriminating power (C statistic = 0.739) and calibration, even among subgroups defined by gender and age. When validated in the registry cohort, the scoring system confirmed a strong association with the risk for all-cause death. Moreover, a score ≥3 (the highest baseline risk group) identified a subset of patients with NSTE ACS most likely to benefit from an invasive approach. In conclusion, the risk for 1-year mortality in patients ≥75 years of age with NSTE ACS is substantial and can be predicted through a score that can be easily derived at the bedside at hospital presentation. The score may help in guiding treatment strategy.
The causes of death within 1 year of hospital admission in patients with non–ST-segment elevation acute coronary syndromes are ill defined, particularly in patients aged ≥75 years. From January 2008 ...through May 2010, we enrolled 645 patients aged ≥75 years with non–ST-segment elevation acute coronary syndromes: 313 in a randomized trial comparing an early aggressive versus an initially conservative approach, and 332, excluded from the trial for specific reasons, in a parallel registry. Each death occurring during 1 year of follow-up was adjudicated by an independent committee. The mean age was 82 years in both study cohorts, and 53% were men. By the end of the follow-up period (median 369 days, interquartile range 345 to 391), 120 patients (18.6%) had died. The mortality was significantly greater in the registry (23.8% vs 13.1%, p = 0.001). The deaths were classified as cardiac in 94% of the cases during the index admission and 68% of the cases during the follow-up period. Eighty-six percent of the cardiac deaths were of ischemic origin. In a multivariate logistic regression model that included the variables present on admission in the whole study population, the ejection fraction (hazard ratio 0.95, 95% confidence interval 0.94 to 0.97; p <0.001), hemoglobin level (hazard ratio 0.85, 95% confidence interval 0.76 to 0.94; p = 0.001), older age (hazard ratio 1.05, 95% confidence interval 1.01 to 1.10, p = 0.010), and creatinine clearance (hazard ratio 0.99, 95% confidence interval 0.97 to 0.99; p = 0.030) were the independent predictors of all-cause death at 1 year. In conclusion, within 1 year after admission for non–ST-segment elevation acute coronary syndromes, most deaths in patients aged ≥75 years have a cardiac origin, mostly owing to myocardial ischemia.
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.
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.
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.
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.
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.
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.
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.
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.
Background In acute myocardial infarction complicated by cardiogenic shock (CS), up to 80% of patients present with multivessel coronary artery disease. Currently, the best revascularization strategy ...is unknown. Therefore, a prospective randomized adequately powered clinical trial is warranted. Study design The CULPRIT-SHOCK study is a 706-patient controlled, international, multicenter, randomized, open-label trial. It is designed to compare culprit lesion only percutaneous coronary intervention (PCI) with possible staged non-culprit lesion revascularization versus immediate multivessel PCI in patients with CS complicating acute myocardial infarction. Patients will be randomized in a 1:1 fashion to one of the two treatment arms. The primary efficacy endpoint of CULPRIT-SHOCK is 30-day mortality and severe renal failure requiring renal replacement therapy. Secondary outcome measures such as hemodynamic, laboratory, and clinical parameters will serve as surrogate endpoints for prognosis. Furthermore, an intermediate- and long-term follow-up at 6 and 12 months will be performed. Safety endpoints include the assessment of bleeding and stroke. Conclusions The CULPRIT-SHOCK trial will address the question of optimal revascularization strategy in patients with multivessel disease and acute myocardial infarction complicated by CS.
Summary Background Thrombolysis remains the treatment of choice in ST-segment elevation myocardial infarction (STEMI) when primary percutaneous coronary intervention (PCI) cannot be done within 90 ...min. However, the best subsequent management of patients after thrombolytic therapy remains unclear. To assess the best management, we randomised patients with STEMI treated by thrombolysis and abciximab at a non-interventional hospital to immediate transfer for PCI, or to standard medical therapy with transfer for rescue angioplasty. Methods 600 patients aged 75 years or younger with one or more high-risk features (extensive ST-segment elevation, new-onset left bundle branch block, previous myocardial infarction, Killip class >2, or left ventricular ejection fraction ≤35%) in hospitals in France, Italy, and Poland were treated with half-dose reteplase, abciximab, heparin, and aspirin, and randomly assigned to immediate transfer to the nearest interventional centre for PCI, or to management in the local hospital with transfer only in case of persistent ST-segment elevation or clinical deterioration. The primary outcome was a composite of death, reinfarction, or refractory ischaemia at 30 days, and analysis was by intention to treat. This study is registered with ClinicalTrials.gov , number 00220571. Findings Of the 299 patients assigned to immediate PCI, 289 (97·0%) underwent angiography, and 255 (85·6%) received PCI. Rescue PCI was done in 91 patients (30·3%) in the standard care/rescue PCI group. The primary outcome occurred in 13 patients (4·4%) in the immediate PCI group compared with 32 (10·7%) in the standard care/rescue PCI group (hazard ratio 0·40; 95% CI 0·21–0·76, log rank p=0·004). Major bleeding was seen in ten patients in the immediate group and seven in the standard care/rescue group (3·4% vs 2·3%, p=0·47). Strokes occurred in two patients in the immediate group and four in the standard care/rescue group (0·7% vs 1·3%, p=0·50). Interpretation Immediate transfer for PCI improves outcome in high-risk patients with STEMI treated at a non-interventional centre with half-dose reteplase and abciximab.
Abstract Objectives This study sought to investigate sex-related differences in treatment and outcomes in elderly patients with non–ST-segment elevation acute coronary syndromes (NSTEACS). Background ...Female sex and older age are usually associated with worse outcome in NSTEACS. The Italian Elderly ACS study enrolled NSTEACS patients aged 75 years of age and older in a randomized trial comparing an early aggressive with an initially conservative strategy and in a registry of patients with ≥1 exclusion criteria of the trial. Methods We compared sexes in the pooled populations of the trial and registry. Results A total of 645 patients (313 from the trial and 332 from the registry), including 301 women (47%), were enrolled. Women were slightly older than men (82.1 ± 5.0 years vs. 81.2 ± 4.5 years; p = 0.02), had lower hemoglobin levels (12.5 ± 1.6 g/dl vs. 13.3 ± 1.9 g/dl; p < 0.001), and underwent fewer coronary revascularizations during the index admission (37.2% vs. 45.0%; p = 0.04). In-hospital adverse event rates were similar in both sexes; severe bleeding was uncommon (0.3% vs. 0%). The 1-year primary endpoint (composite of death, nonfatal myocardial infarction, disabling stroke, cardiac rehospitalization, and severe bleeding) occurred less often in women (27.6% vs. 38.7%; p < 0.01). Women not undergoing revascularization showed a 3-fold higher mortality, both in-hospital (8.5% vs. 2.7%; p = 0.05) and at 1 year (21.6% vs. 8.1%; p = 0.002). Conclusions Elderly women had a similar in-hospital outcome and better 1-year outcome compared with men. Coronary revascularization in women was associated with lower 1-year mortality, without an increase in severe bleeding. Elderly women with NSTEACS should always be considered for early revascularization.
Abstract Background Worsening renal function during hospitalization for an acute coronary syndrome is strongly predictive of in-hospital and long-term outcome. However, the role of post-discharge ...worsening renal function has never been investigated in this setting. Methods We considered the placebo cohort of the AleCardio trial comparing aleglitazar with standard medical therapy among patients with type 2 diabetes mellitus and a recent acute coronary syndrome. Patients who had died or had been admitted to hospital for heart failure before the 6-month follow-up, as well as patients without complete renal function data, were excluded, leaving 2776 patients for the analysis. Worsening renal function was defined as a >20% reduction in estimated glomerular filtration rate from discharge to 6 months, or progression to macroalbuminuria. The Cox regression analysis was used to determine the prognostic impact of 6-month renal deterioration on the composite of all-cause death and hospitalization for heart failure. Results Worsening renal function occurred in 204 patients (7.34%). At a median follow-up of 2 years the estimated rates of death and hospitalization for heart failure per 100 person-years were 3.45 (95% confidence interval CI, 2.46-6.36) for those with worsening renal function, versus 1.43 (95% CI, 1.14-1.79) for patients with stable renal function. At the adjusted analysis worsening renal function was associated with the composite endpoint (hazard ratio 2.65; 95% CI, 1.57-4.49; P <.001). Conclusions Post-discharge worsening renal function is not infrequent among patients with type 2 diabetes and acute coronary syndromes with normal or mildly depressed renal function, and is a strong predictor of adverse cardiovascular events.
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