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.

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.

Association of Sex with Outcome in Elderly Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

BACKGROUND: Worse outcomes have been reported for women, compared with men, after an acute coronary syndrome (ACS). Whether this difference persists in elderly patients undergoing similar invasive treatment has not been studied. We investigated sex-related differences in 1-year outcome of elderly acute coronary syndrome patients treated by percutaneous coronary intervention (PCI). METHODS: Patients 75 years and older successfully treated with PCI were selected among those enrolled in 3 Italian multicenter studies. Cox regression analysis was used to assess the independent predictive value of sex on outcome at 12-month follow-up. RESULTS: A total of 2035 patients (44% women) were included. Women were older and most likely to present with ST-elevation myocardial infarction (STEMI), diabetes, hypertension, and renal dysfunction; men were more frequently overweight, with multivessel coronary disease, prior myocardial infarction, and revascularizations. Overall, no sex disparity was found about all-cause (8.3% vs 7%, P = .305) and cardiovascular mortality (5.7% vs 4.1%, P = .113). Higher cardiovascular mortality was observed in women after STEMI (8.8%) vs 5%, P = .041), but not after non ST-elevation-ACS (3.5% vs 3.7%, P = .999). A sensitivity analysis excluding patients with prior coronary events (N = 1324, 48% women) showed a significantly higher cardiovascular death in women (5.4% vs 2.9%, P = .025). After adjustment for baseline clinical variables, female sex did not predict adverse outcome. CONCLUSIONS: Elderly men and women with ACS show different clinical presentation and baseline risk profile. After successful PCI, unadjusted 1-year cardiovascular mortality was significantly higher in women with STEMI and in those with a first coronary event. However, female sex did not predict cardiovascular mortality after adjustment for the different baseline variables.

Impact of renal dysfunction and acute kidney injury on outcome in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities. AIM: The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. METHODS: Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft-Gault formula ([(140-age) × body weight × 0.85 if female]/(72 × serum creatinine)* 1.73 m2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m2), moderate (eGFR 30-59 ml/min/1.73 m2) or severe (eGFR <30 ml/min/1.73 m2) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months. RESULTS: A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates (P < 0.001) of all-cause (4.5%, 7.5% and 17.8% in patients with none or mild, moderate and severe renal dysfunction, respectively) and cardiovascular mortality (2.8%, 5.2% and 10.2%, respectively). After multivariable adjustment, severe renal dysfunction was associated with a higher risk of all-cause (hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.52-5.37, P = 0.001) and cardiovascular death (HR 3.11, 95% CI 1.41-6.83, P = 0.005), whereas non-fatal events were unaffected. Acute kidney injury incidence was significantly higher in ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome patients (11.7% vs. 7.8%, P = 0.036) and in those with reduced baseline renal function (P < 0.001), and it was associated with increased mortality independently from baseline renal function and clinical presentation. CONCLUSIONS: Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality.

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 renal dysfunction and acute kidney injury on outcome in elderly patients with acute coronary syndrome undergoing percutaneous coronary intervention.

BACKGROUND: Chronic kidney disease is common in patients admitted with acute coronary syndrome and its prevalence dramatically increases with age. Understanding the determinants of adverse outcomes in this extremely high-risk population may be useful for the development of specific treatment strategies and planning of secondary prevention modalities. AIM: The aim of this study was to assess the impact of baseline renal function and acute kidney injury on one-year outcome of elderly patients with acute coronary syndrome treated with percutaneous coronary intervention. METHODS: Patients aged 75 years and older with acute coronary syndrome undergoing successful percutaneous coronary intervention were selected among those enrolled in three Italian multicentre studies. Based on the baseline estimated glomerular filtration rate (eGFR) calculated using the Cockcroft-Gault formula ([(140-age) × body weight × 0.85 if female]/(72 × serum creatinine)* 1.73 m2 of body surface area), patients were classified as having none or mild (eGFR ≥60 ml/min/1.73 m2), moderate (eGFR 30-59 ml/min/1.73 m2) or severe (eGFR <30 ml/min/1.73 m2) renal dysfunction. Acute kidney injury was defined according to the Acute Kidney Injury Network classification. All-cause and cardiovascular mortality, non-fatal myocardial infarction, rehospitalisation for cardiovascular causes, stroke and type 2, 3 and 5 Bleeding Academic Research Consortium bleedings were analysed up to 12 months. RESULTS: A total of 1904 patients were included. Of these, 57% had moderate and 11% severe renal dysfunction. At 12 months, patients with renal dysfunction had higher rates (P < 0.001) of all-cause (4.5%, 7.5% and 17.8% in patients with none or mild, moderate and severe renal dysfunction, respectively) and cardiovascular mortality (2.8%, 5.2% and 10.2%, respectively). After multivariable adjustment, severe renal dysfunction was associated with a higher risk of all-cause (hazard ratio (HR) 2.86, 95% confidence interval (CI) 1.52-5.37, P = 0.001) and cardiovascular death (HR 3.11, 95% CI 1.41-6.83, P = 0.005), whereas non-fatal events were unaffected. Acute kidney injury incidence was significantly higher in ST-elevation myocardial infarction versus non-ST-elevation acute coronary syndrome patients (11.7% vs. 7.8%, P = 0.036) and in those with reduced baseline renal function (P < 0.001), and it was associated with increased mortality independently from baseline renal function and clinical presentation. CONCLUSIONS: Baseline renal dysfunction is highly prevalent and is associated with higher mortality in elderly acute coronary syndrome patients undergoing percutaneous coronary intervention. Acute kidney injury occurs more frequently among ST-elevation myocardial infarction patients and those with pre-existing renal dysfunction and is independently associated with one-year mortality.

Immediate angioplasty versus standard therapy with rescue angioplasty after thrombolysis in the Combined Abciximab REteplase Stent Study in Acute Myocardial Infarction (CARESS-in-AMI): an open, prospective, randomised, multicentre trial.

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 < or =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.

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.

Predictors of mortality in hospital survivors with type 2 diabetes mellitus and acute coronary syndromes.

AIM: To define the predictors of long-term mortality in patients with type 2 diabetes mellitus and recent acute coronary syndrome. METHODS AND RESULTS: A total of 7226 patients from a randomized trial, testing the effect on cardiovascular outcomes of the dual peroxisome proliferator-activated receptor agonist aleglitazar in patients with type 2 diabetes mellitus and recent acute coronary syndrome (AleCardio trial), were analysed. Median follow-up was 2 years. The independent mortality predictors were defined using Cox regression analysis. The predictive information provided by each variable was calculated as percent of total chi-square of the model. All-cause mortality was 4.0%, with cardiovascular death contributing for 73% of mortality. The mortality prediction model included N-terminal proB-type natriuretic peptide (adjusted hazard ratio = 1.68; 95% confidence interval = 1.51-1.88; 27% of prediction), lack of coronary revascularization (hazard ratio = 2.28; 95% confidence interval = 1.77-2.93; 18% of prediction), age (hazard ratio = 1.04; 95% confidence interval = 1.02-1.05; 15% of prediction), heart rate (hazard ratio = 1.02; 95% confidence interval = 1.01-1.03; 10% of prediction), glycated haemoglobin (hazard ratio = 1.11; 95% confidence interval = 1.03-1.19; 8% of prediction), haemoglobin (hazard ratio = 1.01; 95% confidence interval = 1.00-1.02; 8% of prediction), prior coronary artery bypass (hazard ratio = 1.61; 95% confidence interval = 1.11-2.32; 7% of prediction) and prior myocardial infarction (hazard ratio = 1.40; 95% confidence interval = 1.05-1.87; 6% of prediction). CONCLUSION: In patients with type 2 diabetes mellitus and recent acute coronary syndrome, mortality prediction is largely dominated by markers of cardiac, rather than metabolic, dysfunction.

Renal dysfunction, coronary revascularization and mortality among elderly patients with non ST elevation acute coronary syndrome.

AIMS: To determine the association between baseline creatinine clearance (CrCl), coronary revascularization during index admission, and 1-year mortality in elderly patients with an acute coronary syndrome (ACS). METHODS AND RESULTS: We estimated CrCl using the Cockcroft-Gault (CG) formula in 313 patients aged ≥ 75 years enrolled in a prospective study of treatment strategies in non ST-elevation ACS (NSTEACS). Patients were stratified into four groups according to CrCl on admission (using a cutoff of 45 ml/min) and coronary revascularization versus medical management. The mean age of the study population was 81 years and the median serum creatinine level on admission was 1.0 mg/dl (interquartile range (IQR) 0.8-1.3). Patients with impaired renal function treated medically had higher in-hospital and 1-year mortality, especially if compared with patients with preserved renal function undergoing revascularization (1-year mortality 22.9% versus 4.9%). Across the spectrum of CrCl categories, coronary revascularization was independently associated with a lower risk of mortality (HR 0.405; 95% CI 0.174-0.940; p=0.035). CONCLUSIONS: In elderly patients with NSTEACS, coronary revascularization decreases the risk of 1-year death across each CrCl category, and is one of the most powerful predictors of 1-year outcome.

A risk score for predicting 1-year mortality in patients ≥75 years of age presenting with non-ST-elevation acute coronary syndrome.

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.

Acute Kidney Injury in Elderly Patients With Non-ST Elevation Acute Coronary Syndrome: Insights From the Italian Elderly: ACS Study.

We examined the incidence and predictors of acute kidney injury (AKI) in elderly patients (≥75 years) enrolled in the prospective Italian Elderly acute coronary syndrome (ACS) study and explored the impact of AKI on clinical outcome. Acute kidney injury, defined according to the Acute Kidney Injury Network criteria, occurred in 128 (21%) of 615 patients. Patients submitted to coronary angiographic procedures did not present higher rate of AKI. The only baseline variables independently associated with AKI development were creatinine clearance (odds ratio [OR]: 0.98; 95% confidence interval [CI]: 0.97-0.99) and left ventricular ejection fraction (OR: 0.98; 95% CI: 0.96-0.99). Adverse clinical events were significantly higher in patients who developed AKI. After multivariable adjustment, AKI (hazard ratio: 2.73; 95% CI: 1.87-4.0) was an independent predictor of all-cause mortality within 1 year.

Effect of an invasive strategy on outcome in patients ≥75 years of age with non-ST-elevation acute coronary syndrome.

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.

One-year mortality in elderly adults with non-ST-elevation acute coronary syndrome: effect of diabetic status and admission hyperglycemia.

OBJECTIVES: To determine whether type 2 diabetes mellitus and hyperglycemia on admission should be considered independent predictors of mortality in elderly adults with acute coronary syndrome (ACS). DESIGN: Prospective cohort study. SETTING: Twenty-three hospitals in Italy. PARTICIPANTS: Individuals aged 75 and older with non-ST-elevation ACS (NSTEACS) (mean age 82, 47% female) (N = 645). MEASUREMENTS: Diabetic status and blood glucose levels were assessed on admission. Hyperglycemia was defined as glucose greater than 140 mg/dL. Multivariable Cox proportional hazard regression was used to assess the potential confounding effect of major covariates on the association between diabetic status, admission glucose, and 1-year mortality. RESULTS: A history of diabetes mellitus was found in 231 participants (35.8%), whereas 257 (39.8%) had hyperglycemia. Hyperglycemia was found in 171 participants with diabetes mellitus (70%) and 86 (21%) without diabetes mellitus. Participants with diabetes mellitus were significantly (P < .05) more likely to have had prior myocardial infarction and stroke and had lower ejection fraction and blood hemoglobin. Hyperglycemia was associated with lower (P < .05) ejection fraction and estimated glomerular filtration rate (eGFR). Diabetic status and hyperglycemia were associated with greater 1-year mortality according to univariate analysis (54 participants with diabetes mellitus died (23.4%), versus 66 (15.9%) without diabetes mellitus (hazard ratio (HR) = 1.5 95% confidence interval (CI) = 1.0-2.1), and 60 participants with hyperglycemia died (23.3%), versus 60 (15.5%) without hyperglycemia (HR=1.6; 95% CI = 1.1-2.2), but this association was not statistically significant after adjustment for ejection fraction, age, blood hemoglobin, and eGFR. CONCLUSION: In elderly adults with NSTEACS, diabetes mellitus and hyperglycemia on admission are associated with higher mortality, mostly because of preexisting cardiovascular and renal damage.

Causes of death in patients ≥75 years of age with non-ST-segment elevation acute coronary syndrome.

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.

Timing of events in STEMI patients treated with immediate PCI or standard medical therapy: implications on optimisation of timing of treatment from the CARESS-in-AMI trial.

OBJECTIVES: Early angioplasty after thrombolysis is now recommended for ST-elevation myocardial infarction, but the current guidelines propose a wide time-window ranging between 3 and 24h after lytic administration. To identify the optimal timing for PCI after thrombolysis, we analyzed frequency and time course of the adverse events in patients randomized in the multicenter CARESS-in-AMI trial. METHODS: 598 high-risk patients with STEMI recruited in the CARESS-in-AMI study, were divided into the Immediate PCI group (IMM, n=298), Rescue PCI group (RES, n=107) and Standard Treatment Arm without rescue PCI (STA, n=193). RESULTS: RES patients had worse pre-procedural TIMI flow and post-procedural blush grade. At 30 days, there were 23 deaths: 11 (10.3%) in RES, 9 (3%) in IMM and 3 (1.6%) in STA (p<0.001). There were 22 episodes of refractory ischemia or re-infarction: 17 (8.8%) in the STA group, 4 (1.6%) in IMM and 1 (0.9%) in RES (p<0.001). In the RES group 10/11 (90.9%) deaths occurred before day 5. In the STA group, all deaths and the majority of ischemic events occurred after day 3. A reduction of risk of death was observed if PCI after thrombolysis was performed within 3.35 h from initial hospitalization. CONCLUSIONS: The mortality benefit of immediate referral to PCI after pharmacological treatment for STEMI derives from a reduction in the time to reperfusion of patients with failed thrombolysis in need of rescue PCI. In patients with evidence of successful reperfusion, "elective" PCI within 3 days may be sufficient to reduce the recurrent ischemic events.

Early aggressive versus initially conservative treatment in elderly patients with non-ST-segment elevation acute coronary syndrome: a randomized controlled trial.

OBJECTIVES: This study sought to determine the risk versus benefit ratio of an early aggressive (EA) approach in elderly patients with non-ST-segment elevation acute coronary syndromes (NSTEACS). BACKGROUND: Elderly patients have been scarcely represented in trials comparing treatment strategies in NSTEACS. METHODS: A total of 313 patients ≥ 75 years of age (mean 82 years) with NSTEACS within 48 h from qualifying symptoms were randomly allocated to an EA strategy (coronary angiography and, when indicated, revascularization within 72 h) or an initially conservative (IC) strategy (angiography and revascularization only for recurrent ischemia). The primary endpoint was the composite of death, myocardial infarction, disabling stroke, and repeat hospital stay for cardiovascular causes or severe bleeding within 1 year. RESULTS: During admission, 88% of the patients in the EA group underwent angiography (55% revascularization), compared with 29% (23% revascularization) in the IC group. The primary outcome occurred in 43 patients (27.9%) in the EA group and 55 (34.6%) in the IC group (hazard ratio [HR]: 0.80; 95% confidence interval [CI]: 0.53 to 1.19; p = 0.26). The rates of mortality (HR: 0.87; 95% CI: 0.49 to 1.56), myocardial infarction (HR: 0.67; 95% CI: 0.33 to 1.36), and repeat hospital stay (HR: 0.81; 95% CI: 0.45 to 1.46) did not differ between groups. The primary endpoint was significantly reduced in patients with elevated troponin on admission (HR: 0.43; 95% CI: 0.23 to 0.80), but not in those with normal troponin (HR: 1.67; 95% CI: 0.75 to 3.70; p for interaction = 0.03). CONCLUSIONS: The present study does not allow a definite conclusion about the benefit of an EA approach when applied systematically among elderly patients with NSTEACS. The finding of a significant interaction for the treatment effect according to troponin status at baseline should be confirmed in a larger size trial. (Italian Elderly ACS Study; NCT00510185).