557221 research-article2014
ACC0010.1177/2048872614557221European Heart Journal: Acute Cardiovascular CareMorici et al.
EUROPEAN SOCIETY OF CARDIOLOGY ®
Original scientific paper
Renal dysfunction, coronary revascularization and mortality among elderly patients with non ST elevation acute coronary syndrome
European Heart Journal: Acute Cardiovascular Care 2015, Vol. 4(5) 453–460 © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2048872614557221 acc.sagepub.com
Nuccia Morici1, Stefano De Servi2, Anna Toso3, Ernesto Murena4, Federico Piscione5, Leonardo Bolognese6, Anna Sonia Petronio7, Roberto Antonicelli8, Claudio Cavallini9, Fabio Angeli9 and Stefano Savonitto10
Abstract 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 (1year 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. Keywords acute myocardial infarction, percutaneous coronary intervention, renal disease, chronic Date received: 14 June 2014; accepted: 7 October 2014
Introduction Chronic kidney dysfunction (CKD) is quite common in patients hospitalized for acute coronary syndrome (ACS), affecting up to 43% of patients presenting with non-ST segment elevation myocardial infarction.1 The prevalence of CKD does dramatically increase with age (from 4% at age 20-39 to 47% at age >70 years),2 and portends an increased rate of adverse in-hospital and follow-up events, such as heart failure and ventricular arrhythmias,3,4 with cardiovascular disease remaining the leading cause of morbidity and mortality in this setting.1 Patients with CKD usually are excluded from clinical trials that examine therapies for coronary artery disease. This is mostly true in elderly patients, based on clinicians’ fear of higher complication rates and
1Azienda Ospedaliera Ospedale Niguarda Cà Granda, Italy 2IRCCS Policlinico S. Matteo, Italy 3Ospedale Misericordia e Dolce, Italy 4Ospedale S Maria delle Grazie, Italy 5Università di Salerno, Italy 6Ospedale San Donato, Italy 7Azienda Ospedaliera Universitaria Pisana, Italy 8INRCA, Italy 9Azienda Ospedaliera Ospedale Santa Maria della Misericordia, Italy 10Azienda Ospedaliera della Provincia di Lecco, Ospedale A. Manzoni, Italy. Corresponding author: Nuccia Morici, Cardiologia 1-Emodinamica, Azienda Ospedaliera Ospedale Niguarda Ca’ Granda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. Email: [email protected]
Downloaded from acc.sagepub.com at UNIV CALIFORNIA SANTA BARBARA on October 6, 2015
454
European Heart Journal: Acute Cardiovascular Care 4(5)
less durable results. A few studies performed in the last decades have shown that patients >75 years of age benefit from aggressive revascularization strategies both in terms of long-term survival and quality of life and they have a greater absolute risk reduction compared with younger patients.5–7 However, whether this also is true in elderly patients with ACS and CKD has not been investigated. The Italian Elderly ACS study (NCT 00510185, ClinicalTrials. gov) offers a unique opportunity to gain further information on these issues, as it enrolled a prospective population of patients of ≥75 years of age with NSTEACS.6,8 Therefore, the aim of the present study was to describe the prognostic implication of coronary revascularization in very elderly patients with and without CKD hospitalized for non ST-elevation ACS (NSTEACS).
Study outcome
Methods Study design, setting and population
Statistical analysis
At 21 participating hospitals, the Italian Elderly ACS study enrolled patients of age ≥75 years with NSTEACS admitted within 48 hours of the most recent ischemic symptoms and showing ischemic electrocardiographic (ECG) changes, or elevated cardiac markers, or both. Ischemic ECG changes include either transient ST-segment elevation or depression >0.5 mm, or persistent and definite T-wave inversion >1 mm, including the pseudo-normalization of a previously negative T-wave, in ≥2 contiguous leads. Details of the study design, setting and population have been published.6 In brief, the study randomized 313 patients to either an early invasive strategy, with coronary angiography and possible revascularization within 72 hours of admission, or an initially conservative strategy with angiography only in the case of recurrent ischemic symptoms. All patients were registered in the study by accessing a dedicated website. The treatment strategy was released immediately by a computer generated list. Signature of an informed consent form was a prerequisite for enrolment. Blood samples were obtained via a direct venous puncture from all patients at the time of randomization. Serum creatinine (Cr) was analyzed according to the method used in each local laboratory. To participate in the study, each center had to provide a quality assessment for accuracy of biomarker measurements and traceability of clinical laboratory measurement results. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation as: ([{140 - age in years} × body weight in kg]/ {72 × Cr in mg/dl}) × 0.85 (female gender). Considering the age of our study population, for the purposes of the present analysis, we classified the patients according to two categories: CrCl > 45 ml/min and < 45 ml/min. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by each institution’s human research committee.
The aim of the present analysis was to investigate the prognostic implication of coronary revascularization and CrCl on 1-year all-cause mortality. Additional outcomes considered were myocardial infarction, disabling stroke, non-disabling stroke, re-hospitalization for cardiovascular causes and major bleeding according to the Thrombolysis In Myocardial Infarction (TIMI) definition.
Follow-up Clinical visits following the index procedure were planned at 30 days, 6 months, and 12 months post-randomization. All the site-reported events were checked and adjudicated by an independent clinical events committee.
The baseline characteristics of the patients were summarized by the four mutually exclusive groups of CrCl and coronary revascularization using absolute numbers and percentages for categorical variables, and means and standard deviations (SD) or median and interquartile range (IQR) for continuous data. Analysis of variance was used to compare continuous variables, and the chi-square test or Fischer’s exact test was used to compare categorical variables. Survival plots and log rank tests were used to determine and compare the 1-year cumulative risk of events according to CrCl and coronary revascularization. The independent effect of coronary revascularization and CrCl on 1-year mortality was evaluated using the Cox proportional hazards model. We assessed the proportional hazards assumption by visually inspecting the log cumulative hazard plots. Proportional hazards were assumed. Modeladjusted hazard ratios were derived along with 95% confidence intervals (CIs). Patient characteristics considered prognostically important based on the available literature, and all covariates identified at the univariate analyses as being associated to follow-up death, were entered into the models. Variables for inclusion were carefully chosen, given the number of follow-up events, to ensure parsimony of the final models. The risk of multicollinearity was tested and excluded. Any p values
ACC0010.1177/2048872614557221European Heart Journal: Acute Cardiovascular CareMorici et al.
EUROPEAN SOCIETY OF CARDIOLOGY ®
Original scientific paper
Renal dysfunction, coronary revascularization and mortality among elderly patients with non ST elevation acute coronary syndrome
European Heart Journal: Acute Cardiovascular Care 2015, Vol. 4(5) 453–460 © The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2048872614557221 acc.sagepub.com
Nuccia Morici1, Stefano De Servi2, Anna Toso3, Ernesto Murena4, Federico Piscione5, Leonardo Bolognese6, Anna Sonia Petronio7, Roberto Antonicelli8, Claudio Cavallini9, Fabio Angeli9 and Stefano Savonitto10
Abstract 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 (1year 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. Keywords acute myocardial infarction, percutaneous coronary intervention, renal disease, chronic Date received: 14 June 2014; accepted: 7 October 2014
Introduction Chronic kidney dysfunction (CKD) is quite common in patients hospitalized for acute coronary syndrome (ACS), affecting up to 43% of patients presenting with non-ST segment elevation myocardial infarction.1 The prevalence of CKD does dramatically increase with age (from 4% at age 20-39 to 47% at age >70 years),2 and portends an increased rate of adverse in-hospital and follow-up events, such as heart failure and ventricular arrhythmias,3,4 with cardiovascular disease remaining the leading cause of morbidity and mortality in this setting.1 Patients with CKD usually are excluded from clinical trials that examine therapies for coronary artery disease. This is mostly true in elderly patients, based on clinicians’ fear of higher complication rates and
1Azienda Ospedaliera Ospedale Niguarda Cà Granda, Italy 2IRCCS Policlinico S. Matteo, Italy 3Ospedale Misericordia e Dolce, Italy 4Ospedale S Maria delle Grazie, Italy 5Università di Salerno, Italy 6Ospedale San Donato, Italy 7Azienda Ospedaliera Universitaria Pisana, Italy 8INRCA, Italy 9Azienda Ospedaliera Ospedale Santa Maria della Misericordia, Italy 10Azienda Ospedaliera della Provincia di Lecco, Ospedale A. Manzoni, Italy. Corresponding author: Nuccia Morici, Cardiologia 1-Emodinamica, Azienda Ospedaliera Ospedale Niguarda Ca’ Granda, Piazza Ospedale Maggiore 3, 20162 Milan, Italy. Email: [email protected]
Downloaded from acc.sagepub.com at UNIV CALIFORNIA SANTA BARBARA on October 6, 2015
454
European Heart Journal: Acute Cardiovascular Care 4(5)
less durable results. A few studies performed in the last decades have shown that patients >75 years of age benefit from aggressive revascularization strategies both in terms of long-term survival and quality of life and they have a greater absolute risk reduction compared with younger patients.5–7 However, whether this also is true in elderly patients with ACS and CKD has not been investigated. The Italian Elderly ACS study (NCT 00510185, ClinicalTrials. gov) offers a unique opportunity to gain further information on these issues, as it enrolled a prospective population of patients of ≥75 years of age with NSTEACS.6,8 Therefore, the aim of the present study was to describe the prognostic implication of coronary revascularization in very elderly patients with and without CKD hospitalized for non ST-elevation ACS (NSTEACS).
Study outcome
Methods Study design, setting and population
Statistical analysis
At 21 participating hospitals, the Italian Elderly ACS study enrolled patients of age ≥75 years with NSTEACS admitted within 48 hours of the most recent ischemic symptoms and showing ischemic electrocardiographic (ECG) changes, or elevated cardiac markers, or both. Ischemic ECG changes include either transient ST-segment elevation or depression >0.5 mm, or persistent and definite T-wave inversion >1 mm, including the pseudo-normalization of a previously negative T-wave, in ≥2 contiguous leads. Details of the study design, setting and population have been published.6 In brief, the study randomized 313 patients to either an early invasive strategy, with coronary angiography and possible revascularization within 72 hours of admission, or an initially conservative strategy with angiography only in the case of recurrent ischemic symptoms. All patients were registered in the study by accessing a dedicated website. The treatment strategy was released immediately by a computer generated list. Signature of an informed consent form was a prerequisite for enrolment. Blood samples were obtained via a direct venous puncture from all patients at the time of randomization. Serum creatinine (Cr) was analyzed according to the method used in each local laboratory. To participate in the study, each center had to provide a quality assessment for accuracy of biomarker measurements and traceability of clinical laboratory measurement results. Creatinine clearance (CrCl) was estimated using the Cockroft-Gault equation as: ([{140 - age in years} × body weight in kg]/ {72 × Cr in mg/dl}) × 0.85 (female gender). Considering the age of our study population, for the purposes of the present analysis, we classified the patients according to two categories: CrCl > 45 ml/min and < 45 ml/min. The study protocol conforms to the ethical guidelines of the 1975 Declaration of Helsinki as reflected in a priori approval by each institution’s human research committee.
The aim of the present analysis was to investigate the prognostic implication of coronary revascularization and CrCl on 1-year all-cause mortality. Additional outcomes considered were myocardial infarction, disabling stroke, non-disabling stroke, re-hospitalization for cardiovascular causes and major bleeding according to the Thrombolysis In Myocardial Infarction (TIMI) definition.
Follow-up Clinical visits following the index procedure were planned at 30 days, 6 months, and 12 months post-randomization. All the site-reported events were checked and adjudicated by an independent clinical events committee.
The baseline characteristics of the patients were summarized by the four mutually exclusive groups of CrCl and coronary revascularization using absolute numbers and percentages for categorical variables, and means and standard deviations (SD) or median and interquartile range (IQR) for continuous data. Analysis of variance was used to compare continuous variables, and the chi-square test or Fischer’s exact test was used to compare categorical variables. Survival plots and log rank tests were used to determine and compare the 1-year cumulative risk of events according to CrCl and coronary revascularization. The independent effect of coronary revascularization and CrCl on 1-year mortality was evaluated using the Cox proportional hazards model. We assessed the proportional hazards assumption by visually inspecting the log cumulative hazard plots. Proportional hazards were assumed. Modeladjusted hazard ratios were derived along with 95% confidence intervals (CIs). Patient characteristics considered prognostically important based on the available literature, and all covariates identified at the univariate analyses as being associated to follow-up death, were entered into the models. Variables for inclusion were carefully chosen, given the number of follow-up events, to ensure parsimony of the final models. The risk of multicollinearity was tested and excluded. Any p values
