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Predictors of Long Term Outcomes in 11,441 Consecutive Patients Following Percutaneous Coronary Interventions

  • Uri Landes
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Ran Kornowski
    Correspondence
    Corresponding author: Tel: +972-3-9377107; fax: +972-3-9249850.
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Abid Assali
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Hana Vaknin-Assa
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Gabriel Greenberg
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Eli I. Lev
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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  • Tamir Bental
    Affiliations
    Cardiology Department, Rabin Medical Center (Beilinson and Hasharon Hospitals), Petach-Tikva, Israel

    The “Sackler” Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel
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Published:January 16, 2015DOI:https://doi.org/10.1016/j.amjcard.2015.01.009
      Given the vicissitudes of percutaneous coronary intervention (PCI) technology, epidemiology, and mode of practice, the aim of this study was to define contemporary outcome predictors in a very large consecutive patient cohort. Data from 11,441 consecutive patients who underwent PCI at a tertiary medical center from April 2004 to September 2013 are presented. A comprehensive database was built using various data sources, with outcome end points defined as all-cause mortality and as a composite of death or nonfatal myocardial infarction during follow-up. Candidate variables to influence outcome were chosen a priori and were tested using multivariate time-dependent models to estimate each interaction. Mean follow-up was 5.5 years (range 3 months to 9.5 years). The cohort consisted of 75% men, 42% patients with diabetes, and 61% patients who underwent PCI in acute coronary syndrome settings and 7.8% for ST-elevation myocardial infarction. Drug-eluting stents were used in 43.4% of patients, bare-metal stents in 52%, and balloon angioplasty alone in 4.6%. In multivariate analysis, in addition to already well-recognized predictors of death or myocardial infarction such as advanced age (hazard ratio [HR] 1.031, p <0.001), female gender (HR 1.23, p <0.001), urgent setting (HR 1.23, p <0.001) and diabetes mellitus (HR 1.28, p <0.001), we particularly noted previous anemia (HR 1.55 p <0.001), previous chronic kidney injury (HR 1.93, p <0.001) and previous moderate to severe left ventricular dysfunction (HR 2.29, p <0.001). Drug-eluting stent placement was associated with better outcomes (HR 0.70, p <0.001). In conclusion, this analysis confirms the effect of some known predictors of PCI outcomes. However, the extent of their effect is modest, while other predictors may have a greater influence on outcomes. Risk stratification of PCI patients should take into account kidney injury, anemia, and left ventricular function. Drug-eluting stents provide sustained benefit.
      The treatment of atherosclerotic coronary artery disease with percutaneous coronary intervention (PCI) is ongoing, evolving, and improving.
      • Ahmed E.
      • Al Suwaidi J.
      • El-Menyar A.
      • AlBinali H.A.
      • Singh R.
      • Gehani A.A.
      Mortality trends in patients hospitalized with the initial acute myocardial infarction in a Middle Eastern country over 20 years.
      • Malenka D.J.
      • O’Connor G.T.
      The Northern New England Cardiovascular Disease Study Group: a regional collaborative effort for continuous quality improvement in cardiovascular disease.
      Simultaneously, higher risk, more complicated procedures are being executed, extending the boundaries of the targeted population. Because different patients may be at widely varying risks for complications, risk stratification tools are essential to help physicians and their patients make informed clinical decisions. Only by integrating modernized, established prognostic variables, given the quantified prognostic influence of each, can precise risk/benefit ratio estimation be done. Over the years, numerous risk stratification tools have been developed on the basis of some of the notorious risk factors for adverse outcomes of PCI: advanced age, diabetes mellitus, elevated cardiac enzymes, ST-segment deviation, high Killip class, ongoing chest pain, multivessel disease, and so on.
      • Antman E.M.
      • Cohen M.
      • Bernink P.
      • McCabe C.H.
      • Horacek T.
      • Papuchis G.
      • Mautner B.
      • Corbalan R.
      • Radley D.
      • Braunwald E.
      The TIMI risk score for unstable angina∖non-ST elevation MI.
      • Fox K.A.
      • Dabbous O.H.
      • Goldberg R.J.
      • Pieper K.S.
      • Eagle K.A.
      • Van de Werf F.
      • Avezum A.
      • Goodman S.G.
      • Flather M.D.
      • Anderson Jr., F.A.
      • Granger C.B.
      Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
      • Kimmel S.E.
      • Berlin J.A.
      • Strom B.L.
      • Laskey W.K.
      Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.
      • Lee C.H.
      • van Domburg R.T.
      • Hoye A.
      • Lemos P.A.
      • Tanabe K.
      • Smits P.C.
      • van der Giessen W.J.
      • de Feyter P.
      • Serruys P.W.
      Predictors of survival after contemporary percutaneous coronary revascularization for acute myocardial infarction in the real world.
      • O’Connor G.T.
      • Malenka D.J.
      • Quinton H.
      • Robb J.F.
      • Kellett Jr., M.A.
      • Shubrooks S.
      • Bradley W.A.
      • Hearne M.J.
      • Watkins M.W.
      • Wennberg D.E.
      • Hettleman B.
      • O’Rourke D.J.
      • McGrath P.D.
      • VerLee P.
      Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994–1996. Northern New England Cardiovascular Disease Study Group.
      • Resnic F.S.
      • Ohno-Machado L.
      • Selwyn A.
      • Simon D.I.
      • Popma J.J.
      Simplified risk score models accurately predict the risk of major in-hospital complications following percutaneous coronary intervention.
      It is unclear whether these characteristics still dictate the prognosis in the contemporary PCI era using novel stents, techniques, and adjunctive pharmacotherapy. Over the past few years, we have managed a comprehensive database including all patients who undergo PCI at our 2 hospitals’ medical centers. We sought to define the matter of prognostic outcomes and outcome predictors in this very large, updated, consecutive patient cohort.

      Methods

      The study population comprised all consecutive patients (n = 11,441) who underwent PCI at our institution at the 2 hospitals of the Rabin Medical Center in Israel from April 2004 to September 2013. Data collection was approved by the hospital ethics committee in compliance with the Declaration of Helsinki. As we have previously reported,
      • Kornowski R.
      • Vaknin-Assa H.
      • Assali A.
      • Lev E.I.
      • Porter A.
      • Battler A.
      • Bental T.
      A comparative analysis of major clinical outcomes with drug-eluting stents versus bare metal stents in male versus female patients.
      • Bental T.
      • Assali A.
      • Vaknin-Assa H.
      • Lev E.I.
      • Brosh D.
      • Fuchs S.
      • Battler A.
      • Kornowski R.
      Comparative analysis of major clinical outcomes using drug-eluting stents versus bare-metal stents in a large consecutive patient cohort.
      • Codner P.
      • Bental T.
      • Assali A.
      • Vaknin-Assa H.
      • Lev E.
      • Kornowski R.
      Long-term comparative analysis from an all-comer cohort of coronary patients treated using first- and second-generation drug-eluting stents.
      • Assali A.
      • Vaduganathan M.
      • Vaknin-Assa H.
      • Lev E.I.
      • Brosh D.
      • Teplitsky I.
      • Bental T.
      • Battler A.
      • Kornowski R.
      Comparison of late (3-year) registry data outcomes using bare metal versus drug-eluting stents for treating ST-segment elevation acute myocardial infarctions.
      all data regarding the index and subsequent procedures, as well as clinical and echocardiographic data, were extracted from the patients’ electronic medical records. Demographic data and death dates were obtained from the medical centers’ demographic information system, which is linked to the State of Israel Ministry of Interior data system and the Clalit Health Organization data warehouse. The accuracy of the mortality data were verified with the Israel Central Bureau of Statistics. All data regarding previous and subsequent hospitalizations, including all International Classification of Diseases, Ninth Revision, diagnoses, were retrieved from the medical centers’ data warehouse. Laboratory data were retrieved from the medical centers’ central laboratory database. Definitions regarding ST-elevation myocardial infarction (STEMI) were obtained from the Rabin Medical Center interventional cardiology database, which records detailed data regarding all patients with STEMIs. All follow-up data were collected up to September 30, 2013.
      An initial list of candidate variables to influence outcome was chosen a priori, selected and based on relevance, as identified in previous research, or by the researchers’ clinical experience. Baseline demographic, clinical and angiographic parameters were then examined by univariate logistic regression analysis for their relation to the study outcome of interest: death or myocardial infarction (MI) during follow-up.
      On the basis of previous studies, the left ventricular ejection fraction, creatinine clearance (CrCl), and hemoglobin level were all dichotomized and treated as binary variables.
      • Antman E.M.
      • Cohen M.
      • Bernink P.
      • McCabe C.H.
      • Horacek T.
      • Papuchis G.
      • Mautner B.
      • Corbalan R.
      • Radley D.
      • Braunwald E.
      The TIMI risk score for unstable angina∖non-ST elevation MI.
      • Zaret B.L.
      • Wackers F.J.
      • Terrin M.L.
      • Forman S.A.
      • Williams D.O.
      • Knatterud G.L.
      • Braunwald E.
      Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis In Myocardial Infarction (TIMI) phase II study. The TIMI Study Group.
      • Nikolsky E.
      • Aymong E.D.
      • Halkin A.
      • Grines C.L.
      • Cox D.A.
      • Garcia E.
      • Mehran R.
      • Tcheng J.E.
      • Griffin J.J.
      • Guagliumi G.
      • Stuckey T.
      • Turco M.
      • Cohen D.A.
      • Negoita M.
      • Lansky A.J.
      • Stone G.W.
      Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.
      All patients with moderate or worse left ventricular dysfunction (LVD) defined in the echocardiographic record were flagged as “moderate to severe LVD.” All PCIs for acute/recent MI or acute coronary syndromes, defined according to the indication as noted on the electronic record, were flagged as “urgent PCI.” Primary PCI for STEMI was defined by the prerequisites for inclusion in the STEMI registry: within 12 hours of symptoms, without previous thrombolysis. All patients who arrived at the PCI laboratory after resuscitation or with cardiogenic shock were flagged as “critical state.” Chronic kidney injury (CKI), based on the Kidney Disease Outcomes Quality Initiative criteria,
      National Kidney Foundation
      K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
      was defined as estimated CrCl ≤60 ml/min (calculated using the Modification of Diet in Renal Disease [MDRD] equation). Anemia, based on World Health Organization criteria, was defined as baseline hemoglobin concentration <13 g/dl in men and <12 g/dl in women.
      • Beutler E.
      • Waalen J.
      The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?.
      To assess coronary artery disease complexity, the number of vessels with coronary disease was determined by analyzing the diagnostic catheterization report. Significant disease was considered when >50% stenosis was noted. Treated territories were defined by analyzing the angioplasty report. For each territory, PCI sites were counted (e.g., proximal and mid left anterior descending coronary artery, first or second diagonal branch) and a simple score of sites and territories, termed “complexity,” was defined, which reflects the number of discrete lesions treated per territory. Whenever treatment involved ≥1 ostial or proximal main vessel (left anterior descending, circumflex, or right coronary artery) or the left main coronary artery, the procedure was flagged as “proximal main vessel.” Total stent length was calculated and filed for each procedure. All patients with any drug-eluting stent (DES) implanted in the index PCI were included in the DES group regardless of use of any additional bare-metal stent.
      Univariate analysis was used to identify which of the candidate variables had a statistical association with the composite end point of death or MI during follow-up and with all-cause mortality (e.g., p <0.05). On the basis of this univariate analysis, we selected the most clinically meaningful variables as potential candidates for inclusion in the multivariate analysis. Multivariate logistic regression was then performed to identify independent predictors of outcomes and calculate their individual hazard ratios (i.e., effect sizes). Baseline parameters were compared between groups using Student's t test for continuous variables and the chi-square test for categorical variables. Statistical analyses were performed using IBM SPSS version 20 (IBM, Armonk, New York). All tests were 2 tailed, and p values <0.05 were considered significant. All data processing and statistical analyses were performed by the main investigator.

      Results

      Patients’ demographic, clinical, and angiographic features at the index PCI are listed in Table 1. Echocardiographic data before the PCI date was available for 6,979 of the patients (61%). Preprocedural serum creatinine and hemoglobin levels were not available for 2,288 of the patients (20%). For all other variables, <4% of values were missing. Mean follow-up time was 5.5 years (range 3 months to 9.5 years), during which a total of 1,846 deaths (16%) and 450 MIs (3.9%) occurred.
      Table 1Patient’s demographic, clinical and angiographic features at index percutaneous coronary intervention
      Cohort characteristicsNum.
      Age (years) (SD)68 (±12)
      Women2,861 (25%)
      Diabetes Mellitus4,877 (43%)
      Hypertension8,468 (74%)
      Cigarette smoker
      Current or past.
      4,002 (35%)
      Prior congestive heart failure863 (8%)
      Prior coronary bypass1676 (15%)
      Dementia167 (1%)
      Malignancy923 (8%)
      Hemoglobin [gr/dL] (SD)13.3 (±2.1)
      Prior anemia
      Hemoglobin concentration [gr/dL] <13g/dL in males and <12g/dL in females.
      5,834 (51)
      Creatinine [mg/dL] (SD)1.07 (±0.4)
      Prior chronic kidney injury
      Chronic kidney injury: CrCl ≤60 mL/min.
      2,174 (19%)
      Moderate to severe left ventricular dysfunction
      Left ventricular dysfunction defined in echocardiography.
      1,437 (13%)
      Congestive Heart failure2,345 (20.5%)
      Urgent percutaneous coronary intervention
      Proximal main vessel: left anterior descending, circumflex or right coronary artery (left main artery not included).
      6,993 (61%)
      Primary percutaneous coronary intervention892 (8%)
      Number of coronary artery narrowed
       12,588 (23%)
       23,522 (31%)
       35,188 (46%)
      Proximal main vessel
      Urgent: percutaneous coronary intervention for acute/recent MI or acute coronary syndrome.
      5,025 (44%)
      Proximal left-anterior-descending artery disease2,208 (19%)
      Mean complexity (SD)1.34 (±0.57)
      Balloon angioplasty alone526 (4.5%)
      Bare Metal Stents5,949 (52%)
      Drug eluting stents4,962 (43.5%)
      Current or past.
      Hemoglobin concentration [gr/dL] <13g/dL in males and <12g/dL in females.
      Chronic kidney injury: CrCl ≤60 mL/min.
      § Left ventricular dysfunction defined in echocardiography.
      Urgent: percutaneous coronary intervention for acute/recent MI or acute coronary syndrome.
      Proximal main vessel: left anterior descending, circumflex or right coronary artery (left main artery not included).
      Statistically significant univariate outcome predictors are listed in Table 2. In the multivariate analysis (Tables 3 and 4), in addition to well-known predictors of death or nonfatal MI such as age (adjusted hazard ratio [HR] 1.031 for death or MI and for all-cause mortality, p <0.001), female gender (HR 1.23 for death or MI and for all-cause mortality, p <0.001), diabetes mellitus (HR 1.28 for death or MI, HR 1.26 for all-cause mortality, p <0.001) and an urgent setting (HR 1.23 for death or MI, p <0.001; HR 1.09 for all-cause mortality, p = 0.115), we particularly noted previous anemia (HR 1.55 for death or MI, HR 1.75 for all-cause mortality, p <0.001), previous CKI (HR 1.93 for death or MI, HR 2.13 for all-cause mortality, p <0.001), and previous moderate to severe LVD (HR 2.29 for death or MI, HR 2.50 for all-cause mortality, p <0.001) as independent predictors. With the exception of urgent PCI and DES refraining, all outcome predictors were found to anticipate death better than the composite outcome of death and MI. Urgent PCI did not significantly predict future death risk (p = 0.115). Previous coronary artery bypass surgery and coronary artery disease complexity were not associated with higher risk. The use of a DES provided significantly better long-term outcomes (HR 0.70 for death or MI, HR 0.71 for all-cause mortality, p <0.001).
      Table 2Univariable analysis - association with Death or Myocardial infarction during follow-up
      VariableHazard-ratio95% CIp Value
      Age years1.051.05-1.06<0.001
      Women1.441.31-1.58<0.001
      Diabetes-mellitus1.641.51-1.79<0.001
      Hypertension2.041.82 -2.31<0.001
      Cigarette smoking
      Current or past. Proximal main vessel: left anterior descending, circumflex or right coronary artery (left main artery not included).
      1.451.32-1.59<0.001
      Moderate-severe left ventricular dysfunction3.092.80-3.40<0.001
      Prior coronary artery bypass surgery1.761.59 -1.95<0.001
      Proximal main vessel
      Main vessel: left anterior descending, circumflex or right coronary artery (left main artery not included).
      1.271.17 -1.39<0.001
      Proximal left-anterior-descending1.131.02 -1.26.021
      Coronary artery disease complexity1.010.94-1.090.726
      Urgent percutaneous coronary intervention
      Urgent: coronary intervention for acute or recent coronary syndrome.
      1.161.06- 1.270.001
      ST-elevation myocardial infarction1.010.87-1.170.906
      Chronic kidney injury
      Chronic kidney injury: CrCl ≤60 mL/min.
      3.202.94-3.49<0.001
      Anemia
      Anemia: hemoglobin <13g/dL in males and <12g/dL in females.
      2.202.01-2.41<0.001
      Drug eluting stent0.630.57-0.69<0.001
      Current or past. Proximal main vessel: left anterior descending, circumflex or right coronary artery (left main artery not included).
      Urgent: coronary intervention for acute or recent coronary syndrome.
      Chronic kidney injury: CrCl ≤60 mL/min.
      § Anemia: hemoglobin <13g/dL in males and <12g/dL in females.
      Main vessel: left anterior descending, circumflex or right coronary artery (left main artery not included).
      Table 3Variables associated with Death or Myocardial Infarction in the multivariable analysis
      VariableHazard-ratio95% CIp Value
      Age years1.031.03-1.04<0.001
      Women1.231.09-1.34<0.001
      Urgent percutaneous coronary intervention
      Urgent: coronary intervention for acute or recent coronary syndrome.
      1.231.08-1.31<0.001
      Diabetes-mellitus1.281.17-1.41<0.001
      Anemia
      Anemia: hemoglobin <13g/dL in males and <12g/dL in females.
      1.551.39-1.71<0.001
      Chronic kidney injury
      Chronic kidney injury: CrCl ≤60 mL/min.
      1.931.78-2.16<0.001
      Moderate-severe left ventricular dysfunction2.292.13-2.58<0.001
      Bare metal stent1.431.32-1.55<0.001
      Urgent: coronary intervention for acute or recent coronary syndrome.
      Anemia: hemoglobin <13g/dL in males and <12g/dL in females.
      Chronic kidney injury: CrCl ≤60 mL/min.
      Table 4Variables associated with Death in the multivariable analysis
      VariableHazard-ratio95% CIp Value
      Age years1.031.03-1.04<0.001
      Women1.231.10-1.37<0.001
      Urgent percutaneous coronary intervention
      Urgent: PCI for acute/recent coronary syndrome.
      1.090.98-1.210.115
      Diabetes-mellitus1.261.14-1.39<0.001
      Anemia
      Anemia: hemoglobin <13g/dL in males and <12g/dL in females.
      1.751.57-1.96<0.001
      Chronic kidney injury
      Chronic kidney injury: CrCl ≤60 mL/min.
      2.131.93-2.37<0.001
      Moderate-severe left ventricular dysfunction2.502.24-2.78<0.001
      Bare metal stent1.401.26-1.55<0.001
      Urgent: PCI for acute/recent coronary syndrome.
      Anemia: hemoglobin <13g/dL in males and <12g/dL in females.
      Chronic kidney injury: CrCl ≤60 mL/min.

      Discussion

      Numerous traditional risk factors in PCI patients were recognized using data that predate the generalized use of stents and contemporary adjuvant antithrombotic therapy. These measures might have changed not only the PCI landscape but also the epidemiology and natural history of coronary patients. Evidently, in recent years, there has been an overall mortality decrease in PCI patients,
      • Go A.S.
      • Mozaffarian D.
      • Roger V.L.
      • Benjamin E.J.
      • Berry J.D.
      • Borden W.B.
      • Bravata D.M.
      • Dai S.
      • Ford E.S.
      • Fox C.S.
      • Franco S.
      • Fullerton H.J.
      • Gillespie C.
      • Hailpern S.M.
      • Heit J.A.
      • Howard V.J.
      • Huffman M.D.
      • Kissela B.M.
      • Kittner S.J.
      • Lackland D.T.
      • Lichtman J.H.
      • Lisabeth L.D.
      • Magid D.
      • Marcus G.M.
      • Marelli A.
      • Matchar D.B.
      • McGuire D.K.
      • Mohler E.R.
      • Moy C.S.
      • Mussolino M.E.
      • Nichol G.
      • Paynter N.P.
      • Schreiner P.J.
      • Sorlie P.D.
      • Stein J.
      • Turan T.N.
      • Virani S.
      • Wong N.D.
      • Woo D.
      • Turner M.B.
      American Heart Association Statistics Committee and Stroke Statistics Subcommittee
      Executive summary: heart disease and stroke statistics—2013 update: a report from the American Heart Association.
      • Spoon D.B.
      • Psaltis P.J.
      • Singh M.
      • Holmes D.R.
      • Gersh B.K.
      • Rihal C.S.
      • Lennon R.J.
      • Moussa I.D.
      • Simari R.D.
      • Gulati R.
      Trends in cause of death after percutaneous coronary intervention.
      accompanied by a temporal switch from predominantly cardiac to predominantly noncardiac causes of death.
      • Ford E.S.
      • Ajani U.A.
      • Croft J.B.
      • Critchley J.A.
      • Labarthe D.R.
      • Kottke T.E.
      • Giles W.H.
      • Capewell S.
      Explaining the decrease in U.S. deaths from coronary disease, 1980-2000.
      Using data on 11,441 consecutive patients, we identified features associated with long-term PCI adverse outcomes. Most of the outcome predictors identified herein have been previously described,
      • Antman E.M.
      • Cohen M.
      • Bernink P.
      • McCabe C.H.
      • Horacek T.
      • Papuchis G.
      • Mautner B.
      • Corbalan R.
      • Radley D.
      • Braunwald E.
      The TIMI risk score for unstable angina∖non-ST elevation MI.
      • Fox K.A.
      • Dabbous O.H.
      • Goldberg R.J.
      • Pieper K.S.
      • Eagle K.A.
      • Van de Werf F.
      • Avezum A.
      • Goodman S.G.
      • Flather M.D.
      • Anderson Jr., F.A.
      • Granger C.B.
      Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
      • Kimmel S.E.
      • Berlin J.A.
      • Strom B.L.
      • Laskey W.K.
      Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.
      • Lee C.H.
      • van Domburg R.T.
      • Hoye A.
      • Lemos P.A.
      • Tanabe K.
      • Smits P.C.
      • van der Giessen W.J.
      • de Feyter P.
      • Serruys P.W.
      Predictors of survival after contemporary percutaneous coronary revascularization for acute myocardial infarction in the real world.
      • O’Connor G.T.
      • Malenka D.J.
      • Quinton H.
      • Robb J.F.
      • Kellett Jr., M.A.
      • Shubrooks S.
      • Bradley W.A.
      • Hearne M.J.
      • Watkins M.W.
      • Wennberg D.E.
      • Hettleman B.
      • O’Rourke D.J.
      • McGrath P.D.
      • VerLee P.
      Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994–1996. Northern New England Cardiovascular Disease Study Group.
      • Resnic F.S.
      • Ohno-Machado L.
      • Selwyn A.
      • Simon D.I.
      • Popma J.J.
      Simplified risk score models accurately predict the risk of major in-hospital complications following percutaneous coronary intervention.
      thus extending their applicability to current “all comers” PCI practice. Nevertheless, we particularly noticed some factors to have a greater influence that needs to be acknowledged (Figure 1).
      Figure thumbnail gr1
      Figure 1Effect size of different variables on the long-term risk for death or MI after PCI. Predictors of death or MI are presented on the horizontal (x) axis, each with its quantified effect size and prognostic influence (relative risk) presented on the vertical (y) axis: age (older, years), acute case (PCI for acute or recent MI or ACS), anemia (hemoglobin concentration <13 g/dl in men and <12 g/dl in women), glomerular filtration rate <60 ml/min, moderate to severe LVD (moderate or worse LVD), DES (any DES implanted in the index PCI).
      Half of the study patients (54% of the men, 48% of the women) had anemia before the index PCI. This incidence is higher than the 11% to 30% incidence reported in previous PCI study cohorts.
      • Lee C.H.
      • van Domburg R.T.
      • Hoye A.
      • Lemos P.A.
      • Tanabe K.
      • Smits P.C.
      • van der Giessen W.J.
      • de Feyter P.
      • Serruys P.W.
      Predictors of survival after contemporary percutaneous coronary revascularization for acute myocardial infarction in the real world.
      • Nikolsky E.
      • Aymong E.D.
      • Halkin A.
      • Grines C.L.
      • Cox D.A.
      • Garcia E.
      • Mehran R.
      • Tcheng J.E.
      • Griffin J.J.
      • Guagliumi G.
      • Stuckey T.
      • Turco M.
      • Cohen D.A.
      • Negoita M.
      • Lansky A.J.
      • Stone G.W.
      Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.
      This incline may well represent one of the epidemiologic changes in the PCI population in recent years and could have several explanations. Notably, one explanation could be the older mean patient age in our cohort (68 ± 12.1 years) as opposed to earlier, comprehensive, “all comers” PCI studies (i.e., 61.8 ± 11.5 years in 1993 and 66.9 ± 12.1 years in 2005).
      • Kimmel S.E.
      • Berlin J.A.
      • Strom B.L.
      • Laskey W.K.
      Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.
      After the age of 50 years, anemia prevalence rates increase rapidly.
      • Beghé C.
      • Wilson A.
      • Ershler W.B.
      Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature.
      Reasons include iron, folate, and vitamin B12 deficiencies, kidney injury, chronic inflammation, bleeding episodes, and unexplained anemia.
      • Beghé C.
      • Wilson A.
      • Ershler W.B.
      Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature.
      In our study, patients with anemia were older, had lower CrCl, and constituted a higher prevalence of moderate to severe LVD and a lower prevalence of ACS and STEMI patients. Nevertheless, after multivariate adjustments, anemia remained a powerful predictor of long-term risk for death or nonfatal MI (HR 1.55, 95% confidence interval 1.39 to 1.71) and a powerful predictor of all-cause mortality (HR 1.75, 95% confidence interval 1.57 to 1.96). When patients were further classified using an anemia severity scale (severe anemia defined as hemoglobin <11 g/dl in men and <10 g/dl in women), a dose-response type of deleterious effect was observed (HRs 4.1 for severe anemia and 1.78 for mild anemia, p <0.001). Even mild anemia, a common and often overlooked ailment, was found to be a strong mortality predictor. As such a common and potentially preventable or modifiable risk factor, a routine periprocedural screening for specific cause (e.g. iron, vitamin B12, or folate deficiency) may be cost effective and is a conceivable subject for further investigation.
      Numerous published reports have identified CKI as a strong predictor of adverse events after PCI.
      • Fox K.A.
      • Dabbous O.H.
      • Goldberg R.J.
      • Pieper K.S.
      • Eagle K.A.
      • Van de Werf F.
      • Avezum A.
      • Goodman S.G.
      • Flather M.D.
      • Anderson Jr., F.A.
      • Granger C.B.
      Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
      • Kimmel S.E.
      • Berlin J.A.
      • Strom B.L.
      • Laskey W.K.
      Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.
      • Lee C.H.
      • van Domburg R.T.
      • Hoye A.
      • Lemos P.A.
      • Tanabe K.
      • Smits P.C.
      • van der Giessen W.J.
      • de Feyter P.
      • Serruys P.W.
      Predictors of survival after contemporary percutaneous coronary revascularization for acute myocardial infarction in the real world.
      • O’Connor G.T.
      • Malenka D.J.
      • Quinton H.
      • Robb J.F.
      • Kellett Jr., M.A.
      • Shubrooks S.
      • Bradley W.A.
      • Hearne M.J.
      • Watkins M.W.
      • Wennberg D.E.
      • Hettleman B.
      • O’Rourke D.J.
      • McGrath P.D.
      • VerLee P.
      Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994–1996. Northern New England Cardiovascular Disease Study Group.
      • Resnic F.S.
      • Ohno-Machado L.
      • Selwyn A.
      • Simon D.I.
      • Popma J.J.
      Simplified risk score models accurately predict the risk of major in-hospital complications following percutaneous coronary intervention.
      • Parikh P.B.
      • Jeremias A.
      • Naidu S.S.
      • Brener S.J.
      • Lima F.
      • Shlofmitz R.A.
      • Pappas T.
      • Gruberg L.
      Impact of severity of renal dysfunction on determinants of in-hospital mortality among patients undergoing percutaneous coronary intervention.
      • Peterson E.D.
      • Dai D.
      • DeLong E.R.
      • Brennan J.M.
      • Singh M.
      • Rao S.V.
      • Shaw R.E.
      • Roe M.T.
      • Ho K.K.
      • Klein L.W.
      • Krone R.J.
      • Weintraub W.S.
      • Brindis R.G.
      • Rumsfeld J.S.
      • Spertus J.A.
      Contemporary mortality risk prediction for percutaneous coronary intervention. Results from 588,398 procedures in the national cardiovascular data registry.
      • Azar R.R.
      • Prpic R.
      • Ho K.K.
      • Kiernan F.J.
      • Shubrooks Jr., S.J.
      • Baim D.S.
      • Popma J.J.
      • Kuntz R.E.
      • Cohen D.J.
      Impact of end-stage renal disease on clinical and angiographic outcomes after coronary stenting.
      CKI may be a marker for simultaneous other typical atherosclerotic risk factors, such as hypertension, diabetes, and dyslipidemia, although it has been suggested to exert an independent effect on oxidative stress, systemic inflammation, fibrinogen, and lipid metabolism.
      • Peterson E.D.
      • Dai D.
      • DeLong E.R.
      • Brennan J.M.
      • Singh M.
      • Rao S.V.
      • Shaw R.E.
      • Roe M.T.
      • Ho K.K.
      • Klein L.W.
      • Krone R.J.
      • Weintraub W.S.
      • Brindis R.G.
      • Rumsfeld J.S.
      • Spertus J.A.
      Contemporary mortality risk prediction for percutaneous coronary intervention. Results from 588,398 procedures in the national cardiovascular data registry.
      These patients appear to have more heavily calcified, complex lesions than patients without CKI.
      • Azar R.R.
      • Prpic R.
      • Ho K.K.
      • Kiernan F.J.
      • Shubrooks Jr., S.J.
      • Baim D.S.
      • Popma J.J.
      • Kuntz R.E.
      • Cohen D.J.
      Impact of end-stage renal disease on clinical and angiographic outcomes after coronary stenting.
      In addition, patients with CKI are prone to further deterioration of their renal function after invasive cardiac procedures. In our study, CKI was found in 2,164 of the patients (18.9%) and was 1 of the strongest predictors of death or MI. Patients with CrCl ≤30 ml/min were found to have higher mortality risk (HR 4.1, p <0.001) than patients with 30 ≤CrCl ≤60 ml/min (HR 2.67, p <0.001). Similar CKI prevalence rates were reported in other observational PCI studies, with comparable adverse outcome effects.
      • Parikh P.B.
      • Jeremias A.
      • Naidu S.S.
      • Brener S.J.
      • Lima F.
      • Shlofmitz R.A.
      • Pappas T.
      • Gruberg L.
      Impact of severity of renal dysfunction on determinants of in-hospital mortality among patients undergoing percutaneous coronary intervention.
      • Peterson E.D.
      • Dai D.
      • DeLong E.R.
      • Brennan J.M.
      • Singh M.
      • Rao S.V.
      • Shaw R.E.
      • Roe M.T.
      • Ho K.K.
      • Klein L.W.
      • Krone R.J.
      • Weintraub W.S.
      • Brindis R.G.
      • Rumsfeld J.S.
      • Spertus J.A.
      Contemporary mortality risk prediction for percutaneous coronary intervention. Results from 588,398 procedures in the national cardiovascular data registry.
      • Azar R.R.
      • Prpic R.
      • Ho K.K.
      • Kiernan F.J.
      • Shubrooks Jr., S.J.
      • Baim D.S.
      • Popma J.J.
      • Kuntz R.E.
      • Cohen D.J.
      Impact of end-stage renal disease on clinical and angiographic outcomes after coronary stenting.
      PCI in patients with low left ventricular ejection fractions is known to be feasible with acceptable long-term mortality (15% 2-year mortality in a recent comprehensive PCI meta-analysis
      • Kunadian V.
      • Pugh A.
      • Zaman A.G.
      • Qiu W.
      Percutaneous coronary intervention among patients with left ventricular systolic dysfunction: a review and meta-analysis of 19 clinical studies.
      ), and LVD is not consistently incorporated in commonly used risk stratification models after PCI.
      • Antman E.M.
      • Cohen M.
      • Bernink P.
      • McCabe C.H.
      • Horacek T.
      • Papuchis G.
      • Mautner B.
      • Corbalan R.
      • Radley D.
      • Braunwald E.
      The TIMI risk score for unstable angina∖non-ST elevation MI.
      • Fox K.A.
      • Dabbous O.H.
      • Goldberg R.J.
      • Pieper K.S.
      • Eagle K.A.
      • Van de Werf F.
      • Avezum A.
      • Goodman S.G.
      • Flather M.D.
      • Anderson Jr., F.A.
      • Granger C.B.
      Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
      • Kimmel S.E.
      • Berlin J.A.
      • Strom B.L.
      • Laskey W.K.
      Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.
      • Peterson E.D.
      • Dai D.
      • DeLong E.R.
      • Brennan J.M.
      • Singh M.
      • Rao S.V.
      • Shaw R.E.
      • Roe M.T.
      • Ho K.K.
      • Klein L.W.
      • Krone R.J.
      • Weintraub W.S.
      • Brindis R.G.
      • Rumsfeld J.S.
      • Spertus J.A.
      Contemporary mortality risk prediction for percutaneous coronary intervention. Results from 588,398 procedures in the national cardiovascular data registry.
      Yet, since the plain old balloon angioplasty and bare-metal stent eras, a low ejection fraction has been associated with adverse outcomes after PCI and remains so in more recent trials.
      • De Silva K.
      • Webb I.
      • Sicard P.
      • Lockie T.
      • Pattinson S.
      • Redwood S.
      • Perera D.
      Does left ventricular function continue to influence mortality following contemporary percutaneous coronary intervention?.
      • Iqbal J.
      • Vergouwe Y.
      • Bourantas C.V.
      • Klaveren D.V.
      • Zhang Y.J.
      • Campos C.M.
      • García-García H.M.
      • Morel M.A.
      • Valgimigli M.
      • Windecker S.
      • Steyerberg E.W.
      • Serruys P.W.
      Predicting 3-year mortality after percutaneous coronary intervention. Updated logistic clinical SYNTAX score based on patient-level data from 7 contemporary stent trials.
      Notwithstanding that patients with moderate to severe LVD were older, had lower CrCl, and constituted a higher prevalence of diabetes mellitus and a lower prevalence of DES use, LVD was found to have the greatest effect on long-term prognosis (HR 2.60 for all-cause mortality, p <0.001).
      Finally, DES use was associated with long-term improved clinical outcome by an HR of 0.70 (p <0.001), as already shown in several large-scale studies.
      • Bental T.
      • Assali A.
      • Vaknin-Assa H.
      • Lev E.I.
      • Brosh D.
      • Fuchs S.
      • Battler A.
      • Kornowski R.
      Comparative analysis of major clinical outcomes using drug-eluting stents versus bare-metal stents in a large consecutive patient cohort.
      • Tu J.V.
      • Bowen J.
      • Chiu M.
      • Ko D.T.
      • Austin P.C.
      • He Y.
      • Hopkins R.
      • Tarride J.E.
      • Blackhouse G.
      • Lazzam C.
      • Cohen E.A.
      • Goeree R.
      Effectiveness and safety of drug-eluting stents in Ontario.
      • Marroquin O.C.
      • Selzer F.
      • Mulukutla S.R.
      • Williams D.O.
      • Vlachos H.A.
      • Wilensky R.L.
      • Tanguay J.F.
      • Holper E.M.
      • Abbott J.D.
      • Lee J.S.
      • Smith C.
      • Anderson W.D.
      • Kelsey S.F.
      • Kip K.E.
      A comparison of bare-metal and drug-eluting stents for off-label indications.
      The core DES effect, which has proved to be sustained over time, is reduced restenosis rate. As we have pointed out in our previous studies,
      • Bental T.
      • Assali A.
      • Vaknin-Assa H.
      • Lev E.I.
      • Brosh D.
      • Fuchs S.
      • Battler A.
      • Kornowski R.
      Comparative analysis of major clinical outcomes using drug-eluting stents versus bare-metal stents in a large consecutive patient cohort.
      • Codner P.
      • Bental T.
      • Assali A.
      • Vaknin-Assa H.
      • Lev E.
      • Kornowski R.
      Long-term comparative analysis from an all-comer cohort of coronary patients treated using first- and second-generation drug-eluting stents.
      reduced restenosis rate cannot explain the early differences in mortality rates, which may be attributed to the patterns of more complete and aggressive revascularization strategies that accompany DES use.
      • Bental T.
      • Assali A.
      • Vaknin-Assa H.
      • Lev E.I.
      • Brosh D.
      • Fuchs S.
      • Battler A.
      • Kornowski R.
      Comparative analysis of major clinical outcomes using drug-eluting stents versus bare-metal stents in a large consecutive patient cohort.
      Concerns regarding bleeding risk (due to prolonged dual antithrombotic medication intake) have recently dissipated,
      • Tamburino C.
      • Angiolillo D.J.
      • Capranzano P.
      • Dimopoulos K.
      • La Manna A.
      • Barbagallo R.
      • Tagliareni F.
      • Mangiafico S.
      • Guzman L.A.
      • Galassi A.R.
      • Bass T.A.
      Complete versus incomplete revascularization in patients with multivessel disease undergoing percutaneous coronary intervention with drug-eluting stents.
      • Kawaji T.
      • Shiomi H.
      • Morimoto T.
      • Tamura T.
      • Nishikawa R.
      • Yano M.
      • Tazaki J.
      • Imai M.
      • Saito N.
      • Makiyama T.
      • Shizuta S.
      • Ono K.
      • Kimura T.
      Long-term efficacy and safety outcomes after unrestricted use of drug-eluting stents in patients with acute coronary syndrome.
      and therefore, in addition to DESs’ favorable efficacy, might encourage further ascent in future wide-scale DES utilization.
      We report the results of a large tertiary center study, with homogeneity of policy, practice, and standards. Nevertheless, as a single-center study, results may still have restricted external validity, and further evaluation is warranted. Also, data regarding some variables were unavailable for statistical analysis and may still harbor prognostic implications (i.e., Killip class, biomarkers levels, etc.).
      This comprehensive analysis confirms the effect of notorious predictors of long-term adverse PCI outcomes, such as advanced age, diabetes mellitus, and urgent settings. However, their effect extent is modest, while supplementary predictors have a greater effect on contemporary PCI prognosis. Risk stratification of PCI patients should take account of LVD, CKI, and anemia, severe and mild. DES use may provide a sustained long-term benefit.

      Disclosures

      The authors have no conflicts of interest to disclose.

      References

        • Ahmed E.
        • Al Suwaidi J.
        • El-Menyar A.
        • AlBinali H.A.
        • Singh R.
        • Gehani A.A.
        Mortality trends in patients hospitalized with the initial acute myocardial infarction in a Middle Eastern country over 20 years.
        Cardiol Res Pract. 2014; 2014: 464323
        • Malenka D.J.
        • O’Connor G.T.
        The Northern New England Cardiovascular Disease Study Group: a regional collaborative effort for continuous quality improvement in cardiovascular disease.
        Jt Comm J Qual Improv. 1998; 10: 594-600
        • Antman E.M.
        • Cohen M.
        • Bernink P.
        • McCabe C.H.
        • Horacek T.
        • Papuchis G.
        • Mautner B.
        • Corbalan R.
        • Radley D.
        • Braunwald E.
        The TIMI risk score for unstable angina∖non-ST elevation MI.
        JAMA. 2000; 284: 835-842
        • Fox K.A.
        • Dabbous O.H.
        • Goldberg R.J.
        • Pieper K.S.
        • Eagle K.A.
        • Van de Werf F.
        • Avezum A.
        • Goodman S.G.
        • Flather M.D.
        • Anderson Jr., F.A.
        • Granger C.B.
        Prediction of risk of death and myocardial infarction in the six months after presentation with acute coronary syndrome: prospective multinational observational study (GRACE).
        BMJ. 2006; 333: 1091-1094
        • Kimmel S.E.
        • Berlin J.A.
        • Strom B.L.
        • Laskey W.K.
        Development and validation of simplified predictive index for major complications in contemporary percutaneous transluminal coronary angioplasty practice. The Registry Committee of the Society for Cardiac Angiography and Interventions.
        J Am Coll Cardiol. 1995; 26: 931-938
        • Lee C.H.
        • van Domburg R.T.
        • Hoye A.
        • Lemos P.A.
        • Tanabe K.
        • Smits P.C.
        • van der Giessen W.J.
        • de Feyter P.
        • Serruys P.W.
        Predictors of survival after contemporary percutaneous coronary revascularization for acute myocardial infarction in the real world.
        J Invasive Cardiol. 2004; 16: 627-631
        • O’Connor G.T.
        • Malenka D.J.
        • Quinton H.
        • Robb J.F.
        • Kellett Jr., M.A.
        • Shubrooks S.
        • Bradley W.A.
        • Hearne M.J.
        • Watkins M.W.
        • Wennberg D.E.
        • Hettleman B.
        • O’Rourke D.J.
        • McGrath P.D.
        • VerLee P.
        Multivariate prediction of in-hospital mortality after percutaneous coronary interventions in 1994–1996. Northern New England Cardiovascular Disease Study Group.
        J Am Coll Cardiol. 1999; 34: 681-691
        • Resnic F.S.
        • Ohno-Machado L.
        • Selwyn A.
        • Simon D.I.
        • Popma J.J.
        Simplified risk score models accurately predict the risk of major in-hospital complications following percutaneous coronary intervention.
        Am J Cardiol. 2001; 88: 5-9
        • Kornowski R.
        • Vaknin-Assa H.
        • Assali A.
        • Lev E.I.
        • Porter A.
        • Battler A.
        • Bental T.
        A comparative analysis of major clinical outcomes with drug-eluting stents versus bare metal stents in male versus female patients.
        Eurointervention. 2012; 7: 1051-1059
        • Bental T.
        • Assali A.
        • Vaknin-Assa H.
        • Lev E.I.
        • Brosh D.
        • Fuchs S.
        • Battler A.
        • Kornowski R.
        Comparative analysis of major clinical outcomes using drug-eluting stents versus bare-metal stents in a large consecutive patient cohort.
        Catheter Cardiovasc Interv. 2010; 76: 374-380
        • Codner P.
        • Bental T.
        • Assali A.
        • Vaknin-Assa H.
        • Lev E.
        • Kornowski R.
        Long-term comparative analysis from an all-comer cohort of coronary patients treated using first- and second-generation drug-eluting stents.
        J Invasive Cardiol. 2014; 26: 378-384
        • Assali A.
        • Vaduganathan M.
        • Vaknin-Assa H.
        • Lev E.I.
        • Brosh D.
        • Teplitsky I.
        • Bental T.
        • Battler A.
        • Kornowski R.
        Comparison of late (3-year) registry data outcomes using bare metal versus drug-eluting stents for treating ST-segment elevation acute myocardial infarctions.
        Am J Cardiol. 2012; 109: 1563-1568
        • Zaret B.L.
        • Wackers F.J.
        • Terrin M.L.
        • Forman S.A.
        • Williams D.O.
        • Knatterud G.L.
        • Braunwald E.
        Value of radionuclide rest and exercise left ventricular ejection fraction in assessing survival of patients after thrombolytic therapy for acute myocardial infarction: results of Thrombolysis In Myocardial Infarction (TIMI) phase II study. The TIMI Study Group.
        J Am Collcardiol. 1995; 26: 73-79
        • Nikolsky E.
        • Aymong E.D.
        • Halkin A.
        • Grines C.L.
        • Cox D.A.
        • Garcia E.
        • Mehran R.
        • Tcheng J.E.
        • Griffin J.J.
        • Guagliumi G.
        • Stuckey T.
        • Turco M.
        • Cohen D.A.
        • Negoita M.
        • Lansky A.J.
        • Stone G.W.
        Impact of anemia in patients with acute myocardial infarction undergoing primary percutaneous coronary intervention: analysis from the Controlled Abciximab and Device Investigation to Lower Late Angioplasty Complications (CADILLAC) trial.
        J Am Coll Cardiol. 2004; 44: 547-553
        • National Kidney Foundation
        K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification.
        Am J Kidney Dis. 2002; 39: S1-266
        • Beutler E.
        • Waalen J.
        The definition of anemia: what is the lower limit of normal of the blood hemoglobin concentration?.
        Blood. 2006; 107: 1747-1750
        • Go A.S.
        • Mozaffarian D.
        • Roger V.L.
        • Benjamin E.J.
        • Berry J.D.
        • Borden W.B.
        • Bravata D.M.
        • Dai S.
        • Ford E.S.
        • Fox C.S.
        • Franco S.
        • Fullerton H.J.
        • Gillespie C.
        • Hailpern S.M.
        • Heit J.A.
        • Howard V.J.
        • Huffman M.D.
        • Kissela B.M.
        • Kittner S.J.
        • Lackland D.T.
        • Lichtman J.H.
        • Lisabeth L.D.
        • Magid D.
        • Marcus G.M.
        • Marelli A.
        • Matchar D.B.
        • McGuire D.K.
        • Mohler E.R.
        • Moy C.S.
        • Mussolino M.E.
        • Nichol G.
        • Paynter N.P.
        • Schreiner P.J.
        • Sorlie P.D.
        • Stein J.
        • Turan T.N.
        • Virani S.
        • Wong N.D.
        • Woo D.
        • Turner M.B.
        • American Heart Association Statistics Committee and Stroke Statistics Subcommittee
        Executive summary: heart disease and stroke statistics—2013 update: a report from the American Heart Association.
        Circulation. 2013; 127: 143-152
        • Spoon D.B.
        • Psaltis P.J.
        • Singh M.
        • Holmes D.R.
        • Gersh B.K.
        • Rihal C.S.
        • Lennon R.J.
        • Moussa I.D.
        • Simari R.D.
        • Gulati R.
        Trends in cause of death after percutaneous coronary intervention.
        Circulation. 2014; 129: 1286-1294
        • Ford E.S.
        • Ajani U.A.
        • Croft J.B.
        • Critchley J.A.
        • Labarthe D.R.
        • Kottke T.E.
        • Giles W.H.
        • Capewell S.
        Explaining the decrease in U.S. deaths from coronary disease, 1980-2000.
        N Engl J Med. 2007; 356: 2388-2398
        • Beghé C.
        • Wilson A.
        • Ershler W.B.
        Prevalence and outcomes of anemia in geriatrics: a systematic review of the literature.
        Am J Med. 2004; 116: 3S-10S
        • Parikh P.B.
        • Jeremias A.
        • Naidu S.S.
        • Brener S.J.
        • Lima F.
        • Shlofmitz R.A.
        • Pappas T.
        • Gruberg L.
        Impact of severity of renal dysfunction on determinants of in-hospital mortality among patients undergoing percutaneous coronary intervention.
        Catheter Cardiovasc Interv. 2012; 80: 352-357
        • Peterson E.D.
        • Dai D.
        • DeLong E.R.
        • Brennan J.M.
        • Singh M.
        • Rao S.V.
        • Shaw R.E.
        • Roe M.T.
        • Ho K.K.
        • Klein L.W.
        • Krone R.J.
        • Weintraub W.S.
        • Brindis R.G.
        • Rumsfeld J.S.
        • Spertus J.A.
        Contemporary mortality risk prediction for percutaneous coronary intervention. Results from 588,398 procedures in the national cardiovascular data registry.
        J Am Coll Cardiol. 2010; 55: 1923-1932
        • Azar R.R.
        • Prpic R.
        • Ho K.K.
        • Kiernan F.J.
        • Shubrooks Jr., S.J.
        • Baim D.S.
        • Popma J.J.
        • Kuntz R.E.
        • Cohen D.J.
        Impact of end-stage renal disease on clinical and angiographic outcomes after coronary stenting.
        Am J Cardiol. 2000; 86: 485-489
        • Kunadian V.
        • Pugh A.
        • Zaman A.G.
        • Qiu W.
        Percutaneous coronary intervention among patients with left ventricular systolic dysfunction: a review and meta-analysis of 19 clinical studies.
        Coron Artery Dis. 2012; 23: 469-479
        • De Silva K.
        • Webb I.
        • Sicard P.
        • Lockie T.
        • Pattinson S.
        • Redwood S.
        • Perera D.
        Does left ventricular function continue to influence mortality following contemporary percutaneous coronary intervention?.
        Coron Artery Dis. 2012; 23: 155-161
        • Iqbal J.
        • Vergouwe Y.
        • Bourantas C.V.
        • Klaveren D.V.
        • Zhang Y.J.
        • Campos C.M.
        • García-García H.M.
        • Morel M.A.
        • Valgimigli M.
        • Windecker S.
        • Steyerberg E.W.
        • Serruys P.W.
        Predicting 3-year mortality after percutaneous coronary intervention. Updated logistic clinical SYNTAX score based on patient-level data from 7 contemporary stent trials.
        J Am Coll Cardiol. 2014; 7: 464-470
        • Tu J.V.
        • Bowen J.
        • Chiu M.
        • Ko D.T.
        • Austin P.C.
        • He Y.
        • Hopkins R.
        • Tarride J.E.
        • Blackhouse G.
        • Lazzam C.
        • Cohen E.A.
        • Goeree R.
        Effectiveness and safety of drug-eluting stents in Ontario.
        N Engl J Med. 2007; 357: 1393-1402
        • Marroquin O.C.
        • Selzer F.
        • Mulukutla S.R.
        • Williams D.O.
        • Vlachos H.A.
        • Wilensky R.L.
        • Tanguay J.F.
        • Holper E.M.
        • Abbott J.D.
        • Lee J.S.
        • Smith C.
        • Anderson W.D.
        • Kelsey S.F.
        • Kip K.E.
        A comparison of bare-metal and drug-eluting stents for off-label indications.
        N Engl J Med. 2008; 358: 342-352
        • Tamburino C.
        • Angiolillo D.J.
        • Capranzano P.
        • Dimopoulos K.
        • La Manna A.
        • Barbagallo R.
        • Tagliareni F.
        • Mangiafico S.
        • Guzman L.A.
        • Galassi A.R.
        • Bass T.A.
        Complete versus incomplete revascularization in patients with multivessel disease undergoing percutaneous coronary intervention with drug-eluting stents.
        Catheter Cardiovasc Interv. 2008; 72: 448-456
        • Kawaji T.
        • Shiomi H.
        • Morimoto T.
        • Tamura T.
        • Nishikawa R.
        • Yano M.
        • Tazaki J.
        • Imai M.
        • Saito N.
        • Makiyama T.
        • Shizuta S.
        • Ono K.
        • Kimura T.
        Long-term efficacy and safety outcomes after unrestricted use of drug-eluting stents in patients with acute coronary syndrome.
        Circ J. 2014; 78: 1628-1635