clinical trial results. org characteristics, management, and outcomes of 5,557 patients age ≥90...
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Clinical Trial Results . orgClinical Trial Results . org
Characteristics, Management, and Outcomes of 5,557 Patients Age ≥90 Years With Acute Coronary
Syndromes: Results From the CRUSADE Initiative
Characteristics, Management, and Outcomes of 5,557 Patients Age ≥90 Years With Acute Coronary
Syndromes: Results From the CRUSADE Initiative
Adam H. Skolnick, MD, Karen P. Alexander, MD, Anita Y. Chen, Adam H. Skolnick, MD, Karen P. Alexander, MD, Anita Y. Chen, MS, Matthew T. Roe, MD, MSH, Charles V. Pollack, Jr, MD, MA, E. MS, Matthew T. Roe, MD, MSH, Charles V. Pollack, Jr, MD, MA, E.
Magnus Ohman, MD, John S. Rumsfeld, MD, PhD, W. Brian Magnus Ohman, MD, John S. Rumsfeld, MD, PhD, W. Brian Gibler, MD, Eric D. Peterson, MD, MPH, David J. Cohen, MD, MScGibler, MD, Eric D. Peterson, MD, MPH, David J. Cohen, MD, MSc
J Am Coll Cardiol 2007; 49:1790-7J Am Coll Cardiol 2007; 49:1790-7
The CRUSADE National Quality Improvement InitiativeThe CRUSADE National Quality Improvement Initiative The CRUSADE National Quality Improvement InitiativeThe CRUSADE National Quality Improvement Initiative
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CRUSADE: BackgroundCRUSADE: Background
• Patients aged 90 and older (the “oldest old”) are Patients aged 90 and older (the “oldest old”) are often excluded from clinical trials and included in often excluded from clinical trials and included in low numbers in clinical registrieslow numbers in clinical registries
• In particular, little is known about contemporary In particular, little is known about contemporary treatment and outcomes of acute coronary treatment and outcomes of acute coronary syndromes in such patientssyndromes in such patients
• Patients aged 90 and older (the “oldest old”) are Patients aged 90 and older (the “oldest old”) are often excluded from clinical trials and included in often excluded from clinical trials and included in low numbers in clinical registrieslow numbers in clinical registries
• In particular, little is known about contemporary In particular, little is known about contemporary treatment and outcomes of acute coronary treatment and outcomes of acute coronary syndromes in such patientssyndromes in such patients
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: ObjectivesCRUSADE: Objectives
• Describe key differences in baseline characteristics Describe key differences in baseline characteristics and ACS presentation among patients age 90 and and ACS presentation among patients age 90 and older compared with a relatively younger cohortolder compared with a relatively younger cohort
• Determine current treatment patterns in the oldest oldDetermine current treatment patterns in the oldest old
• Determine presenting characteristics associated with Determine presenting characteristics associated with in-hospital mortality among the oldest old with ACSin-hospital mortality among the oldest old with ACS
• Describe key differences in baseline characteristics Describe key differences in baseline characteristics and ACS presentation among patients age 90 and and ACS presentation among patients age 90 and older compared with a relatively younger cohortolder compared with a relatively younger cohort
• Determine current treatment patterns in the oldest oldDetermine current treatment patterns in the oldest old
• Determine presenting characteristics associated with Determine presenting characteristics associated with in-hospital mortality among the oldest old with ACSin-hospital mortality among the oldest old with ACS
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: Study DesignCRUSADE: Study Design
Primary Endpoint: Compare baseline characteristics, treatment Primary Endpoint: Compare baseline characteristics, treatment patterns, and in-hospital outcomes of both cohortspatterns, and in-hospital outcomes of both cohorts
Primary Endpoint: Compare baseline characteristics, treatment Primary Endpoint: Compare baseline characteristics, treatment patterns, and in-hospital outcomes of both cohortspatterns, and in-hospital outcomes of both cohorts
Cohort A Cohort A Pts Pts >>90 yrs90 yrs
n=5,557n=5,557
Cohort A Cohort A Pts Pts >>90 yrs90 yrs
n=5,557n=5,557
Cohort B Cohort B Pts 75 to 89 yrsPts 75 to 89 yrs
n=46,270n=46,270
Cohort B Cohort B Pts 75 to 89 yrsPts 75 to 89 yrs
n=46,270n=46,270
51,827 patients 51,827 patients >>75 years with NSTE-ACS from CRUSADE Registry 75 years with NSTE-ACS from CRUSADE Registry arriving at a participating facility either via the emergency department or by transfer within 24 h of onset of arriving at a participating facility either via the emergency department or by transfer within 24 h of onset of
symptoms. In addition, initial evaluation must reveal 1 or more high-risk features including ST-segment symptoms. In addition, initial evaluation must reveal 1 or more high-risk features including ST-segment depression, transient ST-segment elevation, or elevated levels of biomarkersdepression, transient ST-segment elevation, or elevated levels of biomarkers
51,827 patients 51,827 patients >>75 years with NSTE-ACS from CRUSADE Registry 75 years with NSTE-ACS from CRUSADE Registry arriving at a participating facility either via the emergency department or by transfer within 24 h of onset of arriving at a participating facility either via the emergency department or by transfer within 24 h of onset of
symptoms. In addition, initial evaluation must reveal 1 or more high-risk features including ST-segment symptoms. In addition, initial evaluation must reveal 1 or more high-risk features including ST-segment depression, transient ST-segment elevation, or elevated levels of biomarkersdepression, transient ST-segment elevation, or elevated levels of biomarkers
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: Baseline CharacteristicsCRUSADE: Baseline Characteristics
CharacteristicCharacteristic 75-89 y.o.75-89 y.o.(N= 46,270)(N= 46,270)
Age Age ≥ 90≥ 90(N=5,557)(N=5,557)
p-valuep-value
Age (yrs)Age (yrs) 81.0 81.0 ± 4.0± 4.0 92.6 92.6 ± 2.6± 2.6 <0.001<0.001
Caucasian (%)Caucasian (%) 85.785.7 86.186.1 NSNS
Female (%)Female (%) 50.150.1 67.467.4 <0.001<0.001
Diabetes Mellitus (%)Diabetes Mellitus (%) 34.234.2 20.420.4 <0.001<0.001
Hypertension (%)Hypertension (%) 76.176.1 73.773.7 <0.001<0.001
Peripheral Vascular Disease (%)Peripheral Vascular Disease (%) 15.615.6 10.710.7 <0.001<0.001
Obesity (BMI>30) (%)Obesity (BMI>30) (%) 18.918.9 7.67.6 <0.001<0.001
Recent/current smoker (%)Recent/current smoker (%) 8.88.8 2.52.5 <0.001<0.001
Family History of CAD (%)Family History of CAD (%) 25.025.0 14.814.8 <0.001<0.001
Prior Aspirin use (%)Prior Aspirin use (%) 49.249.2 46.746.7 0.0010.001
Previous PCI (%)Previous PCI (%) 20.120.1 8.78.7 <0.001<0.001
History of CHF (%)History of CHF (%) 26.926.9 39.339.3 <0.001<0.001
Creatinine Clearance (ml/min)Creatinine Clearance (ml/min) 36.036.0 23.923.9 <0.001<0.001
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: Findings at AdmissionCRUSADE: Findings at Admission
FindingFinding 75-89 yrs75-89 yrs(N= 46,270)(N= 46,270)
Age Age ≥ 90≥ 90(N=5,557)(N=5,557)
p-valuep-value
ST-segment depressions (%)ST-segment depressions (%) 36.936.9 3535 <0.001<0.001
CK-MB positive (%)CK-MB positive (%) 71.171.1 74.174.1 <0.001<0.001
Troponin positive (%)Troponin positive (%) 81.881.8 86.886.8 <0.001<0.001
SBP <90 mm Hg (%)SBP <90 mm Hg (%) 4.14.1 4.94.9 0.0040.004
HR >100 bpm (%)HR >100 bpm (%) 25.525.5 28.928.9 <0.001<0.001
Signs of CHF (%)Signs of CHF (%) 33.733.7 45.445.4 <0.001<0.001
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: In-Hospital TherapiesCRUSADE: In-Hospital Therapies
TherapyTherapy 75-89 y.o.75-89 y.o.(N= 46,270)(N= 46,270)
Age Age ≥ 90≥ 90(N=5,557)(N=5,557)
p-valuep-value
Aspirin (%)Aspirin (%) 91.791.7 90.690.6 0.0110.011
Beta-blocker (%)Beta-blocker (%) 82.282.2 80.780.7 0.0170.017
Heparin, any route (%)Heparin, any route (%) 82.482.4 75.175.1 <0.001<0.001
Clopidogrel (%)Clopidogrel (%) 40.140.1 35.535.5 <0.001<0.001
Statin (%)Statin (%) 45.745.7 30.430.4 <0.001<0.001
ACE-I (%)ACE-I (%) 47.147.1 45.345.3 0.0250.025
Gp IIb/IIIa inhibitor (%)Gp IIb/IIIa inhibitor (%) 29.229.2 12.012.0 <0.001<0.001
Coronary Revasc, any (%)Coronary Revasc, any (%) 40.140.1 12.612.6 <0.001<0.001
PCI w/in 1PCI w/in 1stst 48 hours (%) 48 hours (%) 20.220.2 6.56.5 <0.001<0.001
CABG (%)CABG (%) 9.49.4 1.11.1 <0.001<0.001
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: In-hospital Adverse OutcomesCRUSADE: In-hospital Adverse Outcomes
OutcomeOutcome 75-89 y.o.75-89 y.o.(N=46,270)(N=46,270)
Age Age ≥ 90≥ 90(N=5,557)(N=5,557)
p-valuep-value
Death (%)Death (%) 7.87.8 12.012.0 <0.001<0.001
MI (%)MI (%) 3.53.5 3.03.0 NSNS
Stroke (%)Stroke (%) 1.21.2 0.90.9 0.0320.032
Cardiogenic Shock (%)Cardiogenic Shock (%) 3.53.5 3.13.1 NSNS
CHF (%)CHF (%) 12.912.9 16.416.4 <0.001<0.001
RBC Transfusion RBC Transfusion ŧŧ 14.114.1 12.812.8 --Major Bleeding Event** Major Bleeding Event** ŧŧ (%) (%) 13.113.1 9.99.9 <0.001<0.001Any Adverse Outcome Any Adverse Outcome ŁŁ(%)(%) 21.321.3 26.826.8 --
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
** Major Bleeding: (1) Hct decline >11% (2) Intracranial Hemorrhage (3) Retroperitoneal hemorrhage (4) Baseline Hct >27% w/ transfusion (5) Witnessed bleeding event w/ baseline Hct <28 w/ transfusion
ŧ Excluded patients who underwent bypass surgery
Ł Any adverse outcome: post-admission MI, cardiogenic shock, heart failure, stroke, or death
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14.7%
8.3%6.7% 6.2%
18.9%
11.0%10.2%
11.1%
0%
5%
10%
15%
20%
25%
30%
0-25% 26-50% 51-75% 76-100%
Age 75-89 Age ≥ 90
14.7%
8.3%6.7% 6.2%
18.9%
11.0%10.2%
11.1%
0%
5%
10%
15%
20%
25%
30%
0-25% 26-50% 51-75% 76-100%
Age 75-89 Age ≥ 90
CRUSADE: In-hospital Mortality Across Each Age Group With Increasing Adherence to Recommended Therapies
CRUSADE: In-hospital Mortality Across Each Age Group With Increasing Adherence to Recommended Therapies
In-H
ospi
tal M
orta
lity
(%
)In
-Hos
pita
l Mor
talit
y (
%)
Guidelines recommended therapies included acute (<24h) aspirin, acute B-blockers, acute Guidelines recommended therapies included acute (<24h) aspirin, acute B-blockers, acute heparin and cardiac catheterization within 48h, and receipt of glycoprotein IIb/IIIa inhibitors for heparin and cardiac catheterization within 48h, and receipt of glycoprotein IIb/IIIa inhibitors for patients undergoing early catheterization.patients undergoing early catheterization.
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
Percent Adherence ScorePercent Adherence Score
P-value for trend <0.001
P-value for age-treatment interaction = NS
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9.0%8.3%
11.2% 10.8%11.4%
15.4%
0.0%
3.5%
10.9% 11.3%
13.6%
17.3%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
None One Two Three Four Five
Age 75-89 Age ≥ 90
9.0%8.3%
11.2% 10.8%11.4%
15.4%
0.0%
3.5%
10.9% 11.3%
13.6%
17.3%
0%
2%
4%
6%
8%
10%
12%
14%
16%
18%
20%
None One Two Three Four Five
Age 75-89 Age ≥ 90
CRUSADE: Number of Therapies Provided and the Incidence of In-Hospital Bleeding
CRUSADE: Number of Therapies Provided and the Incidence of In-Hospital Bleeding
Maj
or B
leed
ing
(%
)M
ajor
Ble
edin
g (
%)
*Therapies: (1) Aspirin (2) Beta-blocker (3) Heparin (4) Cath w/in 48 hrs w/ *Therapies: (1) Aspirin (2) Beta-blocker (3) Heparin (4) Cath w/in 48 hrs w/ IIb/IIIa (5) Cath w/in 48 hrs. IIb/IIIa (5) Cath w/in 48 hrs. (CABG Pts and contraindications excluded)(CABG Pts and contraindications excluded)
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
Number of Therapies Received *Number of Therapies Received *
P-value for trend <0.001
P-value for age-treatment interaction = NS
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CRUSADE: Multivariate Analysis: Independent Predictors of In-hospital Mortality Among Patients Aged ≥90
CRUSADE: Multivariate Analysis: Independent Predictors of In-hospital Mortality Among Patients Aged ≥90
FindingFinding Adjusted O.R. Adjusted O.R. (95% C.I.)(95% C.I.)
p-valuep-value
Systolic BP (by 10 mm Hg)Systolic BP (by 10 mm Hg) 1.19 (1.16-1.23)1.19 (1.16-1.23) <0.001<0.001
Signs of CHFSigns of CHF 1.76 (1.45-2.15)1.76 (1.45-2.15) <0.001<0.001
Renal InsufficiencyRenal Insufficiency 1.48 (1.23-1.78)1.48 (1.23-1.78) <0.001<0.001
Troponin RatioTroponin Ratio 1.01 (1.00-1.02)1.01 (1.00-1.02) <0.001<0.001
Diabetes MellitusDiabetes Mellitus 1.38 (1.14-1.67)1.38 (1.14-1.67) <0.001<0.001
BMI >25 vs. normalBMI >25 vs. normal 1.30 (1.08-1.57)1.30 (1.08-1.57) 0.0260.026
Prior PCI Prior PCI 0.63 (0.45-0.90)0.63 (0.45-0.90) 0.0010.001
DyslipidemiaDyslipidemia 0.78 (0.65-0.95)0.78 (0.65-0.95) 0.0140.014
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: LimitationsCRUSADE: Limitations
• Further studies are necessary to validate this risk model and to better understand long-term outcomes in this challenging population
• Further studies are necessary to validate this risk model and to better understand long-term outcomes in this challenging population
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: SummaryCRUSADE: Summary
• Among the oldest old with ACS, traditional risk Among the oldest old with ACS, traditional risk factors for CAD were less common compared factors for CAD were less common compared with the patients aged 75-89, while CHF and with the patients aged 75-89, while CHF and renal dysfunction were more common.renal dysfunction were more common.
• After excluding those with contraindications, After excluding those with contraindications, use of evidence-based medications, early use of evidence-based medications, early catheterization and revascularization were less catheterization and revascularization were less common among the oldest oldcommon among the oldest old
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: SummaryCRUSADE: Summary
• Despite an association with major bleeding, Despite an association with major bleeding, increasing use of evidence-based therapies was increasing use of evidence-based therapies was associated with lower in-hospital mortality even associated with lower in-hospital mortality even among the oldest old with ACSamong the oldest old with ACS
• Among the oldest old with ACS, diabetes and Among the oldest old with ACS, diabetes and renal insufficiency were independently renal insufficiency were independently associated with increased in-hospital mortality, associated with increased in-hospital mortality, while elevated systolic BP, prior PCI and while elevated systolic BP, prior PCI and dyslipidemia were associated with decreased in-dyslipidemia were associated with decreased in-hospital mortalityhospital mortality
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007
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CRUSADE: SummaryCRUSADE: Summary
• ACS in the oldest old is associated with substantial morbidity and mortality compared with a younger elderly population
• Since adherence to ACC/AHA recommended therapies appears to be associated with improved outcomes in this group, advanced age alone should not deter efforts to optimize care for such patients
• ACS in the oldest old is associated with substantial morbidity and mortality compared with a younger elderly population
• Since adherence to ACC/AHA recommended therapies appears to be associated with improved outcomes in this group, advanced age alone should not deter efforts to optimize care for such patients
Skolnick et al., JACC Vol.49, No.17, 2007Skolnick et al., JACC Vol.49, No.17, 2007