Trend in crescita in cardiologia interventistica e non

1
Trend in crescita in cardiologia interventistica
e non
Diabete, anziani e pazienti vulnerabili. Cosa fare
Autore
Stefano Savonitto
Cariologia Invasiva. Sessione Scientifica 2007,
GISE Regione Lombardia, Stresa 30 Novembre 1
Dicembre 2007
2
www.degasperis.it
Questa presentazione sarà disponibile al più
presto sul sito della Fondazione De Gasperis
nella sezione Area Medici
3
Age gt70y, diabetes and chronic renal
dysfunction in consecutive PCI patients in the
IDEA registry
Stable CAD N745
NSTEACS N456
STEMI N314
-50- -40- -30- -20- -10- -0-
-50- -40- -30- -20- -10- -0-
Age gt70y
diabetes
Chronic Kidney Dys
35
28
28
27
26
23
7.4
5.9
3.8
Savonitto S, et al. Ital Heart J 20056106-118
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Euro Heart Survey 2006
Il medico che cura le malattie croniche-degenerati
ve tratta persone anziane che tuttavia hanno
oggi una lunga aspettativa di vita
6
Age distribution among ACS patients Admitted to
italian CCUs
All NSTEACS patients
All MI patients
H w/o Cath Lab
H with Cath Lab
N patients
patients
27
Di Chiara A, et al Eur Heart J 2003241616-29
Di Chiara A et al, Eur Heart J 200627393-405
7
Età media dei pazienti con IMAOspedale Niguarda
Ca Granda anno 2003
Anni 100- 80- 60- 40- 20- 0-
849
6813
Divisioni Mediche
Dipartimento Cardiologico
8
Valore Prognostico dellEtà nelle Sindromi
Coronariche Acute
N1971 lt30 3 (0.2) 30-3934 (1.7) 40-49155
(7.9) 50-59374 (19) 60-69550
(27.9) 70-79622 (31.6) 80-89213 (10.8) gt90
20 (1.0)
60
50
40
con Morte/(re)IMA a 30 gg
30
20
4 vs 15 RR (IC 95) 3.4 (2.7-4.4)
10
0
100
80
60
40
20
70
Età (anni)
Oltrona L et al, Am Heart J 2004148405-415
9
Euro Heart Survey 2006
10
Elderly with NSTEMI The ROSAI-Elderly Study
30-day Outcomes
Treatments
Conservative Strategy OR 2.31 (1.20-4.48) events
at 30 days
De Servi S, et al. Am Heart J 2004 147 830-836
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Acute Therapies for ACS in the ElderlySubgroup
analyses
Trial Overall Results Age Age Subgroup
Aspirin Aspirin Anti-platelet Trialists 25 RRR MI/Stroke/Death - Similar Benefit gt65
Clopidogrel Clopidogrel CURE 21 RRR MI/Stroke/Death 64 Similar Benefit gt65
GP/IIb/IIIa GP/IIb/IIIa PURSUIT 30 RRR Death/MI (PCI) 64 Similar Benefit gt65
GP/IIb/IIIa GP/IIb/IIIa PRISM PRISM 32RRR Death/MI/SRI 32 RRR Death/MI/SRI 62 63 Similar Benefit gt65 Similar Benefit gt75
LMWH LMWH ESSENCE 16 RRR MI/SRI/Death 64 Similar Benefit gt65
LMWH SYNERGY SYNERGY Similar w/ Heparin 68 None
Early Cath Early Cath Tactics-TIMI 18 Invasive vs Conservative 18 RRR 62 39 RR gt65 56 RR gt75
12
PCI/angio ratio stratified by age
lt55y
55-74y
gt74y
1.0- 0.8- 0.6- 0.4- 0.2- 0.0-
corox
North
PCI
.57
.47
.46
ratio
1.0- 0.8- 0.6- 0.4- 0.2- 0.0-
Centre
.57
.50
.43
1.0- 0.8- 0.6- 0.4- 0.2- 0.0-
South
.56
.50
.46
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Randomised trials of early invasive treatmentin
elderly patients withNSTEACS
Trial Average age pts gt75y Outcome
TIMI IIIB 59 3 Benefit only gt65 y
VANQWISH 61 8 No difference
FRISC II 65 Excluded Benefit only gt65 y
RITA 3 63 No age classes reported Not reported by age
TACTICS 62 12.5 39 RR gt65 56 RR gt75
ICTUS 61 Not reported Trend towards gt benefit gt65y
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http//Elderly.altavianet.it
RCT
Chairmen S. Savonitto, Ospedale Niguarda,
Milano S. De Servi, Ospedale Civile, Legnano
Registry
Patients gt74 years with NSTEACS
ClinicalTrials.gov ID NCT00510185 JCM 2008, in
press
Registry of excluded pts with simplified CRF
Central random
700 pts 40 centers
Early invasive (angio within 48 hours)
Initially conservative (angio for refractory
ischemia)
12-month follow-up
12-month follow-up
12-month follow-up
Primary endpoint the composite of all-cause
mortality, myocardial (re)MI, disabling stroke
and re-hospitalization for cardiovascular causes
or severe bleeding within 6 months
16
Indication for angiography in the initially
conservative arm
ClinicalTrials.gov ID NCT00510185 JCM 2008, in
press
Patients gt74 years With NSTEACS
Web random
Early invasive (angio within 48 hours)
Initially conservative (angio for refractory
ischemia)

• Refractory ischemia recurrent symptoms
• and ECG changes gt12 hrs after admission
• despite maximal therapy
• Post-admission (re)MI
• Heart failure
• Malignant ventricular arrhythmia

Angio During index admission

• Recurrent ischemic symptoms (CCS III-IV)
• after index discharge despite optimal
• antianginal therapy, particularly if ischemia
• is documented on provocative testing

Angio After index discharge
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Main exclusion criteria
ClinicalTrials.gov ID NCT00510185 JCM 2008, in
press

• Secondary causes of myocardial ischemia
• Ongoing ischemia despite maximal anti-ischemic
  rx
• Ongoing signs of heart failure despite treatment
• PCI or surgery within 30 days prior to
  randomization
• Serum creatinine level gt2.5 mg/dL
• High bleeding risk

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Sample size

• Sample size calculations are based on the
  primary-endpoint rates at 6 months in pts gt75y
  observed in the retrospective analysis of the
  TACTICS-TIMI 18 trial.
• In this study, the rates of the primary endpoint
  of death MI rehospitalization were 30 in the
  conservative arm vs 20 in the invasive arm.
• Based upon the logrank test for survival curves.

Two-tailed alpha Power 1 b N per group
0.05 80 252
0.05 85 289
0.05 90 338
N total N per Center (46c)
504 11
578 12.6
676 14.7
ClinicalTrials.gov ID NCT00510185 JCM 2008, in
press
19
Centri al 30 Ottobre 2007
CENTRI PAZ
NORD 18 33
CENTRO 18 31
SUD 21 36
TOTALE 57
1
5
3
5
4
6
2
1
1
8
11
2
2
6
20
Point Prevalence of End Stage Renal Disease
No. patients
2000
2010
1997
304,410
Exponential smoothing model with quadratic trend
R2 99.7, r 0.9995
21
Cardiorenal Risk
Cardiac Disease
Renal Disease
Myocardial Infarction, Heart Failure,
Arrhythmias, and Cardiac Death in the Renal
Patient
Acute Renal Failure and Death in the Cardiac
Patient
22
Major Causes of Acute Renal Failure in Cardiac
Patients

• 1) Radiocontrast Nephropathy (RCN)
• 2) Acute Renal Failure after Cardiopulmonary
  Bypass Procedures

23
The CKMB and PCI study N 2860
20- 15- 10- 5- 0-
12.3
8.9
CKD Incidence
4.5
Investigator Report (sCrgt1.5)1
Corelab sCr Determination (gt1.1 women, gt1.5 men)2
eGFR (lt60 ml)2

1. Cavallini C et al EHJ 2005261494 2. Roghi A et
   al JCM 2007 in press

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Independent predictors of acute renal failure
after PCI The CKMB and PCI study
Variable Wald Chi square Odds Ratio 95 C.I. p-value Predictive information ()
eGFR lt45 ml 45-59.9 ml 60-74.9 ml gt75 ml 12.68 3.00 0.11 3.22 1.69 0.90 1 1.69-6.11 0.93-3.05 0.52-1.58 0.0004 0.083 0.736 33 7.7
Ejection fraction (continuous) 9.79 0.97 0.95-0.99 0.002 25
Hypertension 5.61 1.70 1.10-2.64 0.018 14
Prior CABG 4.48 1.75 1.04-2.92 0.034 12
Fluoroscopy time (continuous) 3.15 1.017 1.00-1.04 0.076 8.1
Roghi A, et al, JCM 2007, in press
25
Incidence of ARF post PCI and impact on mortality
according to definition
30- 25- 20- 15- 10- 5- 0-
21.8
624/2860
Incidence / 2y mortality
11.3
4.8
3.7
106/2860
ARF SCr baseline 0.5 mg/dL
ARF SCr baseline 0.5 mg/dL or 25
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Univariate predictors of acute renal failure
after PCI
No ARF n2754
ARF n106
P value
OR and 95 CI
Age (yrs) 63 66 Female
21.6 23.8 Diabetes 19.3
24.0 eGFR gt75 ml 68.8 56.6
60-74.9 ml 19.4 16.0 45-59.9 ml
8.2 14.2 lt 45 ml 3.4
13.2 Hypertension 59.2
71.2 Hypercholest 57.7
63.2 Previous MI 49.9 56.6 Previous
PCI 21.9 17.9 Previous CABG 9.8 19.8 Atrial
fibrillation 4.8 9.4 History of CHF 4.3 6.6 Prior
stroke or PVD 10.5 18.9 ACS 50.3 50.0 3-vessel
disease 15.5 28.3 Mean EF 54 51 Unsuccessful
PCI 5.0 8.5 Post-PCI CKMB elev 17.1 24.5 Mean
fluorosc. time 12.2 14.4 continuous variables
lt0.02 lt0.01 lt0.0001 lt0.001 lt0.001 lt0.03 lt0
.007 lt0.0008 lt0.0001 0.05 lt0.02
Also mortality predictor
0.25 0.50 0.75 1 2
3 4 5
gt in ARF
ltin ARF
27
Independent Predictors of 2y mortality at Cox
regression analysis the CKMB and PCI study
(n2860)
Variable Wald Chi square Hazard ratio 95 CI p-value Predictive information ()
Age (continuous) 22.43 1.06 1.03-1.08 lt0.0001 25.6
Ejection fraction (continuous) 22.18 0.96 0.94-0.98 lt0.0001 25.3
eGFR lt45 ml 45-59.9 ml 60-74.9 ml gt75 ml 18.10 2.84 0.96 1.07 1 1.66-4.84 0.53-1.75 0.65-1.76 0.0001 0.89 0.79 20.7
Unsuccessful procedure 7.07 2.19 1.23-3.91 0.008 8.1
Atrial fibrillation 5.38 1.89 1.10-3.26 0.02 6.1
Diabetes mellitus 4.53 1.54 1.04-2.30 0.03 5.2
Fluoroscopy time 4.33 1.02 1.00-1.04 0.04 4.9
Acute Renal Failure 3.54 1.83 0.98-3.44 0.06 4.0
Roghi A, et al, JCM 2007, in press
28
Rapporto rischio beneficio dell angioplastica
coronarica
Beneficio
Rischio
In relazione all indicazione e al rischio di base
Danno renale Major bleeding Infarto procedurale
HR 1.81
HR 3.52
HR 1.043 continuous

1. Roghi A, JCM 2007
2. Lincoff AM, JAMA 2004
3. Cavallini C, EHJ 2005

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Bleeding by Renal Function
heparin
bivalirudin
Incidence of major bleeding
None(90 mL/min)
Mild(6089 mL/min)
Moderate(3059 mL/min)
Severe(lt30 mL/min)
Degree of Renal Impairment
Adapted from Robson, J Invas Cardiol. 2000,
12SupplF 33F-36F
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Mortalità a 1 anno pazienti ad alto rischio
?48
?37
?33
?41
Lincoff AM et al. JAMA 2004292696-703
31
Top 10 List DiabetesGlobal Burden of Disease
Study
2O25
1995
Country India China U.S. Russia Japan Brazil Indon
esia Pakistan Mexico Ukrane All Other Total
Millions 19.4 16.0 13.9 8.9 6.3 4.9 4.5 4.3 3.8 3.
6 49.7 135.3
Country India China U.S. Pakistan Indonesia Russia
Mexico Brazil Egypt Japan All Other Total
Millions 57.2 37.6 22.9 14.5 12.4 12.2 11.7 11.6 8
.8 8.5 103.6 300
King H. Diabetes Care 1998211414-31
32
All-Cause Mortality T2DM Verona Diabetes Study
N5818 10-year Follow-up
Brun E. Diabetes Care 200023(8) 1119-1123
33
Trends in Diabetes PrevalenceNRMI
Trend plt0.001
N410,223 20.8 Increase
34
Prevalence of Diabetes in Registries
Study Setting N. Diabets
Italian Registries, year Italian Registries, year Italian Registries, year Italian Registries, year
AICARE-2 2000 ACS 1074 21
BLITZ-1 2001 AMI 1959 22
ROSAI-2 2002 ACS 1581 23
BLITZ-2 2003 IDEA 2003 ACS PCI 1888 1519 27 26
International Registries International Registries International Registries International Registries
OASIS, 1995-6 ACS 8013 21
RIKS-HIA, 1995-8 AMI 5193 20
ICONS, 1998 CRUSADE 2005 AMI ACS 1664 165th 27 33
35
Caratteristiche dei pazienti diabetici 27.3
della popolazione (M24, F33)
Di Chiara A, et al Eur Heart J 200627393-405
Diabete n 515 7010 33 41 50 69 7.7 68 5/41/55
No Diabete n 1373 6612 22 31 31 85 4.0 69 16/54
/30
P lt.0001 lt.0001 .05 lt.0001 lt.0001 .0002 n.s lt.0001
Età media (DS) Precedente cardiopatia
() Precedente BPAC () Precedente Scompenso
() Killip 1 () Creatininemia ingresso gt2 mg/dl
() Marker miocardici elevati () TIMI risk score
(1-2/3-4/5-7) ()
36
Prognostic interactions
LV dysfunction
Renal dysfunction
Diabetes
37
Independent Predictors of 2y mortality at Cox
regression analysis the CKMB and PCI study
(n2860)
Variable Wald Chi square Hazard ratio 95 CI p-value Predictive information ()
Age (continuous) 22.43 1.06 1.03-1.08 lt0.0001 25.6
Ejection fraction (continuous) 22.18 0.96 0.94-0.98 lt0.0001 25.3
eGFR lt45 ml 45-59.9 ml 60-74.9 ml gt75 ml 18.10 2.84 0.96 1.07 1 1.66-4.84 0.53-1.75 0.65-1.76 0.0001 0.89 0.79 20.7
Unsuccessful procedure 7.07 2.19 1.23-3.91 0.008 8.1
Atrial fibrillation 5.38 1.89 1.10-3.26 0.02 6.1
Diabetes mellitus 4.53 1.54 1.04-2.30 0.03 5.2
Fluoroscopy time 4.33 1.02 1.00-1.04 0.04 4.9
Acute Renal Failure 3.54 1.83 0.98-3.44 0.06 4.0
Roghi A, et al, JCM 2007, in press
38
The MUNICH RegistryIntensive diabetes treatment
in ACS
Mortalità Ospedaliera
1999 2001
Età 73 71
Glicata 7,3 7,7
2b/3a 8 52
Coro 51 73
PCI lt24 ore 21 50
Gluc/insulina 0 46
lt0,001
Schnell O, Diabetes Care 2004 27 453-460
39
1-Year Mortality by Diabetic Status in
EPIC-EPILOG-EPISTENT metanalysis
6
6
Diabetes/ABX (n888)
5
Diabetes/PL (n574)
5
4.5
No Diabetes/ABX (n3222)
4
4
No Diabetes/PL (n1850)
Death ()
2.6
3
3
2.5
1.9
2
2
1
1
p0.031
0
0
0
30
60
90
120
150
180
210
240
270
300
330
360
Days from Randomization
Bhatt DL JACC 200035922-928
40
ACUITY TIMING Upstream vs cathlab GPIIb/IIIa RB
in NSTEACS
41
Diabetic Subgroup (n3146)

18
Clopidogrel
17.0
16
CV Death / MI / Stroke
14
12.2
12
HR 0.70Plt0.001
Endpoint ()
Prasugrel
10
NNT 46
8
6
TIMI Major NonCABG Bleeds
Clopidogrel
4
2.6
2.5
2
Prasugrel
0
0
30
60
90
180
270
360
450
Days
42
Mortalità a 1 anno pazienti ad alto rischio
?48
?37
?33
?41
Lincoff AM et al. JAMA 2004292696-703
43
Hospital Mortality Trends By Diabetic StatusNRMI
registries
DM
No DM
Trend plt0.001 for both groups Plt0.001 for DM vs.
No DM decline
Marso S, et al. Am Heart J. 2003145270-7
44
Adjusted Reduction in Mortality 1994-2002NRMI
registries
Trend plt0.001 for all groups Plt0.001 for DM
Women vs. all other groups
Marso S, et al. Am Heart J. 2003145270-7
45
Current trends for high-risk patients in ACS and
PCI Conclusions

• Due to an ageing population and longer survival
  in chronic
• degenerative disease, the cardiologist is
  facing a more complex
• and high-risk population.
• Life expectancy is increasing and demands
  effective therapy
• even in high-risk patients.

46
Current trends for high-risk patients in ACS and
PCI Conclusions

• The risk vs benefit of an aggressive ACS
  treatment in the
• elderly is still under evaluation.
• In Chronic Kidney Disease, the jathrogenic risk
  is high,
• and there are no randomised data showing the
  extent of
• benefit of an invasive approach inACS. There
  are clear
• data showing that cardiologist should primarily
  aim at
• preventing the deterioration of renal function
  in CKD.
• In diabetic patients, there are convincing data
  in favour
• of a more aggressive and comprehensive
  pharmaco-
• interventional approach in ACS, whereas no data
  support
• early revascularization in asymptomatic and
  stable patients.