AGGIORNAMENTI CARDIO‐METABOLICI
Controllo lipidico ottimale nell’anziano:
i benefici della doppia inibizione
Enzo Manzato (Padova)
Prevalence of lipid lowering drugs
<70 anni
>85 anni
88%
50%
“Salute e benessere dell’anziano”
archivi ASL, 440.000 assistiti
Int J Cardiol 111, 12, 2006
Prevalence of the reasons for non-prescription of statins
Int J Cardiol 111, 12, 2006
Age heterogeneity: fact or fiction?
The fate of diversity in gerontological research.
Gerontologist 32, 17, 1992
31.455 elderly AMI survivors between 1999 and 2003 in Ontario
JAMA 297, 177, 2007
31.455 elderly AMI survivors between 1999 and 2003 in Ontario
JAMA 297, 177, 2007
ricoverati per IMA di età ≥ 80 anni
Register of Information and Knowledge
About Swedish Heart Intensive Care
Admissions (RIKS-HIA)
J Am Coll Cardiol 55, 1362, 2010
Register of Information and Knowledge
About Swedish Heart Intensive Care
Admissions (RIKS-HIA)
J Am Coll Cardiol 55, 1362, 2010
Register of Information and Knowledge
About Swedish Heart Intensive Care
Admissions (RIKS-HIA)
J Am Coll Cardiol 55, 1362, 2010
Register of Information and Knowledge
About Swedish Heart Intensive Care
Admissions (RIKS-HIA)
J Am Coll Cardiol 55, 1362, 2010
Register of Information and Knowledge
About Swedish Heart Intensive Care
Admissions (RIKS-HIA)
J Am Coll Cardiol 55, 1362, 2010
Age heterogeneity: fact or fiction?
The fate of diversity in gerontological research.
Gerontologist 32, 17, 1992
Men and women aged about 40–80 years with non-fasting blood total
cholesterol concentrations of at least 135 mg/dL were eligible
Effects of simvastatin allocation on first major vascular event
Lancet 360, 7, 2002
BREVE
ACCANIMENTO
TERAPEUTICO
ASPETTATIVA
DI VITA
PREVENZIONE
LUNGA
BREVE
LUNGO
TEMPO NECESSARIO PER AVERE
EFFETTI BENEFICI
Men and women aged about 40–80 years with non-fasting blood total
cholesterol concentrations of at least 135 mg/dL were eligible
Effects of simvastatin allocation on first major vascular event
Lancet 360, 7, 2002
Lancet 366, 1267, 2005
Speranza di vita a 65 anni nel Veneto nel 2007
25
17,4
Anni
20
15
21,4
16%
2,8
10
14,6
5
Con
disabilità
4,2
Senza
disabilità
17,2
20%
0
Maschi
Femmine
ASPETTATIVA DI VITA
Aspettativa di vita
DONNE
UOMINI
20
15
15
15,7
12,4
11,9
9,3
10
8,6
10
6,7
5,9
5
70
75
80
ETÀ
85
3,9
90
4,7
5
2,7
95
70
75
80
ETÀ
85
3,2
90
2,3
95
Lancet 366, 1267, 2005
Databases within the New England Veterans
Integrated Service Network (VISN-1)
Circulation 120, 1491, 2009
Proportions of Subjects Who Had an Acute Myocardial
Infarction or Underwent Revascularization
Circulation 120, 1491, 2009
Proportions of Subjects Who Had an
Acute Myocardial Infarction or Underwent Revascularization
Circulation 120, 1491, 2009
Lancet 376, 1670, 2010
LA DOPPIA INIBIZIONE DELL’ASSORBIMENTO
E DELLA SINTESI DEL COLESTEROLO
raddoppio la dose
dose iniziale di
statina
dose iniziale di
simvastatina
0
10
+6% +6% +6%
+ Ezetimibe
10 mg
20
30
40
50
% riduzione del colesterolo LDL
INIBIZIONE
DELLA SINTESI
DOPPIA INIBIZIONE
60
< 77 mg/dl
< 155 mg/dl
Int J Clin Pract 64,1052, 2010
Int J Clin Pract 64,1052, 2010
Am J Cardiol 106, 1255, 2010
SHARP: Eligibility
• History of chronic kidney disease
– not on dialysis: elevated creatinine on 2 occasions
• Men: ≥1.7 mg/dL (150 µmol/L)
• Women: ≥1.5 mg/dL (130 µmol/L)
– on dialysis: haemodialysis or peritoneal dialysis
• Age ≥40 years
• No history of myocardial infarction or
coronary revascularization
• Uncertainty: LDL‐lowering treatment not
definitely indicated or contraindicated
SHARP: Assessment of LDL‐
lowering
SHARP: Major Atherosclerotic Events
Proportion suffering event (%)
25
Risk ratio 0.83 (0.74 – 0.94)
Logrank 2P=0.0022
20
Placebo
15
Eze/simv
10
5
0
0
1
2
3
Years of follow‐up
4
5
SHARP
32 mg/dL
Lancet 366, 1267, 2005
Proportional reduction in
atherosclerotic event rate (95% CI)
30%
Statin vs control
(21 trials)
25%
20%
More vs Less
(5 trials)
15%
SHARP
32 mg/dL
10%
5%
0%
0
10
20
30
Mean LDL cholesterol difference
between treatment groups (mg/dL)
40
Lancet 376, 1670, 2010
Proportional reduction in
atherosclerotic event rate (95% CI)
30%
Statin vs control
(21 trials)
25%
20%
SHARP
17% risk
reduction
More vs Less
(5 trials)
15%
10%
5%
0%
0
10
20
30
Mean LDL cholesterol difference
between treatment groups (mg/dL)
40
Lancet 376, 1670, 2010
SHARP: Major Vascular Events
Event
Eze/simv
(n=4650)
Placebo
(n=4620)
Major coronary event
Non‐haemorrhagic stroke
Any revascularization
213 (4.6%) 230 (5.0%)
131 (2.8%) 174 (3.8%)
284 (6.1%) 352 (7.6%)
Major atherosclerotic event
526 (11.3%) 619 (13.4%)
Other cardiac death
Haemorrhagic stroke
162 (3.5%) 182 (3.9%)
45 (1.0%) 37 (0.8%)
Risk ratio & 95% CI
16.5% SE 5.4
reduction
(p=0.0022)
Other major vascular events 207 (4.5%) 218 (4.7%)
5.4% SE 9.4
reduction
(p=0.57)
Major vascular event
15.3% SE 4.7
reduction
(p=0.0012)
701 (15.1%) 814 (17.6%)
0.6
0.8
Eze/simv
better
1.0
1.2
1.4
Placebo
better
FINESTRA TERAPEUTICA
REAZIONI AVVERSE
ETÀ
SHARP: Safety
Eze/simv Placebo
(n=4650) (n=4620)
Myopathy
CK >10 x but ≤40 x ULN
CK >40 x ULN
17 (0.4%)
4 (0.1%)
16 (0.3%)
5 (0.1%)
Hepatitis
Persistently elevated ALT/AST >3x ULN
21 (0.5%)
30 (0.6%)
18 (0.4%)
26 (0.6%)
Complications of gallstones
Other hospitalization for gallstones
85 (1.8%)
21 (0.5%)
76 (1.6%)
30 (0.6%)
Pancreatitis without gallstones
12 (0.3%)
17 (0.4%)
SHARP: Cancer incidence
Proportion suffering event (%)
25
20
Risk ratio 0.99 (0.87 – 1.13)
Logrank 2P=0.89
15
Eze/simv
Placebo
10
5
0
0
1
2
3
Years of follow‐up
4
5
SHARP: Conclusions
• No increase in risk of myopathy, liver and biliary
disorders, cancer, or nonvascular mortality
• No substantial effect on kidney disease progression
• Two‐thirds compliance with eze/simv reduced the risk
of major atherosclerotic events by 17% (consistent
with meta‐analysis of previous statin trials)
• Similar proportional reductions in all subgroups
(including among dialysis and non‐dialysis patients)
• Full compliance would reduce the risk of major
atherosclerotic events by one quarter, avoiding
30–40 events per 1000 treated for 5 years
Controllo lipidico ottimale nell’anziano:
i benefici della doppia inibizione
IMPORTANTI
EFFETTI
COLLATERALI
MODESTI
MODESTI
EFFETTI
BENEFICI
IMPORTANTI
Controllo lipidico ottimale nell’anziano:
i benefici della doppia inibizione
MIGLIORE
QUALITÀ
DI VITA
PEGGIORE
MODESTI
EFFETTI
BENEFICI
IMPORTANTI
Controllo lipidico ottimale nell’anziano:
i benefici della doppia inibizione