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No. (%) by total cholesterol, mg/dl Normo/Hypercholesterolemia
<164 165-188 189-220 >220 <230 >=230 p
All-cause mortality
52 (67.5) 54 (72.0) 44 (57.9) 48 (63.2) 114 (69.5)
84 (60.0)
<0.05
CHD mortality
23 (29.9) 26 (34.7) 20 (26.3) 21 (27.6) 53 (34.6)
37 (29.8)
<0.05
304 patients (192 men, mean age 73.3+-5.7 years), mean survival time 1758.1+- 113.8 days
Cholesterol and long-term mortality after acute myocardial infarction in elderly patients
Age and Ageing 1999; 28: 313-315
Mario Bo, Umberto Fiandra, Gianfranco Fonte, Marco Bobbio, Fabrizio Fabris
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Prospective cohort study, 5570
adults aged 55 to 99 years,
mean follow up 13.9 years
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CONCLUSION: Low
cholesterol level is a robust
predictor of mortality in the
nondemented elderly and may be
a surrogate of frailty or
subclinical disease…
Cumulative
mortality.5
.4
.3
.2
.1
0.0
2 4 6 8 years
Participants taking lipid-
lowering drugs were only
one-quarter as likely to die
as those not taking drugs
<175 176-199
200-226
>226
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Il 42% degli eventi si
verifica nei pazienti con
precedente malattia CV
(10.4% della popolazione)
I pazienti con precedente malattia CV hanno un rischio assoluto di eventi
CV del 20% maggiore dei pazienti senza precedenti CV…quasi la metà
degli eventi si verificano negli individui con precedenti clinici CV. Questi
pazienti dovrebbero avere la maggior priorità per un’aggressiva
prevenzione CV..
Il 58% degli eventi si verifica
nei soggetti senza precedenti
clinici (89.6% della
popolazione)
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…all individuals presenting with an acute vascular event of any type in any arterial
territory irrespective of age in a population of 91106 in Oxfordshire, UK, in 2002-05
…2024 acute vascular events occurred in 1657 individuals: 918 (45%)
cerebrovascular (618 stroke, 300 TIA); 856 (42%) coronary vascular (159 STEMI,
316 NSTEMI, 218 UA, 163 SCD); 188 (9%) peripheral vascular (43 aortic, 53
embolic visceral or limb ischemia, 92 critical limb ischemia)…event and incidence
rates rose steeply with age in all arterial territories, with 80% cerebrovascular, 73%
coronary and 78% peripheral vascular events in 12886 (14%) individuals aged
65 years or older; and 54%, 47% and 56%, respectively, in the 5919 (6%) aged
75 years or older….although case fatality rates increased with age, 47% of non-
fatal events occurred at age 75 years or older
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65+ year older (mean age 78.5 years) MI survivors
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CHD, non-fatal MI, fatal/non fatal stroke
CHD death or non-fatal MI
Fatal/non-fatal stroke
5804 patients (2804 men), 70-82 years with
history of, or risk factors for, vascular disease
Pravastatin 40 mg/day vs placebo, follow-up
3.2 years
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9 trials, 19569
pazienti, range età
basale 65-82 anni
RRR 22%, NNT 28
(A)
(B)
RRR 30%, NNT 34
Bayesian Forest Plot for All-Cause Mortality (A)
and Coronary Heart Disease Mortality (B)Bayesian Forest Plot for Non-Fatal MI (C)
RRR 26%, NNT 28
(C)
RRR 25%, NNT 58
Bayesian Forest Plot for Stroke (D)
(D)
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Studio osservazionale su 7220 pazienti con CAD definita angiograficamente, seguiti per
un periodo di 3.3 anni in relazione all’uso di statine in rapporto all’età
Mortalità in pazienti che assumevano
(colonne bianche) e non assumevano
(colonne nere) statine
Analisi multivariata dell’effetto delle
statine sulla mortalità complessiva
nei pazienti di 80+ anni
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Studio osservazionale su pazienti >80 anni con diagnosi di IMA tra il 1999 e il 2003. Analisi di sopravvivenza ed eventi in relazione all’uso di statine sul campione totale (popolazione A, 14907 pazienti) e dopo aver escluso quelli deceduti entro 14 giorni (popolazione B) ed entro un anno (popolazione C)
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35903 Get With the Guidelines-CAD patients aged >=65 years (median age 76.2), 24367 of whom (67.9%) discharged on statin; propensity score weighting analysis
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Retrospective observational study
on 2597 community-dwelling
patients (mean age 84 years) with
a previous hospitalization for CAD
In conclusion, in community-dwelling frail older patients with CAD, statin treatment was significantly
associated with reduced 3-year mortality rate irrespective of age and multidimensional impairment,
although the frailest patients were less likely to be treated with statins
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Recommendations for the treatment of dyslipidemia in older adults
Treatment with statins is recommended for older adults with established CVD in the same way as for younger patients I
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In individuals with clinical ASCVD >75 years of age it is
reasonable to evaluate the potential for ASCVD risk-
reduction benefits and for adverse effects, DDIs and to consider
patient preferences, when initiating a moderate or high-
intensity statin.
NHLBIExpert opinion
ACC/AHA
COR IIa
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Clinical Pharmacokinetics of STATINS
Tmax
hours
Bioav
%
Lipophil Protein
bind.
Metab.
pathw.
Active
metab.
T 1/2
hours
Urinary/
Fecal
excret.
ATORVA 2-3 12 Yes 80-90 CYP 3A4 Yes 15-30 2/70
FLUVA 0.5-1 20-30 Yes >99 CYP 2C9 No 0.5-2 6/90
PRAVA 1-1.5 18 No 43-55 Sulfation No 1-3 20/71
SIMVA 1-2.5 5 Yes 94-98 CYP 3A4/5 Yes 2-3 13/58
ROSUVA 3 20 No 88 CYP 2C9 Yes
(minor)
21 10/90
Pharmacol.Ther. 1999, 84, 413-428 J.Clin.Pharmacol. 2002, 42, 963-970
CYP3A4
Amiodarone
Clarithromicin, Erythromicin
Cyclosporine
Diltiazem, Nifedipine, Verapamile, Lacidipine
Itraconazole, Ketoconazole
Midazolam
Nefazodone
Quinidine
Sildenafil
Warfarin
CYP2C9
Alprenolol
Diclofenac
Fluvastatin
Phenitoin
Tolbutamide
Warfarin
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..il rischio di rabdomiolisi è principalmente determinato dalla dose di statina
piuttosto che dall’entità della riduzione del colesterolo LDL…
.. il maggior determinante del beneficio associato all’uso delle statine è
l’entità della riduzione del colesterolo LDL piuttosto che il tipo o la dose di
statina usata… il maggior determinante della tossicità (peraltro assai
modesta) delle statine non è l’entità della riduzione del colesterolo LDL quanto
la dose di statina usata… sembra pertanto prudente non usare dosi di
statine superiori a quelle necessarie a raggiungere l’obiettivo LDL
desiderato
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Major CV events
In-hospital death
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Statine non compaiono nei criteri di BeersStatine non compaiono nei criteri STOPStatine non compaiono nei criteri PRISCUSStatine compaiono classe A nei criteri FORTA per pazienti con CAD
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Età
estremamente
avanzata e/o
ridotta
spettanza di
vita
Severe
comorbilità
irreversibili
Dipendenza e non
autonomia
Le statine nel paziente anziano con CAD:
NOa tutti e per sempre?
SI’
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…one size
does not
fit all…
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