enzo manzato iperuricemia con deposito di urato: nuovi approcci terapeutici
TRANSCRIPT
Enzo Manzato
Iperuricemia con deposito di urato:nuovi approcci terapeutici
Diabetes Care 32, 153, 2009
anni
HR = 1,30 (IC 95% 1,13-1,51)
Uricemia > 5,1 mg/dl
Uricemia ≤ 5,1 mg/dl
n = 2.910; follow-up 4,4 anni
Diabetes Care 32, 153, 2009
anni
sop
ravviv
en
za
cu
mu
lata
HR = 1,30 (IC 95% 1,13-1,51)
Uricemia > 5,1 mg/dl
Uricemia ≤ 5,1 mg/dl
n = 2.910; follow-up 4,4 anni
Diabetes Care 32, 153, 2009
anni
sop
ravviv
en
za
cu
mu
lata
HR=1,25 (p<0,01)
Sindrome Metabolica NO
Sindrome Metabolica SÌ
HR = 1,30 (IC 95% 1,13-1,51)
Uricemia > 5,1 mg/dl
Uricemia ≤ 5,1 mg/dl
n = 2.910; follow-up 4,4 anni
Cardiovascular Conditions and Risk Factors Associated with Elevated Uric Acid
- Hypertension and prehypertension- Renal disease (including reduced glomerular filtration rate and microalbuminuria) -Metabolic syndrome (including abdominal obesity, hypertriglyceridemia, low level of HDL
cholesterol, insulin resistance, impaired glucose tolerance, elevated leptin level)- Obstructive sleep apnea- Vascular disease (carotid, peripheral, coronary artery)- Stroke and vascular dementia- Preeclampsia- Inflammation markers (CRP, PAI 1 inhibitor , s-ICAM 1)- Endothelial dysfunction- Oxidative stress- Sex and race (postmenopausal women, blacks)- Demographic (movement from rural to urban communities, Westernization, immigration to
Western cultures)
N Engl J Med 359, 1811, 2008
Stroke 37, 1503, 2006
Q1 > 4,22Q2 4,22 - 4,74Q3 4,74 - 5,50Q4 5,50 - 6,41Q5 > 6,41 mg/dl
n = 4.385; follow-up 8,4 anni
Circulation 116, 894, 2007
0
0.2
0.4
0.6
0.8
1
1.2
1.4
MORTALITÁ TOTALE
SENZA PRECEDENTE CHD CON PRECEDENTE CHD
SENZA GOTTA
CON GOTTA
SENZA GOTTA
CON GOTTA
* *
Health Professionals Follow-up Study
n = 51.297; follow-up 12 anni
RISC
HIO
REL
ATIV
O M
ULT
IVAR
IATO
Circulation 116, 894, 2007
0
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
MORTALITÁ TOTALE CARDIO-VASCOLARE
SENZA PRECEDENTE CHD CON PRECEDENTE CHD
SENZA GOTTA
CON GOTTA
SENZA GOTTA
CON GOTTA
**
Health Professionals Follow-up Study
n = 51.297; follow-up 12 anni
RISC
HIO
REL
ATIV
O M
ULT
IVAR
IATO
Diabetes Care 31, 361, 2008
Health Professionals Follow-up Study
n = 4.536; follow-up 10,1 anni
Rischio di diabete aggiustato per età, sesso, IMC, circonferenza vita, pressione arteriosa e colesterolo HDL per quartili di acido urico
p for trend < 0.001
Series10
0.2
0.4
0.6
0.8
1
1.2
1.4
1.6
1.8
≤ 4,49 ≥ 6,23 mg/dl4,50-5,21 5,22-6,22
Risc
hio
rela
tivo
di d
iabe
te
ACIDO URICO
Am J Med 123, 957, 2010
Framingham Heart Study original (n 4883) and offspring (n 4292) cohorts
relative risk of incident diabetes adjusting for age, sex, physical activity, alcohol consumption, smoking, hypertension, body mass index, and blood levels of glucose, cholesterol, creatinine, and triglycerides.
aged 29-62 years at time of recruitment in 1948,followed biennially, 26° examination [2000-2002] for the original cohort
<5,0 5,0-5,9 6,0-6,9 7,0-7,9 <8,00
0.5
1
1.5
2
2.5
mg/dL
rela
tive
risk
of in
cide
nt d
iabe
tes
URIC ACID
Evidence Linking Uric Acid and Hypertension
- An elevated uric acid level consistently predicts the development of hypertension.- An elevated uric acid level is observed in 25–60% of patients with untreated essential
hypertension and in nearly 90% of adolescents with essential hypertension of recent onset.
- Raising the uric acid level in rodents results in hypertension with the clinical, hemodynamic, and histologic characteristics of hypertension.- Reducing the uric acid level with xanthine oxidase inhibitors lowers blood pressure in
adolescents with hypertension of recent onset.
N Engl J Med 359, 1811, 2008
Multivariable-adjusted association of baseline serum uric acid level with incident hypertension
Hypertension 48, 1031, 2006
<4,99 4,99-5,41 5,50-5,90 6,00-6,41 6,51-6,89 >6,990
0.20.40.60.8
11.21.4
mg/dl
uric acid
Rela
tive
risk
p trend = 0,02
n = 2.062; follow-up 21,5 anni
Veterans Administration - Boston
JAMA 300, 924, 2008
n = 30 adolescents (aged 11-17 years) with newly diagnosed essential hypertension and uric acid >6 mg/dl, treated for 4 weeks with allopurinol 200 mg twice daily
JAMA 300, 924, 2008
n = 30 adolescents (aged 11-17 years) with newly diagnosed essential hypertension and uric acid >6 mg/dl, treated for 4 weeks with allopurinol 200 mg twice daily
Lancet 375, 2161, 2010
Change in total exercise time from baseline
n = 65 patients with angiographically documented coronary artery disease
J Clin Invest 120, 1791, 2010
CASO CLINICO
Arch Gerontology Geriat 55, 497, 2012
CASO CLINICO
Arch Gerontology Geriat 55, 497, 2012
Pharm Reviews 58, 87, 2006
N Engl J Med 353, 2450, 2005
Febuxostat 80 mg/day
Febuxostat 120 mg/day
Allopurinol 300 mg/day
0
10
20
30
40
50
60
70
% patients with uric acid <6 mg/dl at last visit%
pati
ents
p < 0.001
N Engl J Med 353, 2450, 2005
Subjects Requiring Treatment for Gout Flares
Arthritis & Rheumatism 59, 1540, 2008
Proportion of subjects with serum urate levels <6.0 mg/dl at final visit
Prop
ortio
n of
sub
ject
s (%
)
Placebo Febuxostat 80 mg/day
Febuxostat 120 mg/day
Febuxostat 240 mg/day
Allopurinol 300 mg/day
0102030405060708090
100
J Rheumatol 36, 1273, 2009
Arthritis Research & Therapy 12, R63, 2010
Effect of baseline characteristics on treatment response
Series10
10
20
30
40
50
60
70
80
90
<9 mg/dl9-10 mg/dl>10 mg/dl
subj
ects
ach
ievi
ng s
UA
<6.0
mg/
dLat
fina
l vis
it (%
)
Febuxostat40 mg/day
n = 757
Febuxostat80 mg/day
n = 756
Allopurinol200/300 mg/day
n = 755
Clinical Therapeutics 35, 180, 2013
Proportion of patientswho achieved sUA < 6.0 mg/dL
Nota 91Determinazione 2 novembre 2010 (GU 12 novembre 2010, n. 265):Modifiche, relative all’inserimento della Nota 91, alla determinazione 4 gennaio 2007 : “Note AIFA 2006-2007 per l’uso appropriato dei farmaci”.
La prescrizione a carico del SSN è limitata alle seguenti condizioni:Trattamento dell'iperuricemia cronica con anamnesi o presenza di tofi e/o di artrite gottosa in soggetti che non siano adeguatamente controllati con allopurinolo o siano ad esso intolleranti.
Lancet 377, 165, 2011
Xanthine oxidase inhibitorsallopurinolfebuxostat