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Iperuricemia con deposito di urato:
nuovi approcci terapeutici
Enzo Manzato
Uricemia ≤ 5,1 mg/dl
Uricemia > 5,1 mg/dl
HR = 1,30 (IC 95% 1,13-1,51)
anni
n = 2.910; follow-up 4,4 anni
Diabetes Care 32, 153, 2009
sopravvivenza cumulata
Uricemia ≤ 5,1 mg/dl
Uricemia > 5,1 mg/dl
HR = 1,30 (IC 95% 1,13-1,51)
anni
n = 2.910; follow-up 4,4 anni
Diabetes Care 32, 153, 2009
sopravvivenza cumulata
Uricemia ≤ 5,1 mg/dl
Uricemia > 5,1 mg/dl
HR = 1,30 (IC 95% 1,13-1,51)
Sindrome Metabolica NO
Sindrome Metabolica SÌ
HR=1,25 (p<0,01)
anni
n = 2.910; follow-up 4,4 anni
Diabetes Care 32, 153, 2009
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
Q1
Q2
Q3
Q4
Q5
> 4,22
4,22 - 4,74
4,74 - 5,50
5,50 - 6,41
> 6,41 mg/dl
n = 4.385; follow-up 8,4 anni
Stroke 37, 1503, 2006
Health Professionals Follow-up Study
MORTALITÁ TOTALE
RISCHIO RELATIVO MULTIVARIATO
1.4
*
1.2
*
1
0.8
0.6
0.4
0.2
0
SENZA
GOTTA
CON
GOTTA
SENZA PRECEDENTE CHD
SENZA
GOTTA
CON
GOTTA
CON PRECEDENTE CHD
n = 51.297; follow-up 12 anni
Circulation 116, 894, 2007
Health Professionals Follow-up Study
RISCHIO RELATIVO MULTIVARIATO
MORTALITÁ TOTALE
CARDIOVASCOLARE
1.6
*
1.4
*
1.2
1
0.8
0.6
0.4
0.2
0
SENZA
GOTTA
CON
GOTTA
SENZA PRECEDENTE CHD
SENZA
GOTTA
CON
GOTTA
CON PRECEDENTE CHD
n = 51.297; follow-up 12 anni
Circulation 116, 894, 2007
Health Professionals Follow-up Study
Rischio di diabete aggiustato per età, sesso, IMC, circonferenza vita,
pressione arteriosa e colesterolo HDL per quartili di acido urico
Rischio relativo di diabete
1.8
1.6
1.4
1.2
1
0.8
0.6
0.4
0.2
0
≤ 4,49
p for trend < 0.001
n = 4.536; follow-up 10,1 anni
4,50-5,21
5,22-6,22
≥ 6,23 mg/dl
ACIDO URICO
Diabetes Care 31, 361, 2008
Framingham Heart Study original (n 4883) and offspring (n 4292) cohorts
aged 29-62 years at time of recruitment in 1948,
followed biennially, 26° examination [2000-2002] for the original cohort
relative risk of incident diabetes
2.5
2
1.5
1
0.5
0
<5,0
5,0-5,9
6,0-6,9
URIC ACID
7,0-7,9
<8,0 mg/dL
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.
Am J Med 123, 957, 2010
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
Veterans Administration - Boston
Multivariable-adjusted association of baseline
serum uric acid level with incident hypertension
p trend = 0,02
1.4
Relative risk
1.2
1
0.8
0.6
0.4
0.2
0
<4,99
4,99-5,41 5,50-5,90 6,00-6,41 6,51-6,89
>6,99 mg/dl
uric acid
n = 2.062; follow-up 21,5 anni
Hypertension 48, 1031, 2006
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
JAMA 300, 924, 2008
Change in total exercise time from baseline
n = 65 patients with angiographically documented coronary artery disease
Lancet 375, 2161, 2010
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
% patients with uric acid <6 mg/dl at last visit
70
% patients
60
p < 0.001
50
40
30
20
10
0
Febuxostat 80
mg/day
Febuxostat 120
mg/day
Allopurinol 300
mg/day
N Engl J Med 353, 2450, 2005
Subjects Requiring Treatment for Gout Flares
N Engl J Med 353, 2450, 2005
Proportion of subjects (%)
Proportion of subjects with serum urate levels <6.0 mg/dl at final visit
100
90
80
70
60
50
40
30
20
10
0
Placebo
Febuxostat 80
mg/day
Febuxostat 120 Febuxostat 240 Allopurinol 300
mg/day
mg/day
mg/day
Arthritis & Rheumatism 59, 1540, 2008
J Rheumatol 36, 1273, 2009
Effect of baseline characteristics on treatment response
subjects achieving sUA <6.0 mg/dL
at final visit (%)
90
80
70
60
<9 mg/dl
50
9-10 mg/dl
40
>10 mg/dl
30
20
10
0
Febuxostat
40 mg/day
n = 757
Febuxostat
80 mg/day
n = 756
Allopurinol
200/300 mg/day
n = 755
Arthritis Research & Therapy 12, R63, 2010
Proportion of patients
who achieved sUA < 6.0 mg/dL
Clinical Therapeutics 35, 180, 2013
Nota 91
Determinazione 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.
Xanthine oxidase inhibitors
allopurinol
febuxostat
Lancet 377, 165, 2011