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