optimale behandlung des kalzifizierten patienten sekund¤r ......

Download Optimale Behandlung des kalzifizierten Patienten Sekund¤r ... Sekund¤r-Pr¤vention: A) Serum Phosphat

Post on 10-Aug-2019

214 views

Category:

Documents

0 download

Embed Size (px)

TRANSCRIPT

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

    B) iPTH in den Zielbereich bringen - durch Kontrolle des S-Phosphates

    - durch aktives Vitamin-D (ohne hohe Dosen) - durch Parathyroidektomie

  • Verschwinden von

    vaskulären Verkalkungen

    12 Monate nach Parathy- reoidektomie

    Verberckmoes R et al; Ann Intern Med 82: 529-533, 1975S Rostand and T Drueke, Kidney Int 1999

  • Veränderungen kardiovaskulärer Verkalkungen nach Parathyreoidektomie in Dialyse-Patienten

    Bleyer AJ et al., Am J Kidney Dis 2005

    n=

    Parathyreoidektomie Keine Parathyreoidekt.

    Mittl. iPTH (pg/ml) Zeit zwischen Scans

    10 10

    926  197 151  232 1,7 Jahre 2,1 Jahre

    -1500

    -1000

    -500

    0

    500

    1000

    1500

    Mittl. S-PO4 (mmol/l) 2,2  2,2 1,6  1,8

    K or

    on ar

    ar te

    rie n-

    V er

    ka lk

    un g

    [J äh

    rli ch

    e S

    co re

    -V er

    än de

    ru ng

    ; S

    pi ra

    l-C T]

    p = 0,03

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

    B) iPTH in den Zielbereich bringen

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

    B) iPTH in den Zielbereich bringen - durch Kontrolle des S-Phosphates

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

    B) iPTH in den Zielbereich bringen - durch Kontrolle des S-Phosphates

    - durch aktives Vitamin-D (ohne hohe Dosen)

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

    B) iPTH in den Zielbereich bringen - durch Kontrolle des S-Phosphates

    - durch aktives Vitamin-D (ohne hohe Dosen) - durch Parathyroidektomie

  • Sekundär-Prävention: A) Serum Phosphat senken - unter Vermeidung einer Calcium-Beladung

    Optimale Behandlung des kalzifizierten Patienten

    B) iPTH in den Zielbereich bringen - durch Kontrolle des S-Phosphates

    - durch aktives Vitamin-D (ohne hohe Dosen) - durch Parathyroidektomie - durch Calcimimetika

  • Floege J et al, NDT 2010

    ADVANCE Studie

    United States 38 centers; n = 130

    Finland 2 centers; n = 6

    Australia 8 centers; n = 18

    Poland 4 centers; n = 21

    Germany 3 centers; n = 8

    Hungary 6 centers; n = 47

    Italy 5 centers; n = 46

    Switzerland 3 centers; n = 16

    Spain 4 centers; n = 11

    Canada 10 centers; n = 38

    France 3 centers; n = 7

    Portugal 2 centers; n = 6

    Russia 2 centers; n = 6

    http://www.cia.gov/cia/publications/factbook/flags/hu-flag.html http://www.cia.gov/cia/publications/factbook/flags/hu-flag.html http://openclipart.org/clipart//signs_and_symbols/flags/europe/finland/finland.svg http://openclipart.org/clipart//signs_and_symbols/flags/europe/finland/finland.svg http://images.google.com/imgres?imgurl=http://www.aaicu.org/images/switzerland-flag-new.gif&imgrefurl=http://www.aaicu.org/&h=256&w=384&sz=2&tbnid=kvj54oREMPsJ:&tbnh=79&tbnw=118&prev=/images?q=switzerland+flag&hl=en&lr=&oi=imagesr&start=2 http://images.google.com/imgres?imgurl=http://www.aaicu.org/images/switzerland-flag-new.gif&imgrefurl=http://www.aaicu.org/&h=256&w=384&sz=2&tbnid=kvj54oREMPsJ:&tbnh=79&tbnw=118&prev=/images?q=switzerland+flag&hl=en&lr=&oi=imagesr&start=2 http://images.google.com/imgres?imgurl=http://www.aaicu.org/images/switzerland-flag-new.gif&imgrefurl=http://www.aaicu.org/&h=256&w=384&sz=2&tbnid=kvj54oREMPsJ:&tbnh=79&tbnw=118&prev=/images?q=switzerland+flag&hl=en&lr=&oi=imagesr&start=2 http://images.google.com/imgres?imgurl=http://www.aaicu.org/images/switzerland-flag-new.gif&imgrefurl=http://www.aaicu.org/&h=256&w=384&sz=2&tbnid=kvj54oREMPsJ:&tbnh=79&tbnw=118&prev=/images?q=switzerland+flag&hl=en&lr=&oi=imagesr&start=2 http://images.google.com/imgres?imgurl=http://www.aaicu.org/images/switzerland-flag-new.gif&imgrefurl=http://www.aaicu.org/&h=256&w=384&sz=2&tbnid=kvj54oREMPsJ:&tbnh=79&tbnw=118&prev=/images?q=switzerland+flag&hl=en&lr=&oi=imagesr&start=2

  • *Randomization was stratified by screening CAC score (≥ 30 to 399, ≥ 400 to 999, and ≥ 1000)

    CAC: coronary artery calcification

    Study population (n=360): • Ca ≥ 8.4 mg/dl • CAC ≥ 30 • iPTH ≥ 300 pg/ml • if iPTH ≤ 300 pg/ml: Ca x P > 50 mg2/dl2

    Cinacalcet Group (cinacalcet + low dose Vit D)

    Control Group (flexible dosing of Vit D)

    1:1 Randomization*

    Floege J et al, NDT 2010

    ADVANCE Studie - Design -

  • Day 1

    30 mg

    60 mg

    90 mg

    120 mg

    W4 W8 W12 W52

    Titration Phase (20 wks)

    W16

    Cinacalcet Group N=165

    Control Group N=165

    Follow up Phase (32 wks)

    W20 W28

    R A N D O M I Z A T I O N

    S C R E E N I N G

    180 mg

    Screening < 45 days

    Floege J et al, NDT 2010

    ADVANCE Studie - Design -

  • • Adults on hemodialysis ≥ 6 months

    • iPTH > 31.8 pmol/L (300 pg/mL) OR

    • iPTH ≥ 15.9 pmol/L (150 pg/mL) and < 31.8 pmol/L (300 pg/mL) and: – Ca x P > 3.9 mmol2/L2 (50 mg2/dL2) – receiving active vitamin D therapy

    • Serum corrected calcium ≥ 2.1 mmol/L (8.4 mg/dL) • Screening CAC score > 30 • On calcium-containing phosphate binder

    Floege J et al, NDT 2010

    ADVANCE Studie - Einschlusskriterien -

  • Floege J et al, NDT 2010

    ADVANCE Studie - Endpunkte -

    • Percentage change from baseline in CAC score at week 52

    •Absolute change in CAC score at week 52 •Absolute and percentage change from baseline in

    – Aortic calcification at week 52 – Aortic valve calcification at week 52 – Laboratory parameters at end of study (weeks 44 through 52)

    •Proportion of patients achieving > 15% progression of CAC at week 52 •Safety

    Secondary Endpoints • Percentage change from baseline in CAC score at week 52

    Primary Endpoint

    Secondary Endpoints

  • Raggi P et al, in revision

    PTH - Absolute Change from Baseline

  • Raggi P et al, in revision

    Ca x P - Absolute Change from Baseline

  • Raggi P et al, in revisionRaggi P et al, in revision

    Weekly Vitamin D Analog Dose (IV Paricalcitol Equivalents) by Treatment Group

  • Anatomic Location

    Cinacalcet (N = 115)

    Median (Q1, Q3) Control Group

    (N = 120) Median (Q1, Q3) p-value

    (CMH statistic)

    Total coronary artery

    n 115 119Total coronary artery

    Agatston* 24 (-1, 63) 31 (8, 81) 0.073 Total coronary artery Volume 22 (2, 52) 30 (10, 78) 0.009

    Thoracic Aorta

    n 80 95 Thoracic Aorta Agatston* 19 (0, 40) 33 (4, 69) 0.055 Thoracic Aorta

    Volume 16 (3, 47) 29 (6, 72) 0.095

    Aortic valve n 56 51

    Aortic valve Agatston* 6 (-16, 41) 52 (-10, 123) 0.014Aortic valve Volume 9 (-19, 38) 35 (-13, 78) 0.035

    Mitral valve n 52 64

    Mitral valve Agatston* 12 (-14, 95) 54 (-4, 178) 0.053Mitral valve Volume 14 (-13, 88) 42 (-11, 125) 0.125

    *Primary and secondary endpoints were based on Agatston scoring methodology and Volume was part of an additional analysis set Note that baseline AC scores =0 were incremented by 1. Note that Percent Change summaries for AVC and MVC exclude patients with a baseline zero (0) score.

    Percent Change in Calcification Scores from Baseline to Week 52

    Raggi P et al, submitted

  • *Primary and secondary endpoints were based on Agatston scoring methodology and Volume was part of an additional analysis set ** Log Transformed Data

    Raggi P et al, in revision

    Forest Plot: Primary & secondary end points

  • Proportion of Patients with > 15% Progression of CAC Score from Baseline to Week 52

    Raggi P et al, submitted

  • Cinacalcet (N=180)

    Control Group

    (N=180)

    All Patients (N=360)

    All adverse events 156 (87) 156 (87) 312 (87) Life-threatening and fatal adverse events 15 (8) 17 (9) 32 (9) Serious adverse events 88 (49) 82 (46) 170 (47) All treatment-related adverse eventsAll treatment-related adverse eventsAll treatment-related adverse eventsAll treatment-related adverse events Related to cinacalcet 53 (29) 0 (0) 53 (15) Related to vitamin D analog 3 (2) 7 (4) 10 (3) All treatment-related life-threatening and fatal adverse eventsAll treatment-related life-threatening and fatal adverse eventsAll treatment-related life-threaten