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Kaliumhaushalt bei Herzinsuffizienz Neue Therapieoptionen Martin Hülsmann

Enteraler Kaliumhaushalt Dünndarmresorption passiv parazellulär ATP-Transporter H+/K+ Dickdarmsekretion Na+/K+-ATPase ( Aldosteronvermittelt)

Ursachen einer Hyperkaliämie Niereninsuffzienz Kaliumsparende Diuretika ACE-Hemmer/ARB Spironolacton/Eplerenon M.Addison Zellzerfall ( Myolyse, Tumorzerfall,Trauma)

Folgen einer Hyperkaliämie Muskelschwäche Muskelzittern EKG: spitze hohe T, flaches p, Verbreiterung des QRS-Komplex Kammerflimmern/Asystolie

RALES-Trial: Spironolactone Chronic heart failure NYHA III, IV ACE-I + loop diuretic LVEF <35% Mortality –30% Pitt, B. et al. N Engl J Med 1999;341:709-717 Mineralokortikoid-Rezeptor Antagonist

P<0.0001

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ACE-I in HF: Mortality reduction CONSENSUS severe CHF n=253 RRR=-27% SOLVD mild or moderate CHF n=2569 RRR=-16% Placebo Enalapril NEJM 1987 NEJM 1991

Therapieoptionen Akut: Intermediäre Langzeittherapie: Calcium Gluconat Insulin/Glucose Beta-Agonisten Intermediäre Dialyse Schleifendiuretika Thiaziddiuretika Natrium Bicarbonat bei metaboler Azidose ( pH<7.35 Bicarbonat <20) Langzeittherapie: Diät Reduktion von RAAS-Antagonisten ( ACE-Hemmer, ARB MRA) Kaliumbinder

Resonium sulfoniertes Stydrol-Diviynilbenzol-Copolymer Kunstharz Natrium-Kalium Austauscher Wirkung im Dickdarm Effektivität unklar

Evidenz 14 Patientenm it CKD retrospektiv 289 Monate Clin Cardiol. 2012 Jan;35(1):32-6.

Difference of Mean Serum K (95% CI) Efficacy outcomes Outcomes SPS (n=15) Placebo (n=16) Difference of Mean Serum K (95% CI) P Value Serum potassium level at baseline, mEq/La 5.26±0.22 5.23±0.22 0.73 Serum potassium level at final follow-up, mEq/La 3.99±0.56 5.03±0.34 <0.001 Variation of serum potassium, mEq/La −1.25±0.57 −0.21±0.29 −1.04 (−1.37 to −0.71) Normokalemia, no. (%) 11 (73.0) 6 (38.0) 0.07 Lepage et al Clin J Am Soc Nephrol 2015 Dec 7;10(2):2136-2142

Lepage et al Clin J Am Soc Nephrol 2015 Dec 7;10(2):2136-2142 Safety outcomes Outcomes SPS (n=16) Placebo (n=16) P Value Nausea, no. (%) 4 (25.0) 2 (12.5) 0.65 Vomiting, no. (%) 1 (6.3) >0.99 Constipation, no. (%) 6 (37.5) 0.70 Diarrhea, no. (%) 8 (50.0) 0.27 Electrolyte disturbances, no. (%)a Hypokalemia (<3.5 mEq/L) 3 (18.8) 0.23 Hypernatremia (>140 mEq/L) N/A Hypophosphatemia (<2.17 mg/dl) Hypocalcemia (<8.48 mg/dl) Hypomagnesemia (<1.4 mEq/L) 5 (31.2) 0.17 Any adverse event, no. (%) 12 (75.0) 10 (58.8) 0.47 Lepage et al Clin J Am Soc Nephrol 2015 Dec 7;10(2):2136-2142

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Patiromer ( Veltassa®) Vernetztes Polymer als Calcium Salz Versetzt mit Sorbitol Tauscht Calcium gegen Kalium asu

Original Article Patiromer in Patients with Kidney Disease and Hyperkalemia Receiving RAAS Inhibitors Matthew R. Weir, M.D., George L. Bakris, M.D., David A. Bushinsky, M.D., Martha R. Mayo, Pharm.D., Dahlia Garza, M.D., Yuri Stasiv, Ph.D., Janet Wittes, Ph.D., Heidi Christ-Schmidt, M.S.E., Lance Berman, M.D., Bertram Pitt, M.D., for the OPAL-HK Investigators N Engl J Med Volume 372(3):211-221 January 15, 2015

Baseline Demographic and Clinical Characteristics. Table 1 Baseline Demographic and Clinical Characteristics. Weir MR et al. N Engl J Med 2015;372:211-221

Serum Potassium Levels over Time during the Initial Treatment Phase. Figure 1 Serum Potassium Levels over Time during the Initial Treatment Phase. Values are the observed mean values as measured in a central laboratory. During the 4-week initial treatment phase, all patients received treatment with patiromer; patients with a potassium level of 5.1 to less than 5.5 mmol per liter (mild hyperkalemia) received 4.2 g of patiromer twice daily, and those with a potassium level of 5.5 to less than 6.5 mmol per liter (moderate-to-severe hyperkalemia) received 8.4 g of patiromer twice daily. I bars indicate standard errors. Data points are staggered to make them more legible. Weir MR et al. N Engl J Med 2015;372:211-221

Time to First Recurrence of Hyperkalemia during the Randomized Withdrawal Phase. Figure 2 Time to First Recurrence of Hyperkalemia during the Randomized Withdrawal Phase. Shown is the time to the first occurrence of a serum potassium level of 5.5 mmol per liter or higher (Panel A) and of 5.1 mmol per liter or higher (Panel B) among patients who were randomly assigned to continue patiromer treatment and those who were assigned to switch to placebo for the randomized withdrawal phase. Baseline refers to week 0 of the randomized withdrawal phase (week 4 of the study). The dose of the study drug was intended to be kept stable (i.e., not adjusted), and the doses of renin–angiotensin–aldosterone system (RAAS) inhibitors were not to be changed during the first 4 weeks of the randomized withdrawal phase in order to facilitate interpretation of the primary end point in this phase. After week 4 of the randomized withdrawal phase, an increase in the dose of patiromer was allowed at the first occurrence of a serum potassium level of 5.1 mmol per liter or higher. Weir MR et al. N Engl J Med 2015;372:211-221

Primary Efficacy End Point in the Randomized Withdrawal Phase, According to Subgroup. Figure 3 Primary Efficacy End Point in the Randomized Withdrawal Phase, According to Subgroup. Shown is the difference between the placebo group and the patiromer group in the median change in serum potassium levels from the start of the randomized withdrawal phase to week 4 of that phase. The P values for interaction were calculated with the use of two-sided t-tests for the comparison of the differences between placebo and patiromer in the median change within each subgroup. EU denotes European Union. Weir MR et al. N Engl J Med 2015;372:211-221

Adverse Events during the Initial Treatment Phase and through the Safety Follow-up Period for That Phase. Table 2 Adverse Events during the Initial Treatment Phase and through the Safety Follow-up Period for That Phase. Weir MR et al. N Engl J Med 2015;372:211-221

Adverse Events during the Randomized Withdrawal Phase and through the Safety Follow-up Period for That Phase. Table 3 Adverse Events during the Randomized Withdrawal Phase and through the Safety Follow-up Period for That Phase. Weir MR et al. N Engl J Med 2015;372:211-221

Einschlußkriterien: GFR <60 und/oder Hyperkaliämie in der Anamnese

Zusammenfassung Die Herzinsuffizienz ist ein prinzipiell hypokaliämes Zustandsbild Aufgrund der begleitenden Niereninsuffizienz und der Basistherapie nimmt mit der Schwere der Erkrankung die Rate an Hyperkaliämien zu Aufgrund dessen können 30% der HI-Patienten nicht mit der Standardtherapie versorgt werden. Mit Patiromer steht uns hoffentlich ab 2017 ein effektiver und verträglicher Kaliumsenker zur Verfügung

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