Lifestyle Changes RF-management: Guidelines. Wie viel Salz ist zuviel? Prävalenz der Hypertonie und Hypercholesterinämie

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Eunice Parrish
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RF-management: Guidelines Prävalenz der Hypertonie und Hypercholesterinämie

management in England 1994-2011 Lifestyle Changes Avoid use of and exposure

healthy diet: Choose and prepare foods with little or no salt Reduction of

Choose whole-grain, high-fiber foods Eat fish, especially oily fish, at

physically active Falaschetti E et al: Lancet 2014 Mod.

1 RF-management: Guidelines Prävalenz der Hypertonie und Hypercholesterinämie Georg Noll HerzKlinik Hirslanden BMJ 2005;330: Hypertension management in England Lifestyle Changes Avoid use of and exposure to tobacco products Consume alcohol only in moderation Consume overall healthy diet: Choose and prepare foods with little or no salt Reduction of sodium from 200 to 100 mmol/d Eat a diet rich in fruit and vegetables Choose whole-grain, high-fiber foods Eat fish, especially oily fish, at least 2 times a week Decrease in saturated and total fat intake Be physically active Falaschetti E et al: Lancet 2014 Mod. after Recommendations by ESC 2005 and AHA 2006 Wie viel Salz ist zuviel? 1. >3 g/d 2. >6 g/d 3. >10 g/d 4. egal N Engl J Med

NaCl-Ausscheidung im Urin (g/24std) 17.11.2015 Estimated Sodium Excretion and Risk of Major Cardiovascular Events PURE Salt Excretion in Switzerland 10.7 10.3 10.5 10.

2 g NaCl) was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake.

8 O Donnell M et al: N Engl J Med 2014 Chappuis A et al: BAG 2011 Pharmakotherapie der arteriellen Hypertonie Aged under 55 years Aged over 55 years or black person of African or Caribbean origin of

2 NaCl-Ausscheidung im Urin (g/24std) Estimated Sodium Excretion and Risk of Major Cardiovascular Events PURE Salt Excretion in Switzerland CONCLUSIONS In this study in which sodium intake was estimated on the basis of measured urinary excretion, an estimated sodium intake between 3 g per day (=7.6 g NaCl) and 6 g per day (=15.2 g NaCl) was associated with a lower risk of death and cardiovascular events than was either a higher or lower estimated level of intake. As compared with an estimated potassium excretion that was less than 1.50 g per day, higher potassium excretion was associated with a lower risk of death and cardiovascular events O Donnell M et al: N Engl J Med 2014 Chappuis A et al: BAG 2011 Pharmakotherapie der arteriellen Hypertonie Aged under 55 years Aged over 55 years or black person of African or Caribbean origin of any age RAS-Hemmer ß-Blocker Ca ++ -Antagonist Diuretikum 2015 Step 1 Step 4 A Step Zielwert 2 für alle A + C<140/90 mmg ausser: Step Diabetiker 3 A + <140/85 C + D mmhg >80J Start 160 Ziel <150 mmhg C Resistant hypertension consider further diuretic alpha or betablocker consider seeking expert advise NICE 2011 A=ACEI or ARB C=CCB D=Thiazide diuretic Aged under 55 years Aged over 55 years or black person of African or Caribbean origin of any age Prevalence of resistant hypertension Observational studies Step 1 A C Step 2 A + C Step 3 Step 4 A + C + D Resistant hypertension consider further diuretic alpha or betablocker consider seeking expert advise A=ACEI or ARB C=CCB D=Thiazide diuretic Randomized Trials NICE 2011 Achelrod D et al: Am J Hypertens

Was bei therapieresistenter Hypertonie? Effects of spironolactone on blood pressure in ASCOT N=1411/19257 (=7.3%) 1. Doxazosin 2. LCZ696 (Entresto) 3.

Nierennervenablation Champam N et al: Hypertension 2007 Spironolactone for resistant hypertension (PATHWAY-2) Pts on treatment for at least 3 months

hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3) Office systolic Blood Pressure Glucose Tolerance Potassium (n=132) (n=133)

origin of any age Step 1 A Step Zielwert 2 für alle A + C<140/90 mmg ausser: Step Diabetiker 3 A + <140/85 C + D mmhg A=ACEI or ARB C=CCB >80J Start

3 Was bei therapieresistenter Hypertonie? Effects of spironolactone on blood pressure in ASCOT N=1411/19257 (=7.3%) 1. Doxazosin 2. LCZ696 (Entresto) 3. Schleifendiuretikum 4. Spironolacton 5. Nierennervenablation Champam N et al: Hypertension 2007 Spironolactone for resistant hypertension (PATHWAY-2) Pts on treatment for at least 3 months with maximally tolerated doses of three drugs These had to be an ACE inhibitor or an ARB, a CCB, and diuretic Effects of amiloride and hydrochlorothiazide on glucose tolerance and blood pressure (PATHWAY-3) Office systolic Blood Pressure Glucose Tolerance Potassium (n=132) (n=133) (n=134) Williams B et al: Lancet 2015 Brown MJ et al: Lancet 2015 Aged under 55 years Aged over 55 years or black person of African or Caribbean origin of any age Step 1 A Step Zielwert 2 für alle A + C<140/90 mmg ausser: Step Diabetiker 3 A + <140/85 C + D mmhg A=ACEI or ARB C=CCB >80J Start 160 Ziel <150 mmhg D=Thiazide diuretic Resistant hypertension Step 4 consider further diuretic alpha or betablocker???????? consider seeking expert advise C N 9361 Age 67.9 y >75 y 28 % CKD 28 % CVD 20 % Framingham Risk >15% 61% Baseline BP (mmhg) 140/78 Statins 43 % Aspirin 51 % NICE

Intensive versus Standard Blood-Pressure Control 136.

26 years Effects of intensive versus standard blood-pressure

blood-pressure control on mortality Effects of intensive

Effects of intensive blood pressure lowering vs ACCORD

4 Intensive versus Standard Blood-Pressure Control mmhg (goal <140 mmhg) Stopped early after 3.26 years Effects of intensive versus standard blood-pressure control on 1 endpoint Myocardial infarction, ACS Stroke Heart failure CV death mmhg (goal <120 mmhg) Effects of intensive versus standard blood-pressure control on mortality Effects of intensive versus standard blood-pressure control on clinical events Effects of intensive blood pressure lowering vs ACCORD Effects of intensive blood pressure lowering on cardiovascular events Metaanalysis Perkovic V, Rodgers A: Xie X et al: Lancet

5 2003 Vorderwandinfarkt 3-Gefässerkrankung 3-fach AC-Bypass (Venen) Angina pectoris CCS III MRI: Ischämie Pos. Ergometrie Normale LV-EF Aspirin cardio 100mg Brilique 90mg Beloc ZOK 50mg ExforgeHCT 160/10/25mg Physiotens 0,2mg Crestor 40 mg Ezetrol 10mg Total Cholesterin HDL LDL Triglyzeride 7.5 mmol/l 0.88 mmol/l 5.7 mmol/l 2.02 mmol/l Wie weiter? 21-jährig 19-jährig 18-jährig Wie häufig ist die familiäre Hypercholesterinämie in der Schweiz? lial hypercholesterolaemia in patients with acute coro 1. 1: : : : Nanchen D et al: Eur Heart J

Estimated probability of event Werteachse Placebo-corrected change (%) 17.11.

2008-76% Effects of PCSK9 Antibodies on Lipids in Patients with Familial Hypercholesterolemia 15 10 5 0-5 -10-15 -20-25 -30-35 -40-45 -50-55 -60-65 -59-61 -58-51 9 9 8 7-20 -12-16 -11-32

2 mmol/l Post-hoc Adjudicated Cardiovascular TEAEs (Same as primary endpoint of ongoing ODYSSEY OUTCOMES trial ) Kaplan-Meier Estimates for Time to First Adjudicated Major CV Event Safety

03 Placebo + max-tolerated statin ± other LLT Alirocumab + max-tolerated statin ± other LLT Cox model analysis: HR=0.46 (95% CI: 0.26 to 0.82) Nominal p-value = <0.

6 Estimated probability of event Werteachse Placebo-corrected change (%) Kriterien für klinische Diagnose der HeFH (LDLR-Defekt) Dutch Lipid Clinic Network e Risk of Heterozygous Familial Hypercholesterolemia Patients Accordi Versmissen J et al: BMJ % Effects of PCSK9 Antibodies on Lipids in Patients with Familial Hypercholesterolemia Evolucomab Q2W (RUTHERFORD) Evolucomab QM (RUTHERFORD) Alirocumab (ODYSSEY-FH I) Alirocumab (ODYSSEY-FH II) LDL HDL TG LPa Baseline LDL mmol/l Post-hoc Adjudicated Cardiovascular TEAEs (Same as primary endpoint of ongoing ODYSSEY OUTCOMES trial ) Kaplan-Meier Estimates for Time to First Adjudicated Major CV Event Safety Analysis (at least 52 weeks for all patients continuing treatment, including 607 patients who completed W78 visit) Effects of Evolocumab on Cardiovascular Events OSLER Placebo + max-tolerated statin ± other LLT Alirocumab + max-tolerated statin ± other LLT Cox model analysis: HR=0.46 (95% CI: 0.26 to 0.82) Nominal p-value = <0.01 Mean treatment duration: 65 weeks No. at Risk Weeks Placebo Alirocumab Primary endpoint for the ODYSSEY OUTCOMES trial: CHD death, Non-fatal MI, Fatal and non-fatal ischemic stroke, Unstable angina requiring hospitalisation. LLT, lipid-lowering therapy 6

7 Zugelassen in USA und EU Take Home Messages USA: $ /Jahr UK: $ 6 800/Jahr USA: $ /Jahr Bei therapieresistenter Hypertonie Spironolacton versuchen Amilorid antgonisiert die diabetogene Wirkung von Hydrocholorothiazid (Rolle von K?) Bei Patienten mit erhöhtem kardiovaskulären Risiko aggressivere Blutdrucksenkung (<120 mmhg) ist besser als normale Behandlung (<140mmHg) Familiäre Hypercholesterinämie ist häufig (1:250) Kaskaden-Screening! Behandlung mit Statin PCSK9-Hemmer sind potent und vielversprechend 7

PCSK9 inhibition across a wide spectrum of patients: One size fits all?

PCSK9 inhibition across a wide spectrum of patients: One size fits all? PACE ESC Barcelona 2017 G.K. Hovingh MD PhD MBA dept of vascular medicine Academic Medical Center the Netherlands g.k.hovingh@amc.uva.nl