Lifestyle Changes

17.11.2015
Prävalenz der Hypertonie und
Hypercholesterinämie
RF-management: Guidelines
Georg Noll
HerzKlinik Hirslanden
BMJ 2005;330:1461–2
Hypertension management in England 1994 - 2011
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 2014
1
17.11.2015
Estimated Sodium Excretion and Risk
of Major Cardiovascular Events
PURE
NaCl-Ausscheidung im Urin (g/24Std)
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.
10.7
10.3
8.1
7.2
O’Donnell M et al: N Engl J Med 2014
10.6
7.8
7.6
Chappuis A et al: BAG 2011
Aged over 55 years or black
person of African or
Caribbean origin of any age
Aged under 55
years
Pharmakotherapie der arteriellen Hypertonie
Step 1
Ca++-Antagonist
RAS-Hemmer
10.5
A
C
Zielwert
Step
2
ß-Blocker
für alle
A + C<140/90 mmg
ausser:
<140/85
mmHg
A+
C+D
Step Diabetiker
3
A=ACEI or ARB
C=CCB
>80J Start ≥160 Ziel <150 mmHg
Diuretikum
D=Thiazide diuretic
Step 4
Resistant hypertension
consider further diuretic
alpha or betablocker
consider seeking expert advise
2015
Aged over 55 years or black
person of African or
Caribbean origin of any age
Aged under 55
years
Step 1
A
Prevalence of resistant hypertension
Observational studies
C
Step 2
A+C
Step 3
A+C+D
Step 4
NICE 2011
Resistant hypertension
A=ACEI or ARB
C=CCB
D=Thiazide diuretic
Randomized Trials
consider further diuretic
alpha or betablocker
consider seeking expert advise
NICE 2011
Achelrod D et al: Am J Hypertens 2015
2
17.11.2015
Effects of spironolactone on blood pressure in ASCOT
Was bei therapieresistenter Hypertonie?
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
Effects of amiloride and hydrochlorothiazide
on glucose tolerance and blood pressure
(PATHWAY-3)
These had to be an ACE inhibitor or an ARB, a CCB, and diuretic
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 over 55 years or black
person of African or
Caribbean origin of any age
Aged under 55
years
Step 1
A
C
Step
2
Zielwert
A + C<140/90 mmg
für alle
ausser:
A+
C+D
<140/85
mmHg
Step Diabetiker
3
A=ACEI or ARB
C=CCB
>80J Start ≥160 Ziel <150 mmHg
D=Thiazide diuretic
Step 4
Resistant hypertension
consider further diuretic
alpha or betablocker
consider seeking expert advise
????????
N
Age
>75 y
CKD
CVD
Framingham Risk >15%
Baseline BP (mmHg)
Statins
Aspirin
9361
67.9 y
28 %
28 %
20 %
61%
140/78
43 %
51 %
NICE 2011
3
17.11.2015
Intensive versus Standard Blood-Pressure Control
SPRINT
Effects of intensive versus standard blood-pressure
control on 1° endpoint
SPRINT
Myocardial infarction,
ACS
Stroke
Heart failure
CV death
136.2 mmHg (goal <140 mmHg)
Stopped early after 3.26 years
121.4 mmHg (goal <120 mmHg)
NEJM 2015
Effects of intensive versus standard blood-pressure
control on mortality
SPRINT
NEJM 2015
Effects of intensive versus standard blood-pressure
control on clinical events
SPRINT
NEJM 2015
Effects of intensive blood pressure lowering
SPRINT vs ACCORD
Perkovic V, Rodgers A: NEJM 2015
NEJM 2015
Effects of intensive blood pressure lowering
on cardiovascular events
Metaanalysis
Xie X et al: Lancet 2015
4
17.11.2015
F.B. 1972
F.B. 1972
2003 Vorderwandinfarkt
3-Gefässerkrankung
3-fach AC-Bypass (Venen)
Angina pectoris CCS III
MRI: Ischämie
Pos. Ergometrie
Normale LV-EF
Aspirin cardio 100mg
1-0-1
Brilique 90mg
1-0-1
Beloc ZOK 50mg
1-0-1
ExforgeHCT 160/10/25mg
1-0-0
Physiotens 0,2mg
1-0-1
Crestor 40 mg
1-0-0
Ezetrol 10mg
1-0-0
F.B. 1972
Total Cholesterin
7.5 mmol/L
HDL
0.88 mmol/L
LDL
5.7 mmol/L
Triglyzeride
2.02 mmol/L
F.B. 1972
21-jährig
19-jährig
18-jährig
Wie weiter?
Prevalence of familial hypercholesterolaemia in patients with acute coronary syndr
Wie häufig ist die familiäre Hypercholesterinämie
in der Schweiz?
1.
1:250
2.
1:500
3.
1:2’000
4.
1:10’000
Nanchen D et al: Eur Heart J 2015
5
17.11.2015
Kriterien für klinische Diagnose der HeFH (LDLR-Defekt)
Dutch Lipid Clinic Network
Effects of PCSK9 Antibodies on Lipids
in Patients with Familial Hypercholesterolemia
Werteachse
-76%
Placebo-corrected change (%)
Heart Disease Risk of Heterozygous Familial Hypercholesterolemia Patients According to Statin Treatment
15
10
5
0
-5
-10
-15
-20
-25
-30
-35
-40
-45
-50
-55
-60
-65
9
8
7
-20 -12 -16 -11
-32 -28 -18 -20
Evolucomab Q2W (RUTHERFORD)
Evolucomab QM (RUTHERFORD)
Alirocumab (ODYSSEY-FH I)
Alirocumab (ODYSSEY-FH II)
LDL
Versmissen J et al: BMJ 2008
9
-59 -61 -58 -51
HDL
TG
LPa
Baseline LDL 3.5 - 4.2 mmol/L
Effects of Evolocumab on Cardiovascular Events
OSLER
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)
Estimated probability of event
0.06
Placebo + max-tolerated statin ± other LLT
Alirocumab + max-tolerated statin ± other LLT
0.05
Mean treatment duration:
65 weeks
Cox model analysis:
HR=0.46 (95% CI: 0.26 to 0.82)
Nominal p-value = <0.01
0.04
0.03
0.02
0.01
0.00
0
12
24
36
48
60
72
84
Placebo
788
776
731
703
682
667
321
127
Alirocumab
1550
1534
1446
1393
1352
1335
642
252
No. at Risk
†Primary
39
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
Weeks
NEJM 2015
6
17.11.2015
Zugelassen in USA und EU
USA: $ 14’600/Jahr
USA: $ 14’100/Jahr
UK: $ 6’800/Jahr
Take Home Messages
• 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