Upload
others
View
4
Download
0
Embed Size (px)
Citation preview
Yves Allemann
Cardiologie Pré-Vert
1630 Bulle
Roman Brenner
Kardiologie Kantonsspital
St.Gallen
Therapy of Hypertension in Patients With
Coronary Heart Disease
EUROASPIRE
Koronariker mit unkontrolliertem BD (>140/90 resp 130/80mmHg)
0%
20%
40%
60%
80%
100%
Euroaspire I Euroaspire II Euroaspire III
1995-1996 1999-2000 2006-2007
SWISSHYPE 2009
0%
5%
10%
15%
20%
KHK St. n. MI AP Revask
Hypertoniker mit KHK in Hausarztpraxen
KHK
Keine AP/Ischämie
St. n. Infarkt OHNE LV
DysfunktionArrhythmien
Angina pectoris / Ischämie
Herzinsuffizienz (LVEF )
Relevante Koronarstenose
Maeder, Praxis 2009
INFARKT
HERZINSUFF
ESH Guidelines 2013: BBl bei KHK prominent
Essenzielle Hypertonie - SHG
Antianginosa
• Negativ inotrop, negativ chronotrop
• Diastolische Füllungszeit der Koronarien wird verlängert (HF nimmt ab)
Antianginosa
• Vasodilatation (koronar, peripher)
• NDHP: Negativ chronotrop, inotrop
CCB bei Ischämie
• Indikation– Wenn BBl kontraindiziert, nicht tolerabel oder ungenügend
wirksam (AHA IIa B)
• Vorsicht– In Kombi mit BBl: lang wirksame DHP zu bevorzugen vor
NDHP (Bradykardie!)– Keine NDHP bei HF oder LV Dysfunkt.– Keine kurzwirksamen DHP (reflektorische Aktivierung des
Sympathikus und Zunahme der Ischämie)
Fall 1, Mann 68y
• KHK-2, St. n. PCI RCx vor 5 Jahren (AP)
• Kein DM
• 161/92mmHg, HF 55/min, beschwerdefrei
• Echo: LVEF 60%, keine Wandbewegungsstörungen
• ASS, Statin, Concor 5mg
Was machen Sie?• +Perindopril
• +Kombination ACE-I / Thiazid
• Betablocker erhöhen, ACE-I zusätzlich
• +Kombination CCB / ACE-I
ACCOMPLISH Studie (2008)• Population
– 11506 Pt mit aHT und hohem cv Risiko– Mittl. BD 145/80mmHg, 60% DM, 73% Dyslip.– 23% früherer MI, 36% koronare Revask, 13% stroke– 47% Betablocker, 65% Tc-Aggreg.hemmer
• Intervention– Randomisiert Benazepril-HCT vs Benazepril-Amlo
• Resultat– Prim. Endpunkt: cv Ereignis und
Cv Tod
– Früzeitiger Studienstop wegen Über-legenheit
HR 0.8 (0.72-0.9)
PROGNOSTISCHE Indikationen RAS-I +/- Infarkt ohne LV-Dysfunktion
ESC SIHD 2013 It is recommended to use ACE inhibitors (or ARBs) if presence of other conditions (e.g. heart failure, hypertension or diabetes) [HOPE, EUROPA] (IA)
ESC NSTEMI 2015 ACE inhibitors are recommended in patients with systolic LV dysfunction or heart failure, hypertension or diabetes (agents and doses of proven efficacy should be employed). ARBs are indicated in patients who are intolerant of ACE inhibitors [HOPE, ONTARGET, EUROPA]
ESC STEMI 2012 ACE inhibitors should be considered in all patients in the absence of contraindications [HOPE, EUROPA]. (IIa A)
Use of ACE inhibitors should be considered in all patients with atherosclerosis, but, given their relatively modest effect, their long-term use cannot be considered mandatory in post-STEMI patients who are normotensive, without heart failure, or have neither LV systolic dysfunction nor diabetes.
AHA / ACC SIHD ACE inhibitors should be prescribed in all patients with SIHD who also have hypertension, diabetes mellitus, LVEF 40% or less, or CKD, unless contraindicated [HOPE, EUROPA] (I A).
AHA / ACC STEMI 2004 An ACE inhibitor should be prescribed at discharge for all patients without contraindications after STEMI. (I A)
An ACE inhibitor should be administered orally during convalescence from STEMI in patients who tolerate this class of medication, and it should be continued over the long term. (I A)
Drug-drug comparison: CCB bei stabiler KHK
• INVEST: – 22576 Pt mit stabler KHK und HT. – Verapamil vs Atenolol. – Kein Unterschied prim Endpunkt (Tod + MACE)
• ALLHAT bei KHK: – Pt mit KHK aus ALLHAT– Amlo vs Lisinopril weniger stroke, weniger Sterblichkeit (p=0.06)
• CAMELOT: – Pat mit KHK– Amlo vs Enalapril– weniger cv events bei Amlo
• VALUE: – 46% KHK– Amlo vs Valsartan prim Endpunkt=, weniger MI und stroke unter Amlo
• Kein Mortalitätsunterschied verglichen mit Kontrollen (Antihypertensiva und Placebo)
• Signifikant weniger stroke, v.a. Amlo
Fall2: Mann, aktiv, 73y • St. n. inferiorem Infarkt vor 2 Jahren, RCA-Intervention• Arterielle Hypertonie seit 12 Jahren, unter Lisinopril, später
Lisinopril HCT• Echo: LVEF 50%, inferolaterale Hypokinesie• Beschwerdefrei, keine AP, BD 132/81mmHg• möchte Betablocker wieder absetzen wegen
Leistungsminderung und Impotenz• Medikamente
– Lisinopril HCT 20/12.5 1-0-0; Concor 5 1-0-0; ASS; Atorva 40mg
• Was machen Sie?– Betablocker ausschleichen und absetzen, ev. Ersatz durch CCB
bei BD >140/90mmHg– Betablocker weiterhin indiziert. Zieldosis essenziell. Zum
Urologen schicken.– Betablocker belassen, Dosis reduzieren. HCT absetzen. CCB
wenn BD >140/90
• Was würden Sie machen, wenn der Patient ein NSTEMI gehabt hätte?
PROGNOSTISCHE Indikationen BBl nach Infarkt ohne LV-Dysfunktion
AHA / ACC SIHD 2012 IB: Beta-blocker therapy should be started and continued for 3 years in all patients with normal LV function after MI or ACS [1-3].
Iib C: Beta blockers may be considered as chronic therapy for all other patients with coronary or other vascular disease.
AHA / ACC STEMI 2004
IA: All patients after STEMI except those at low risk (normal or near-normal ventricular function, successful reperfusion, and absence of significant ventricular arrhythmias) and those with contraindications should receive beta-blocker therapy. Treatment should begin within a few days of the event, if not initiated acutely, and continue indefinitely.
Iia A: It is reasonable to prescribe beta-blockers to low-risk patients after STEMI who have no contraindications to that class of medications [6].
AHA / ACC STEMI Update 2007
IA: It is beneficial to start and continue beta-blocker therapy indefinitely in allpatients who have had MI, acute coronary syndrome, or LV dysfunction with or without HF symptoms, unless contraindicated (I A).
AHA /ACC NSTEMI 2007
IB: Patients after non low-risk NSTEMI. Continued indefinitelyIIaB: Patients after low-risk NSTEMI (normal LVEF, revascularized, no high-risk features)
PROGNOSTISCHE Indikationen BBlnach Infarkt ohne LV-Dysfunktion
ESC SIHD 2013 No recommendation for event prevention
ESC STEMI 2012 Iia B: Oral treatment with beta-blockers should be considered during hospital stay and continued thereafter in all STEMI patients without contraindications [3, 4].
The benefit of long-term treatment with beta-blockers after STEMI is well established, although mostly from trials pre-dating the advent of modern reperfusion therapy and pharmacotherapy.
ESC NSTEMI 2015 No recommendation. Betablocker therapy has not been investigated in contemporary RCTs in patients after NSTE-ACS and no reduced LV function or heart failure. In a large-scale observational propensity-matched study in patients with known prior MI, beta-blocker use was NOT associated with a lower risk of CV events or mortality [5].
[3]: Freemantle et al: Beta Blockade after myocardial infarction: systematic review and meta regression analysis. BMJ. 1999;318:1730 –7[4]: COMMIT
COMMIT Studie [4]• Population
– 45852 Patienten mit STEMI– Patienten mit geplanter PCI wurden ausgeschlossen – 50% lysiert. Mittl. SBP 128mmHg
• Intervention – randomisiert Metoprolol (bis 15mg iv, dann 200mg po) vs Placebo
• FU-Zeit – bis Spitalentlassung (max. 4 Wochen)
• Outcome: – Prim. EP: Tod, Reinfarkt oder cardiac arrest: kein Unterschied– -0.5% weniger Reinfarkte (p<0.001), -0.5% weniger VF (p<0.001), +1.1%
kardiogener Schock (p<0.00001)
Ozasa, J-CYPHER Register • Population
– 910 STEMI Patienten nach PCI
• Intervention– Gruppiert nach BBl ja (n=349)/nein bei Austritt
• FU-Zeit– 3 Jahre
Propensity score matching:Adjustierte HR: 1.1 (0.6-1.9)
Propensity score matching:Adjustierte HR: 1.1 (0.8-1.7)
Goldberger, OBTAIN-Register• Population
– 7057 Patienten mit AMI (60% NSTEMI)
• Intervention– Gruppierung der Betablocker-Dosis (% der Zieldosierung) bei Spitalentlassung
• FU-Zeit– Median 2.1 Jahre
• Outcome– Mortalität
n.s.
Absence of a special effect of BBL in theabsence of a recent infarct
Law, BMJ 2009
European Society of Hypertension (ESH) / European
Society of Cardiology (ESC)
2007 Guidelines for the Management of Arterial Hypertension
J Hypertens 2007, 25:1105-
Target BP should be at least <130/80 mmHg in:
• Diabetics
and in high or very high risk patients, such as those with associated
clinical conditions:
• Stroke
• Myocardial infarction
• Renal dysfunction / proteinuria
Reappraisal of European Guidelines on Hypertension Management
Journal of Hypertension 2009
The recommendation of previous guidelines to aim at a lower goal SBP
(<130 mmHg) in diabetic patients and in patients at very high CV risk
(previous cardiovascular events) may be wise, but it is not consistently
supported by trial evidence.
… and trials in which SBP was lowered to <130 mmHg in
patients with previous cardiovascular events have given controversial
results.
On the basis of current data, it may be prudent to recommend lowering
SBP/DBP to values within the range 130-139 / 80-85 mmHg, and possibly
close to lower values in this range, in all hypertensive patients.
2013 ESH/ESC Guidelines for the management of arterial hypertension
Blood Pressure Goals
Journal of Hypertension 2013, 31:1925–1938
2013 ESH/ESC Guidelines for the management of arterial hypertension
Blood Pressure Goals
Journal of Hypertension 2013, 31:1925–1938
2013 ESH/ESC Guidelines for the management of arterial hypertension
Blood Pressure Goals
Journal of Hypertension 2013, 31:1925–1938
… on the contrary, a number of the correlative analyses raising
suspicion about the existence of a J-curve relationship between
achieved BP and CV outcomes included a high proportion of CHD
patients and it is not unreasonable that, if a J-curve occurs, it may
occur particularly in patients with obstructive coronary disease.
Fallbeispiel
Frau, 71 Jahre
Guter Allgemeinzustand, BMI 27.1
Langjährige art. Hypertonie und bekannte KHK.
Therapie: ACE-Hemmer, Thiazid, Betablocker,
Statin, Aspirin
Symptome: Zunehmende Müdigkeit und Schwindel im Verlauf
des Nachmittags manchmal auch von «Druck auf der Brust»
begleitet.
Praxis BD im Durchschnitt : 168/68 mmHg
Blood Pressure Patterns in the General Population
30-39 40-49 50-59 60-69 70-79 > 80
70
80
110
130
150
Age
DBP
SBP
30-39 40-49 50-59 60-69 70-79 > 80
70
80
110
130
150
Age
DBP
SBP
Adapted from: Third National Health and Nutrition Examination Survey, Hypertension 1995;25:305-313
Men Women
Burt V L et al. Hypertension 1995;25:305-
150
110
70
30-39 50-59 70-79
Systolic BP
Diastolic BP
[mm Hg]
Age [years]
PP = SBP-DBP
Estimation of Arterial Stiffness: Pulse Pressure
Franklin et al., Circulation 1999; 100:354-
Pulse Pressure and CV Risk
3
2
1
CHD Hazard ratio
Pulse pressure (PP)
40 60 80 100
Fallbeispiel
Frau, 71 Jahre
Guter Allgemeinzustand, BMI 27.1
Langjährige art. Hypertonie und bekannte KHK.
Therapie: ACE-Hemmer, Thiazid, Betablocker,
Statin, Aspirin
Symptome: Zunehmende Müdigkeit und Schwindel im Verlauf
des Nachmittags manchmal auch von «Druck auf der Brust»
begleitet.
Praxis BD im Durchschnitt : 168/68 mmHg
Que faites vous?
Augmentation du ttt antihypertenseur?
(168/68 mmHg)
MAPA?
ECG?
Test d‘effort?
Echocardiographie?
Coronarographie?
Off
ice
BP
176/8
2
mmHg
180
150
120
90
60
30
12h 15h 18h 21h 00h 03h 06h 09h
Ambulatory BP
Average 24 hr: 132/78 mmHg
ECG
Fallbeispiel
Fallbeispiel
Coronary Perfusion Pressure:
Epicardial coronary artery stenosis
LV Hypertrophy / Diastolic dysfunction
Myocardial
Ischemia
LV Diastolic
Dysfunction
Left Ventricular
End Diastolic
Pressure
Coronary
Pressure
Gradient
Incidence of MI and Stroke Stratified by Diastolic BP in INVEST
Messerli FH, Ann Intern Med. 2006;144:884-
Incidence of Myocardial Infarction (%)
Incidence of Stroke (%)
Diastolic BP
[mmHg]
What is the Optimal Blood Pressure
in Patients After Acute Coronary Syndromes?[PROVE IT-TIMI 22 Trial]
Bangalore S, Circulation 2010;122;2142-
*Composite: death, MI, unstable angina, stroke ,
revascularization after 30 days
Incid
en
ce
of
Ou
tco
me
* (%
) Nadir: 85 mmHg
Treating to New Targets
Blood Pressure and Non-Fatal Myocardial Infarction
Bangalore S, European Heart Journal (2010) 31, 2897-
60 70 80 90 100 110 120 130 140 150 160 170
Diastolic BP, mmHg Systolic BP, mmHg
INVEST
Analysis of clinically significant interactions of baseline covariates
and diastolic BP for the primary outcome*
Messerli FH, Ann Intern Med. 2006;144:884-
Diastolic BP, mmHg Diastolic BP, mmHg
Ha
za
rdR
ati
o
*all-cause death, nonfatal stroke and nonfatal myocardial infarction
o with revascularization
⦁ without revascularization
Fallbeispiel
Langjährige art. Hypertonie und bekannte
symptomatische KHK.
Therapie:
ACE-Hemmer
Thiazid
Betablocker
Statin
Aspirin
Antihypertensive Drugs in Hypertensive Patients With CAD
Aronow WS, JACC 2011; 57:2037–114
Drug Class Associated Clinical Condition
Betablockers Secondary prevention
Angina
Arrhythmia
ACE-Inhibitors
ARB
Secondary prevention
Systolic LV Function (<40%)
Heart failure
LV Hypertrophy
Diabetes
Verapamil
Diltiazem
Secondary prevention
Angina
Arrhythmia
Dihydropyridine CCB Angina
Persistent high BP
Aldosterone-Antagonists Systolic LV Function (<40%)
Heart failure
Diuretics Persistent high BP
Hypervolemia
Relative risk estimates of coronary heart disease events in
single drug BP difference trials according to class of drug*
*excluding CHD events in trials of β blockers in people with a history of coronary heart disease
Law MR, BMJ 2009;338:b1665
Relative risk estimates of coronary heart disease events in 46 drug comparison
trials comparing each of the five classes of BP lowering drug with any other class of
drug*
*excluding CHD events in trials of β blockers in people with a history of coronary heart disease
Law MR, BMJ 2009;338:b1665
Fallbeispiel
Ziel Blutdruck???
< 140 / 90 mmHg
< 140 / 85 mmHg
< 130 / 80 mmHg
The <140/90 mmHg BP target is reasonable for the secondary prevention
of cardiovascular events in patients with hypertension and CAD.
(Class IIa; Level of Evidence B)
Hypertension 2015
BP target <140/90 mmHg
Hypertension 2015
A lower target BP (<130/80 mmHg) may be appropriate in some individuals
with CAD, previous MI, stroke or transient ischemic attack, or CAD risk
equivalents (carotid artery disease, PAD, abdominal aortic aneurysm).
(Class IIb; Level of Evidence B)
BP target <130/80 mmHg
Take-Home Messages
In hypertensive patients with (suspected) coronary artery disease:
├ Coronary perfusion occurs in diastole
├ J-curve, particularly for diastolic BP
├ J-curve for diastolic BP is organ-specific (heart)
├ High-risk patients: elderly ± LVH ± wide pulse pressure
├ Goal BP: 140 / 90 mmHg
Goal BP: 130 / 80 mmHg (may be appropriate in some individuals with CAD)
├ Indicated drug classes are: Betablockers (Verapamil, Diltiazem), ACE-
Inhibitors or ARBs.