3. How should hypertension
be diagnosed?
Screening BP – High?
± Diagnose Hypertension
Use Mean daytime BP to define
hypertension
Offer Ambulatory BP
Measurement (ABPM)
Days
or
weeks
CVD Risk
&
TOD
Assessment
4. 2015
Criteria for the diagnosis of hypertension
and recommendations for follow-up: overview
Measurement using electronic (oscillometric) upper arm devices is preferred over auscultation
Ambulatory Blood Pressure Measurement
Automated Office Blood Pressure
Home Blood Pressure measurement
Office Blood Pressure measurement
2015
5. 2015
Criteria for the diagnosis of hypertension
and recommendations for follow-up: summary
Measurement using electronic (oscillometric) upper arm devices is preferred over auscultation
ABPM: Ambulatory Blood Pressure Measurement
AOBP: Automated Office Blood Pressure
HBPM: Home Blood Pressure measurement
OBPM: Office Blood Pressure measurement
2015
6. Health Behaviour Management
Intervention Target
Reduce foods with
added sodium → 2000 mg /day
Weight loss BMI <25 kg/m2
Alcohol restriction < 2 drinks/day
Physical activity 30-60 minutes 4-7 days/week
Dietary patterns DASH diet
Smoking cessation Smoke free environment
Waist circumference Men <102 cm Women <88 cm
9. CV Risk factors
Role of
RAS
Cardiovascular disease as a sequence of
related pathological events
From Circulation 2006;114:2850-70.
GoalsofTherapy
10. Comparative effect of antihypertensive drugs
on central systolic pressure
Published online: Eur Heart J. 2014;doi:10.1093/eurheartj/eht565.
11. Benefits of ACE inhibition1
“The decrease in angiotensin II levels prevents a number of deleterious cardiovascular
effects, while the increase of bradykinin has cardioprotective consequences.”
1. DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors are equal: focus on ramipril and perindopril. PostgradMed. 2013;125:154-168.
2. van Vark LC, Bertrand M, Akkerhuis KM, et al. Angiotensin-converting enzyme inhibitors reduce mortality in hypertension: a meta-analysis of randomized clinical trials of renin-angiotensin-
aldosterone system inhibitors involving 158 998 patients. Eur Heart J. 2012;33(16):2088-2097.
3. Strauss MH, Hall AS. Angiotensin receptor blockers may increase risk of myocardial infarction: unraveling the ARB-MI paradox.Circulation. 2006;114(8):838-854.
“ACE inhibitors are effective agents for treating patients with hypertension, and current data
suggest that they are more effective therapeutic agents for reducing rates of morbidity and
mortality due to cardiovascular (CV) events compared with the use of angiotensin receptor
blockers.”2,3
ACE inhibition
Angiotensin II Bradykinin
Vasoconstriction
Adhesion of monocytes
SMC growth, proliferation, and migration
Increased PAI-1 and thrombogenesis
Matrix degradation
Oxygen free radical production
Endothelial dysfunction
Vasodilation
Antiadhesion of monocytes
Increased eNOS expression
Increased t-PA and fibrinolysis
Antiremodeling effect
Antioxidant effect
Preserved endothelial function
12. 90% of ACE is a tissue enzyme present in the
heart and vessel ( endothelium and smooth
muscle )
CAD up-regulates tissue ACE and alters the
balance between:
Angiotensin II
Bradykinin
which, in turn, impairs endothelial function
ACE activity and endothelial function
13. ENDOTHELIAL FUNCTION
eNOS activity
% of apoptosis
Biologic end-points:
Clinical end-points:
• Vasomotion to endothelial dependent
stimulation (Ach, Bradykinine, etc)
• von Willebrand factor
14. PERTINENT
Analysis in cultured HUVECs
P<0.05
Apoptosis
Controls CAD PERTINENT patients
baseline 1 year
Placebo
n=44
Placebo
n=44
Treated
n=43
Treated
n=43
Controls
n=45
0
10
20 P<0.01
Apoptosis
Effects of HUVEC incubation with serum from:
#P=controls vs baseline
*P=perindopril vs placebo Ceconi C et al. Cardiovasc Res. 2006
15. WHY ?
Different tissue affinity
Different effects on the bradykinine
(anti-apoptoic) angiotensin (pro-apoptoic)
Specific effects on typical apoptoic inducer:
TNF-
(ANTI) bradykinine angiotensin (PRO)
16. Normal rate
of apoptosis: 3%
Maintenance of
endothelial layer
Excess rate of apoptosis
Onset of atheroscleroticProtection against
atherosclerosis
Endothelial apoptosis and atherosclerosis
Plaque erosion and rupture
Endothelium
continuity
19. Van Vark et al., European Heart Journal, 2012
ACE Inhibitors vs ARBs: What’s the Difference?
20. Impact of renin–angiotensin system inhibitors on mortality and major
cardiovascular endpoints in hypertension: A number-needed-to-treat analysis
Jasper J. Brugts, Laura van Vark, Martijn Akkerhuis, Michel Bertrand, Kim Fox,Jean-
Jacques Mourad1, Eric Boersma
21. Step 4
Summary of
antihypertensive
drug treatment
Aged over 55 years
or black person of
African or Caribbean
family origin of any
age
Aged under
55 years
C2
A
A + C2
A + C + D
Resistant hypertension
A + C + D + consider further
diuretic3, 4 or alpha- or
beta-blocker5
Consider seeking expert advice
Step 1
Step 2
Step 3
Key
A – ACE inhibitor or low-cost
angiotensin II receptor
blocker (ARB)1
C – Calcium-channel
blocker (CCB)
D – Thiazide-like diuretic
See slide notes for details of
footnotes 1-5
2013
22. Treatment of Systolic-Diastolic Hypertension
without Other Compelling Indications
CONSIDER
• Nonadherence
• Secondary HTN
• Interfering drugs or
lifestyle
• White coat effect
Dual Combination
Triple or Quadruple
Therapy
Lifestyle modification
Thiazide
diuretic
ACEI
Long-acting
CCB
TARGET <140/90 mmHg
ARB
*Not indicated as first
line therapy over 60 y
Initial therapy
A combination of 2 first line drugs may
be considered as initial therapy if the
blood pressure is >20 mmHg systolic
or >10 mmHg diastolic above target
Beta-
blocker*
2015
24. From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the
Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
JAMA. 2013;():. doi:10.1001/jama.2013.284427
JNC VIII
25. From: 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the
Panel Members Appointed to the Eighth Joint National Committee (JNC 8)
JAMA. 2013;():. doi:10.1001/jama.2013.284427
26. Hypertension: a multifactorial entity
Patient 1 Patient 2 Patient 3
Renin-angiotensin system
Renal Retention of Excess Sodium
Sympathetic nervous system
Vasoconstriction/
27. HT treatment guidelines ESC/ESH 2013
In what hypertensive patient is an ACE inhibitor the drug of first choice?
28. 2015
Treatment of Hypertension in Patients with
Ischemic Heart Disease
• Caution should be exercised when combining a non DHP-CCB and a beta-blocker
• If abnormal systolic left ventricular function: avoid non DHP-CCB (Verapamil or
Diltiazem)
• Dual therapy with an ACEI and an ARB are not recommended in the absence of
refractory heart failure
• The combination of an ACEi and CCB is preferred
1. Beta-blocker
2. Long-acting CCB
Stable angina
ACEI are recommended for most
patients with established CAD*
ARBs are not inferior to ACEI in IHD
Short-acting
nifedipine
*Those at low risk with well controlled risk factors may not benefit from ACEI therapy
29. 2015
Strongly consider blood pressure reduction in all patients after the acute
phase of stroke or TIA.
Target BP < 140/90 mmHg
An ACEI / diuretic
combination is preferred
Stroke
TIA
Combinations of an ACEI with an ARB are not recommended
Treatment of Hypertension in Association With Stroke
Acute Stroke: Onset to 72 Hours
30. Stage B
In all patients with a recent or remote history of MI or ACS
and reduced EF, ACE inhibitors should be used to prevent
symptomatic HF and reduce mortality. In patients
intolerant of ACE inhibitors, ARBs are appropriate unless
contraindicated.
In all patients with a recent or remote history of MI or ACS
and reduced EF, evidence-based beta blockers should be
used to reduce mortality.
In all patients with a recent or remote history of MI or ACS,
statins should be used to prevent symptomatic HF and
cardiovascular events.
I IIa IIb III
I IIa IIb III
I IIa IIb III
31. Stage B (cont.)
In patients with structural cardiac abnormalities, including
LV hypertrophy, in the absence of a history of MI or ACS,
blood pressure should be controlled in accordance with
clinical practice guidelines for hypertension to prevent
symptomatic HF.
ACE inhibitors should be used in all patients with a
reduced EF to prevent symptomatic HF, even if they do
not have a history of MI.
Beta blockers should be used in all patients with a
reduced EF to prevent symptomatic HF, even if they do
not have a history of MI.
I IIa IIb III
I IIa IIb III
I IIa IIb III
32. Pharmacological Treatment for
Stage C HFrEF (cont.)
Diuretics are recommended in patients with HFrEF who
have evidence of fluid retention, unless contraindicated, to
improve symptoms.
ACE inhibitors are recommended in patients with HFrEF
and current or prior symptoms, unless contraindicated, to
reduce morbidity and mortality.
ARBs are recommended in patients with HFrEF with
current or prior symptoms who are ACE inhibitor-
intolerant, unless contraindicated, to reduce morbidity and
mortality.
I IIa IIb III
I IIa IIb III
I IIa IIb III
39. Not all ACE inhibitors are equal
A clinical view: ACE inhibitors in CHD patients
Abbreviations: ACE, angiotensin-converting enzyme; CHD, coronary heart disease;
CAMELOT, Coparison of AMlodipine versus Enalapril to Limit Occurrences of
Thrombosis; EUROPEAN, European Trial on Reduction of Cardiac Events With
Perindopril in Stable Coronary Artery Disease; HOPE, Heart Outcomes Prevention
Evaluation; PEACE, Prevention of Events with Angiotensin Converting Enzyme inhibition;
QUIET, QUinapril Ischemic Event Trial.
DiNicolantonio J, Lavie C, O’Keefe J. Not all angiotensin-converting enzyme inhibitors
are equal: focus on ramipril and perindopril. Postgrad Med. 2013;125:154-168
“Only use of the ACE inhibitor perindopril
has demonstrated clear reductions in CV
end points in patients who have been
treated in ways that are reflective of
current-day intensive practice
(ie, on optimal medical therapy and at a
lower baseline risk of CV events compared
with patients receiving ramipril in HOPE).”
46. Clinical Drug Investigation ; August 2013, Volume 33, Issue 8, pp 553-561
THE ABSOLUTE REDUCTIONS IN MEAN 24 H SBP
-22 mmHg
-11 mmHg
-12 mmHg
-15 mmHg
47. Thiazide like diuretic (low dose→HCT 12.5-25mg od)
B blocker (cardioselective)
Long acting calcium channel blockers (amlodipine)
1st ACEIs
Monotherapy
Drug therapy in
Hypertension with Diabetes
2nd ARBsOR
+
Combination
48. Hypertension :
ALLHAT, ANBP2,
UKPDS, ASCOT,
ADVANCE
Stable CAD, High-Risk Patients:
HOPE, EUROPA
After MI:
SAVE, AIRE, TRACE,
Heart Failure:
CONSENSUS,
SOLVD,
CHF-PEP
Remodeling:
PREAMI
Adapted from Dzau V, Braunwald E. Am Heart J. 1991
49.
50. Regimens based on ACE inhibition, in particular with perindopril, significantly improve survival in
patients with hypertension or High Risk of CV Disease
Overall study population
Subpopulation with diabetes
Subpopulation without diabetes
Berthet K. Blood Pressure 2004;
EUROPA Investigators. Lancet 2003;362:782-88.
Dahlof B. Lancet 2005;366:895-906.
Total CV events and procedures
-15
-10
-5
0
-20
RRR
(%)
-13%
-18%
-16%
CV death, MI, cardiac arrest
-15
-10
-5
0
-20
RRR
(%)
-20%
-19% -19%
Recurrent stroke
-30
-20
-10
0
-40
RRR
(%)
-38%
-28%-28%
51.
52. • Hypertension is a major risk factor for mortality worldwide.
• Among RAAS inhibitors, only ACE inhibitors have demonstrated a
further significant 6% mortality reduction in hypertensive patients
(P=0.007)
• No significant reduction in all-cause mortality could be
demonstrated with ARBs (HR, 0.99 (0.95-1.04), P=0.75)
• ACEI are still first choice but use ARBs in all situations where ACEI
cannot be tolerated…
• Perindopril significantly reduced all-cause mortality by 13% among
contemporary patients with arterial hypertension (P<0.001)
M. Bertrand. Oral session ESC, Paris 2013
Conclusion
