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Resistant HT
Resistant HT
Resistant HTN-definition
BP > 140/90 inspite of three concurrent
Resistant HTN-evaluation
Compliance
Analgesics, appetite suppressants,
erythropoetin
Resistant HTN-evaluation
Alchohol binge
Nasal decongestants
Cold and cough medications
Indigenous drugs
Obesity-hypoventilation
Renal parenchymal disease
Polycystic kidney
Primary aldosteronism
Resistant HTN-evaluation
Cushings disease
Pregnancy induced hypertension
Coarctation of aorta
Resistant hypertension-pseudoresistance
High office blood pressure
pressure
Mortality
16 million
7-8 million
4-3 million
2-3 million
Lewington 2002
Population
All cardiovascular
High blood pressure
High cholesterol
Overweight and obesity
Norman M Kaplan, Lionel H Opie Lancet 2006;367:168-76
Hypertension in India
Control remains suboptimal..
Kerala
One third
AWARE
Total
One fourth
TREATED
One tenth
CONTROLLED
Hypertension in India
Control remains suboptimal..
% of
uncontrolled
hypertensive
patients
Uncontrolled Hypertension
Complications..
Oxidative Stress /
Endothelial
Dysfunction
Target Organ
Damage
Tissue Injury
(IHD, Stroke)
Vascular Disease
Vascular
Dysfunction
Risk Factors:
Diabetes
Hypertension
Pathological
Remodeling
Target Organ
Dysfunction (HF, Renal)
End-stage
Organ Failure
MI: Myocardial
infarction
HF: Heart failure
Death
Adapted from Dzau et al. Circulation. 2006;114:2850-2870.
Uncontrolled Hypertension
Contributing factors..
Uncontrolled Hypertension
1. Monotherapy with drugs
BP
RAAS blockade is the foundation
of modern combination therapy
ALLHAT
shows
need for 3
drugs
when
continued
on longterm basis
Chrysant 2011
ACCOMPLISH
N ENGL J MED 359;23, DEC 2008
Uncontrolled Hypertension
%
%
% pts
ACCOMPLISH: Avoiding Cardiovascular Events through COMmbination therapy in Patients Living wIth Systolic Hypertension
Uncontrolled Hypertension
2. Concomitant risk factors ..
Uncontrolled Hypertension
2. Concomitant risk factors..
Diabetes
Diabetes
Hypertension
Hypertension
HTN vs No HTN
2.4x in DM
DM vs No DM
2.0x in HTN
Resistant Hypertension
Intensive
Standard
HbA1c goal
<6%
<7.5%
Systolic BP
<120
<130
ACCORD
% pts
Resistant Hypertension
patient adherence
%
%
Resistant Hypertension
Edema
Edema
1.83
1.64
-blockers
1.23
CCBs
1.08
ACE-Is
1.00
ARBs
0.92
0.5
1.0
2.0
CCB + ARB:
The Synergies of Counter-Regulation (1)
CCB
Arteriodilation
Peripheral oedema
Effective in low-renin patients
Reduces cardiac ischaemia
BP
Synergistic
BP reduction
Complementary
clinical benefits
29
CCB
RAS activation
No renal or CHF
benefits
CCB + ARB:
The Synergies of Counter-Regulation (2)
CCB
Arteriodilation
Peripheral oedema
Effective in low-renin patients
Reduces cardiac ischaemia
ARB
Venodilation
Attenuates peripheral oedema
Effective in high-renin patients
No effect on cardiac ischaemia
30
BP
Synergistic
BP reduction
Complementary
clinical benefits
ARB
RAS blockade
CHF and renal
benefits
CCB
RAS activation
No renal or CHF
benefits
as Initial Therapy
31
(n = 31)
32
(n = 13)
Severe HTN
180 < 1902
(n = 305)
(n = 71)
1. Littlejohn et al. J Clin Hypertens. 2009;11:207213; 2. Neutel et al. J Clin Hypertens. 2010: In press; ASH 2010
poster presentation (LB-PO-10) & data on file
T80/A10
Patients (%)
A10
(n = 65)
(n = 183)
50 mmHg
(n = 37)
(n = 117)
55 mmHg
(n = 20)
60 mmHg
(n = 61)
(n = 62)
(n = 36)
(n = 100)
T80/A10
1. TEAMSTA Severe HTN study (data on file; Boehringer Ingelheim Pharmaceuticals, Inc);
2. Neutel et al. J Clin Hypertens. 2010: In press; ASH 2010 poster presentation (LB-PO-10).
Black
(n = 30)
Severe HTN
180/95 mmHg2
(n = 379)
185.4
T80/A5
T80/A10
(n = 405)
(n =379)
Baseline
80%*
147.7
137.9
37.9 mmHg
Week 2
47.5 mmHg
Week 8
24-h ABPM
36
p < 0.0001
A10
(n = 58)
T80/A10
(n = 52)
38
Patients with
AEs > 1% incidence (%)
Placebo (n = 46)
A mono (n = 319)
NasoUpper Influenza
pharyn- respiratory
gitis
tract
infection
T/A (n = 789)
Back
pain
Dizziness
Headache Peripheral
oedema
Fluid leakage
Arterial
dilation
(CCBs)
No
venous
dilation
Fluid leakage
Capillary bed
40
Opie et al. In: Opie LH, editor. Drugs for the Heart. 3rd ed. 1991:4273; White et al. Clin Pharmacol Ther.
1986;39:4348; Gustaffson. J Cardiovasc Pharmacol. 1987;10:S121S131.
* p <0.05; p <0.0001
Littlejohn TW et al. J Clin Hypertension. 2009;11(4):207-213
p < 0.0001
90%
A10
(n = 124)
T4080+A5A10
T4080+A5
(n = 264)
71%
(n = 543)
43
1. Neutel et al. J Clin Hypertens. 2010: In press; 2. White et al. Blood Press Monit. 2010: In press; 3. Littlejohn et al. J Hypertens.
2008;26(suppl 1):S494; 4. Neldam, Lang. J Clin Hypertens. 2009;11(Suppl s1):114 (P279); 5. Littlejohn et al.
J Clin Hypertens 2009:11:207213.
Resistant Hypertension
JNC - 7
< 140 / < 90 mm Hg in pts
with h/o of CVD
Resistant Hypertension
Group A
Group B
Efficacy Parameter:
1.Effect on both SBP and DBP in sitting and supine position
2.Quality of Life (QOL) questioner
3.Safety parameters
Follow-up: on week 1, 2, 4, 6, 8 and 10 for periodic efficacy and
safety evaluations.
Manish Maladkar et al.
Open Journal of Internal Medicine, 2012, 2, 67-71
Amlodipine
HCTZ
ARB
Potent vasodilator
Ca Channel blocker
Potent vasodilator
Long half-life of
24 h
Insurmountable
antagonism for 24 h
BP control
vasculoprotection
[NO]
Long half-life of
36-48 h
Excellent
antianginal agent.
vasculoprotection
[NO]
Diuretic property
Thiazide diuretic
Medium potency
diuretics acting by
inhibiting the
Na+/Clsymporter in the
DCT
Long half life of
upto 12 h
40 to 80 mg
2.5 to 5 mg
Amlodipine
HCTZ
Dose dependent
rise in side effects
Safe coprescription
profile
Counters Renin rise due
to Diuretic properties of
HCTZ & Amlodipine
Counteracts
hypokalemia of HCTZ
by preventing
aldosterone release
Potential to diminish
peripheral oedema by
providing both arterial
& venous
vasodilatation.
Lipid neutral
Peripheral edema
, incidence
doubles or triples
with dosages of 5
to 10 mg
Lipid neutral
Resistant HTN-emerging Rx
Resistant Hypertension-Summary
Resistant HTN is common
Detailed evaluation and investigation may
be required