Transcript Treatment of Hypertension by Dr Sarma

1 www.drsarma.in
Dr.Sarma@works
Welcome, Dear Friends
www.drsarma.in
Dr.Sarma@works
2
The Almighty
Pardons and Grants me heaven
Even if I don't know a single letter about
Crutz Feld Jacob’s Disease
Tsutsugamushi Fever
Criggler Nazzar Syndrome
South American equine encephalitis and
Many and much more rarer topics
BUT …….
www.drsarma.in
Dr.Sarma@works
3
The Almighty
Will drag me to hell and will not pardon
My ignorance of even the minute details of HT
My indifference to apply the current knowledge
My negligence in screening for HT, TOD
My despondency about preventing TOD
My inadequacy in maintaining my patients
as normo-tensive as possible –
(This is applicable to all common diseases)
www.drsarma.in
Dr.Sarma@works
4
Treatment of Hypertension
A CLINICAL APPROACH
Dr.Sarma RVSN, M.D., M.Sc (Canada)
Consultant Physician and Chest Specialist,
# 5, Jayanagar, Tiruvallur – 602 001
93805 21221, (044) 27660593
www.drsarma.in
5
Treatment of Hypertension
A CLINICAL APPROACH
Management of Hypertension
Based on the latest recommendations of
JNC VII, ISH, ESH, WHO
www.drsarma.in
6
Globally Renowned HT Societies
1. JNC VII – Joint National Committee on HT, USA
2. ISH – WHO International Society on HT
3. AHA – American Heart Association, USA
4. ACC – American College of Cardiologist
5. BHS – British Hypertension Society
6. NIHLB – National Inst. Heart Lung & Blood vessels
7. EHS – European Hypertension Society
8. CHS – Canadian Hypertension Society
9. NKF – National Kidney Foundation, USA
10.AKA – American Kidney Association, USA
www.drsarma.in
7
www.drsarma.in
8
WHAT IS NEW IN HYPERTENSION?
www.drsarma.in
9
HYPERTENSION
What we record as B.P.
It is only a marker of the bigger problem
The Truth is
Hypertension is a multi-organ systemic disease
The Problem is
Hypertension is asymptomatic in 85% of cases
www.drsarma.in
10
How to be wise in HT?
It is wrong
To consider Hypertension as an isolated disease
The Truth is
Hypertension, DM, Dyslipidemia, Obesity often coexist
They are the 4 pallbearers to the grave of CHD, CVD
For all of them
Primary and secondary prevention by TLC is the answer
Afflicted with one, must be screened for all other thieves
www.drsarma.in
11
Treatment Goal
Goal BP
Keep B.P. < 140/90 mm Hg in each patient
This may be revised to 120/80 may be ? 110/70
MRFIT’s cut off values are 115/75 mm Hg
The Truth is
It is essential to keep the B.P at or below the goal
But, It also matters how the goal B.P. is achieved !
www.drsarma.in
12
Definitions
As per JNC VII and ISH (WHO) 2004
1. What is normal B.P ?
2. What is pre hypertension ?
As per JNC VII and ISH (WHO) 2004
Normal SBP < 120 and DBP < 80
Pre HT SBP 120 to 139 mm Hg
DBP 80 to 99 mm Hg
www.drsarma.in
13
Definitions
1. What is stage 1 HT ?
2. What is stage 2 HT ?
www.drsarma.in
Stage 1
SBP 140 to 159
DBP 90 to 99
Stage 2
SBP 160 and more
DBP 100 and more
14
JNC VII Classification
SBP (mm Hg)
DBP (mm Hg)
< 120
< 80
120-139
80-90
Stage 1
140 – 159
90 – 99
Stage 2
160 and above
100 and above
Category
Normal
Pre – hypertension
Hypertension
15
Definitions
Are the values same for Diabetics , CKD?
No, for DM, IHD and CKD the criteria
are more stringent
The cut off values are 10 mm lower
www.drsarma.in
Stage 1
SBP 130 to 149
DBP 80 to 89
Stage 2
SBP 150 and more
DBP 90 and more
16
Hypertension Optimal Treatment (HOT) Study
Reduction in CV events
25
p=0.005 (DM)
DM
non-DM
Events/1000 pt-years
20
15
10
5
0
<90
www.drsarma.in
<85
<80
Target diastolic BP
Lancet 1998; 351: 1755–62
17
Rule of Halves
What is this rule of halves in HT ?
•
•
•
•
•
•
•
For every 800 adults in the community
400 are HT (either ↑ SBP or ↑ DBP or both)
Of them only 200 are diagnosed HT
Of them only 100 are started on treatment
Of them only 50 are on correct drug
Of them in only 25 the goal B.P. is attained
Means 25 ÷ 400 = 6% only have goal BP
www.drsarma.in
18
How many are really Dx. and Rx.ed ??
Under control (40%)
Diagnosed
HT
37%
Hypertensives
(22%)
Normotensives (78%)
63%
Under
Un Rx.
treatment
HT
(50%)
(7.5% of the total
hypertensives)
Uncontrolled
hypertension (60%)
Undiagnosed
HT
A study from Europe on 23,339 patients
www.drsarma.in
19
Global Hypertension
Control
Percentages
of Patients
whose
Hypertension is Controlled
< 140/90 mmHg
USA
Canada
27
England
6
13
France
24
< 160/95 mmHg
Finland
Spain
Australia
20.5
20
Germany Scotland
22.5
17.5
19
India
9
> 65 years
USA: JNC VI. Arch Intern Med 1997
Canada: Joffres et al. Am J Hypertens 2001
England: Colhoun et al. J Hypertens 1998
www.drsarma.in
France: Chamontin et al. Am J Hypertens
Dr.Sarma@works
1998
MarquesMarques-Vidal P et al. J Hum Hypertens 1997
Adapted from G. Mancia / L.
Ruilope 20
Isolated Systolic Hypertension
1. What is ISH ? –
2. What percentage of 65+ aged have ISH ?
3. Which is more harmful – ↑ SBP or DBP ?
4. Why is ISH important ?
www.drsarma.in
21
Relative prevalence of SBP and DBP
40 + yrs
ISH
S&DHT
DHT
Normal
www.drsarma.in
22
R R for CVD - SBP and DBP
www.drsarma.in
23
ISH is universal after 65+
Persons who are normo-tensive at age 55
have a 90% lifetime risk for developing HTN.
www.drsarma.in
24
HT- RR of stroke and MI
20
5 Year Risk (%)
Normotensives
Hypertensives
15
10
Stroke
Myocardial
Infarction
5
0
0
20
40
60
80
100
120
140
160
180
200
220
240
260
280
300
Systolic Blood Pressure (mmHg)
www.drsarma.in
Brown, M.J. Lancet 2000; 355: 659 - 660
25
Is SBP more dangerous or DBP ?
www.drsarma.in
26
Isolated Systolic Hypertension
1. What is ISH ? –
SBP 140+ , DBP < 90
2. What percentage of 65+ aged have ISH ?
More than 90%
3. Which is more harmful – ↑ SBP or DBP ?
Of course ↑ SBP
4. Why is ISH important ?
Because of ↑↑ CVA and CHD mortality
www.drsarma.in
27
For adequate control of B.P.
Do you think we can control most of the
patients of hypertension with –
One drug
Two drugs
Three drugs
Can’t control
In most of the patients of hypertension
Two drugs are required for adequate control
More so if the initial BP is 20/10 above the goal
www.drsarma.in
28
TODAY’S PARADIGM
Gone are the days of monotherapy
It is the era of combination therapy
Why is it so?
www.drsarma.in
29
CVD Risk Factors
What are the so called CHD risk factors ?
What are known as CHD risk equivalents ?
What is Framingham risk score ?
www.drsarma.in
30
Global Risk Profile and HT
25)
www.drsarma.in
Dr.Sarma@works
31
HT combined with other CHD RF
Framingham offspring study, subjects aged 17 – 84
www.drsarma.in
32
CVD Risk Factors
What are the so called CHD risk factors ?
List discussed in previous slide
What are known as CHD risk equivalents ?
DM, PVD, CVA, Nephropathy, Retinopathy
What is Framingham 10 CHD risk estimate ?
10 year CHD risk estimate based on age,
sex, smoking, TC, HDL, SBP, Rx. for HT
see the program
www.drsarma.in
33
Target Organ Damage
Why is there TOD in HT ?
What are the organs targeted for damage ?
What is the basis of TOD ?
What tests we need to do to assess HT ?
www.drsarma.in
34
Diseases Attributable to Hypertension
Coronary heart disease
Stroke
Heart failure
Cerebral hemorrhage
Myocardial infarction
Left ventricular
hypertrophy
Hypertension
Aortic aneurysm
Retinopathy
Peripheral vascular disease
www.drsarma.in
Adapted from: Arch Intern Med 1996; 156:1926-1935.
Chronic kidney failure
Hypertensive
encephalopathy
All
Vascular
35
Target Organ Damage (TOD)
• Heart
Left ventricular hypertrophy (LVH)
Angina or prior myocardial infarction (CHD)
Prior Coronary revascularization PTCA or CABG
Heart failure (Systolic / Diastolic dysfunction)
• Brain
CVA Stroke or Transient Ischemic Attack (TIA)
• Kidney : Chronic kidney disease and CRF
• Vessels : Peripheral arterial disease PVD
• Eyes : Hypertensive Retinopathy
www.drsarma.in
36
Atherosclerosis – Time line
www.drsarma.in
Dr.Sarma@works
37
Endothelial NO Balance
NO
www.drsarma.in
38
Target Organ Damage - Assessment
Routine Tests
• Electrocardiogram, Echocardiography (desirable)
• Urinalysis for proteinuria, Microalbuminuria
• Blood glucose (F and PP), and Hematocrit
• Serum Na and K, Creatinine or GFR, Calcium
• Lipid Profile complete, Eye examination, ABI
Optional tests
• X-Ray Chest PA
• 24 hr. urine albumin excretion or ACR
• More extensive testing is not generally indicated
www.drsarma.in
39
Target Organ Damage
Why is there TOD in HT ?
It is a disease of blood vessels.
What are the organs targeted for damage ?
Heart, brain, kidney, eye, peripheral vessel
What is the basis of TOD ?
ED, Arterial stiffness and Atherosclerosis
What tests we need to do to assess TOD ?
List discussed
www.drsarma.in
40
Paradigm Shift in HT Therapy
It is not just ↓B.P.
TODAY we must strive to
1. Alter the modifiable risk factors
2. Keep the SBP < 140 and DBP < 90
3. Prevent or halt or reduce TOD –
• LVH, CHD, CHF, CVA, CRF, PVD & Retino.
4. Prevent or control DM (as HT + DM is hazardous)
5. Prevent or control Dyslipidemia (Endothelial Dysf.)
6. Reduce morbidity and mortality
7. Improve QUALY – Quality Adjusted Life Years
www.drsarma.in
41
Target Organ Damage
What is single most imp. predictor of CHD, HF, Death ?
What time course of HT to LVH to LVF to death ?
Can LVH be regressed at all ?
Will drugs help to regress LVH and ↓TOD ?
How important is Micro-albuminuria ?
www.drsarma.in
42
Normal weight 350 to 450 g
www.drsarma.in
43
Transverse Section of HEART - LVH
10 mm
www.drsarma.in
Dr.Sarma@works
25 mm
44
Echocardiography of Heart - LVH
www.drsarma.in
Dr.Sarma@works
45
ECG and Left Ventricular Hypertrophy
www.drsarma.in
46
Chest PA view of Heart - LVH
C/T ratio > 50%
www.drsarma.in
47
Progression of HT to LVH to HF
www.drsarma.in
48
Survival Rate HT + LVH v/s NT + LVH
Source : Am Hear J, 2000; 140 (6) : 848-856.
1.00
0.99
Nomotensive-No LVH
Portion Surviving
0.98
0.97
Hypertensive-No LVH
0.96
Normotensive-LVH
0.95
Hypertensive-LVH
0.94
0.93
0
www.drsarma.in
2
4
6
8
10
12
Survival Time (Years)
14
16
18
49
Can LVH be reduced at all ??
0
-10
-20
-30
-40
-50
-60
-70
-80
-90
D
A
B
C
A+D
LVH is the Single Most important predictor
www.drsarma.in
50
Will Treatment Help ??
0
-10
-20
-30
-40
-50
-60
CHF
CVA
LVH
CVD
CHD
Combined results of 17 RCTs ( n = 48,000)
www.drsarma.in
Hebert 1993, Moser 1996
51
Value of excellent vs. good blood pressure control in NIDDM
(144/82 vs. 154/87mmHg)
Patients With Events (%)
40
Less tight control
Tight control
30
20
10
0
0
9
1
2
3
4
5
6
Years From Randomisation
7
8
Reduction in risk with tight control 32% (95% CI 6% to 51%) (P=0.019)
UKPDS, BMJ 1998;317:703-713.
MAU as a Predictor of Morbidity and Mortality
Retinopathy
LVH
All-cause
mortality
Diabetes
+
MAU
Nephropathy
Non-fatal
cardiovascular
disease
Peripheral/autonom
ic neuropathy
Parving HH. J Hypertens 1996;14 Suppl 2:S89-S94.
www.drsarma.in
53
Definitions of abnormalities in albuminuria
Category
24 hour
collection
(mg/24h)
Timed collection
(g/min)
Spot collection
(g/mg Cr)
Normal
< 30
< 20
< 30
Microalbuminuria
30-299
20-199
30-299
Clinical (macro)
albuminuria
 300
 200
 300
Because of variability in urinary albumin excretion, 2 of 3 specimens over
3-6 mon should be abnormal before considering diagnostic threshold positive
False positive: exercise < 24 hours, fever, CHF, marked hyperglycemia,
marked HTN, pyuria and hematuria.
www.drsarma.in
54
Relative Importance of MAU
10.02
10
8
6.52
6
CHD Odds
Ratio
4
3.20
2.32
2
0
Microalbuminuria
Smoking
Hypertension
Cholesterol
Eastman RC, Keen H. Lancet 1997;350 Suppl 1:29-32.
www.drsarma.in
55
Target Organ Damage
What is single most imp. predictor of CHD, HF, Death ?
LVH – LV mass index
What is the time course of HT to LVH to LVF to death ?
The chart is explained
Can LVH be regressed at all ?
Very much Yes. Diuretics and ACEi are the best
Will drugs help to regress ↓TOD ?
Yes. All TOD regresses; LVF and CVA most
How important is Micro-albuminuria ?
The most important prognostic indicator of TOD
www.drsarma.in
56
Clinical Signs of LV Dysfunction
Hypotension
Pulsus alternans
Trigeminy, Bigeminy
Reduced volume of carotid
LV apical
Enlargement/displacement
Sustained heave of apex –
Change in heart sounds
www.drsarma.in
Soft S1
Paradoxically split S2
S3 gallop
S4 impaired LV compliance)
Mitral regurgitation
Pulmonary congestion rales
57
Ankle-Brachial Index
Resting and post exercise SBP in ankle and arm.
1. Normal ABI > 1 (Ankle BP more than the arm BP)
2. ABI < 0.9 has 95% sensitivity for angiographic PVD
3. ABI of 0.5- 0.84 correlates with claudication
4. ABI < 0.5 indicates advanced ischemia
www.drsarma.in
58
Dippers & Non Dippers
What is this pattern in HT – Dippers and Non-dippers ?
What is its significance and clinical relevance ?
www.drsarma.in
59
Dippers & Non Dippers
Systolic Blood Pressure
Systolic Blood Pressure (mm Hg)
160
150
140
Non - dippers
130
Dippers
120
110
6
8
10
12
14
16
18
20
22
24
2
4
24 hours clock time
www.drsarma.in
Yonsei, Med J, Vol 43, No 3: 2002
60
Dippers & Non Dippers
Diastolic Blood Pressure (mm Hg)
Diastolic Blood Pressure
100
90
Non - dippers
80
Dippers
70
6
8
10
12
14
16
18
20
22
24
2
4
24 hours clock time
www.drsarma.in
Yonsei, Med J, Vol 43, No 3: 2002
61
Dippers & Non Dippers
1. Less than 10% circadian variation in SBP and DBP
2. Essential hypertension patients are – usually ‘Dippers’
3. Non dippers are Dx. by ABPM – They are usually
1.
2.
3.
4.
5.
6.
www.drsarma.in
Secondary HT cases
More end organ damage
More LVH
More responsive to salt restriction
Diabetics are non dippers
Diuretics convert a non dipper to dipper
62
Ambulatory Blood Pressure Monitoring - ABPM
1.
2.
3.
4.
24 hour B.P monitoring (every 15 minutes)
Today - 24 hour B.P. control is essential
Identifies dippers and non-dippers
Excludes white coat hypertension
63
Pulse wave velocity – Arterial Stiffness
Systole
Diastole
PulseTrace PCA
Sphygmocor
www.drsarma.in
64
What is MOST essential ??
 Not that ‘my drug is superior to yours’
 Not that ‘this trial is better than that’
 Nor ‘this combination is better than that’
 But to get AS MANY PEOPLE as we
can to goal SBP < 140 & DBP < 90
 And prevent or halt TOD.
 Of course, tailor the treatment as per
individual patient’s co-morbidities.
www.drsarma.in
65
Morbidity and Mortality in HT
Most of the morbidity and mortality of HT is due to
 LVH – LV diastolic and systolic dysfunction
 Increased risk of Coronary Artery Disease
 Increased risk of Cerebral Vascular Disease
 Hypertensive heart failure
 Chronic Renal Disease of hypertension
 Hypertensive vascular damage
www.drsarma.in
66
The correct Approach to HT
• Are all patients screened for hypertension?
Step1 • Are all hypertensives correctly identified?
• Are they evaluated for co-morbidities/TOD?
Step 2 • Are they assessed for CHD risk factors?
• Are the correct drug combinations prescribed?
Step 3 • What is the compliance for medicines & f/u?
• Is the goal B.P. achieved and maintained?
Step 4 • Are there any complications/ side effects?
www.drsarma.in
67
So, What is new in Hypertension ?
1. High B.P recorded is only a clinical marker disease
2. HT is a multi-organ disease, often asymptomatic
3. Not to consider in isolation- Must look for ‘Co-Thieves’
4. Today’s goal BP is 140/90 – It will sure be less tomorrow
5. It matters to attain goal; matters more how it is attained
6. In DM, CKD, IHD the cut off values are 10 mm less
7. Remember rule of ½ in HT– Adequate control only in 7%
www.drsarma.in
68
What is new in Hypertension - continued
8. ↑ SBP is more important than ↑ DBP; Often ignored it is !
9. Wide pulse pressure (SBP-DBP) signifies arterial damage
10. Day’s of monotherapy have gone; Combined Rx replaces
11. All HT must be screened for CHD risk factors & addressed
12. Target organ damage (TOD) must be investigated and Rx.
13. LVH is the single most predictor of mortality and morbidity
14. ABI, MAU, ABPM, PWV etc., identify high risk cases early
www.drsarma.in
69
70www.drsarma.in
Dr.Sarma@works
Lifestyle Modification
1. Life style modification is the sheet anchor
in the management Hypertension.
2. This surely reduces the number of drugs
used and their dosage in controlling HT.
3. Any drug treatment has value only when
coupled with Life style modification.
www.drsarma.in
71
www.drsarma.in
Dr.Sarma@works
72
Lifestyle Modification
Modification
Weight reduction
Approximate BP reduction
(range)
5–20 mm/10 kg wt loss
Adopt DASH eating plan
8–14 mmHg
Dietary sodium reduction
2–8 mmHg
Physical activity
4–9 mmHg
Abstinence from alcohol
2–4 mmHg
www.drsarma.in
All put together reduce BP by 20 to 55 mmHg
73
What to choose from the ocean
 16 different classes of drugs
 117 approved molecules as on date
 Innumerable drug combinations
Over 1800 clinicalchange
trials of repute
Nosignificant
in the
 Five international
proportion
of HTsocieties
underon HT
control
 Seven JNC guidelines so far
 Multiple target organs damage
 Many co-morbidities
 Varied outcomes of interest
www.drsarma.in
 Cost constraints
74
Many avoidable HT deaths !
On April 12, 1945, US President Franklin D. Roosevelt
died of cerebral hemorrhage, a consequence of HT. It
was a devastating illness for him.
By current standards, President Roosevelt’s death was
unnecessary. President Roosevelt was never treated
with Anti-hypertensive drugs.
Modern treatment would have controlled his BP and
prolonged his life.
Arch Int Med, Sept, 23,1996
. . . so also of many others!
www.drsarma.in
75
The Many Faces of HT Therapy Today
Enalapril
Lisinopril
Ramipril
Quinapril
Perindopril
Hypertension
www.drsarma.in
76
Which drug should we prescribe ?
 Choice must be tailored to individual
patient
 Should be rational and as per approved
guidelines
 Only class1 evidence based medications
to be used
 Suitable to patients’ purse
 Can never be arbitrary
www.drsarma.in
77
Physicians’ Bias in HT
 Isolated SHT is often dubbed as ‘aging factor’
 To consider HT is only in the ‘ARM’ and not in the body
 No concept of ‘pulse pressure’ – Not seeing the whole
 Worry about side effects – Need to watch, not to worry
 OK, some control is achieved – why attain goal BP ?
 Not insisting on compliance with drugs and assessments
 Pressure from patients – B.P. How much ? How much ?
 Concentrating on the pill and not on the ill – TLC forgotten
www.drsarma.in
78
Anti Hypertensive drug classes
The
A, B, C, D
approach
www.drsarma.in
79
Anti Hypertensive drug classes
 ACEi – Angiotensin converting enzyme
inhibitors – Enalapril- let us call them ‘A’
 ARB – Angiotensin Receptor Blockers –
Losartan - Let us call them also as ‘A’
 BB – Beta Receptor Blockers – Metoprolol,
Carveidilol, Atenelol - let us call them ‘B’
 CCB – Calcium channel blockers – Amlodepine
Verapamil, Diltiazem - let us call them ‘C’
 Diuretics – Hydrochlor Thiaz.- Furosemide,
Spiranolactone - let us call them ‘ D ’
www.drsarma.in
80
AB/CD Rule – HT Treatment
(AB/CD = ACEi, Beta-blocker
Ca++-blocker, Diuretic)
AGE
Renin
Younger (< 55)
High Renin HT
I ACEi
II
BB
A+B
Resistant HT /
Intolerance
www.drsarma.in
III
Older (> 55)
Low Renin HT
III
A+B+D
D+C+A
CCB
Diuretic I
D + C II
IV: Add / substitute alpha blocker
V: Re-consider 20 causes  trial of spironolactone
Dickerson et al. Lancet 353:2008-11;1999
81
The A B C D classes
D
A
Diuretics
ACEI, ARB
Ca
channelBlockers
ACEI
DIURETICS
and ARB
βBlockers
D A
Fourth
Choice,
Useful
Second
First
Best
Best
Choice
Choice
Goodand
third
Choice
Can
be
combined
with
D, B,
A C
B
C with
Can
Can
be
combined
with
A,
Canbe
becombined
combined
withD,
A, B,
DC
www.drsarma.in
B
C
β-Blockers
Ca-Blockers
82
A B C D – some brand names
 Thiazide diuretics –
Hydrochlorothiazide - Aquazide, Hydride, Xenia
Chlorthalidone – Hythalton, Loop diuretic – Frusemide
 Potassium sparing
Triamterene, Amiloride, Spironalactone (Aldo anta)
 Beta blockers
Selective – Metoprolol, Metoprolol XL, Atenelol
Combined alpha and beta blockers – Carveidilol, Labetolol
 ACEI – Enalapril, Ramipril, Lisinopril, Quinapril, Perindopril
 ARB – Losartan, Valsratan, Candesartan, Irbesartan
 CCB – Nefedipine, Amlodipine, Varapamil, Diltiazem
 Alpha Blokers – Prazocin, Doxizocin, Terazocin, Tamsulocin
www.drsarma.in
83
Hypertension – Why Combinations ?
 If goal BP is not achieved by a single drug in full dose
 Then adding another agent will help achieve the goal BP
 Two agents sometimes nullify each others side effects
 Fixed dose combinations will reduce the no. of tablets
 Once daily formulations are good for compliance
 Sustained release or LA formulations for 24 h BP control
 If three drugs can’t achieve goal BP – Resistant HT
www.drsarma.in
84
Drug Combinations
Dr.Sarma@works
85
Hypertension – Rational Drug Combinations
ACEI and ARB = A
Diuretics = D – Rank 1
Beta Blockers = B
ACEI and ARB = A – Rank 2
Calcium Channel (CCB) = C
Beta Blockers = B – Rank 3
Diuretics Drugs= D
CCB = C – Rank 4
D and A combination is excellent -
Ramace H, Losar H, Enace D
D and B combination next -
Betaloc H, Atecard D, Tenoric
D and C combination sixth -
Amlogaurd H, Stamlo D
A and B combination Third -
Losar A, Cardif Beta
A and C combination fourth -
Amlopres L, Hipril A, Amlo LS
B and C combination fifth -
Amlo AT, Amlobet, Beta Nicardia
www.drsarma.in
86
Some Irrational Combinations
Beta blockers + Beta1 stimulants - Rebound HT, Paradoxical BP ↑
Beta blockers + Vepapamil -
Extreme bradycardia, HB, CHF
Thiazide + Furesemide
Potential volume ↓ and K ↓
CCB + Thiazide
-
-
No RCTs to support the additive
Prazocin + Beta blocker -
They nullify the effects of each other
Verapamil / Dilzem + Nefidepine -
No rationale (cardiac actions contridic)
Beta blocker + ACEI
Not for HT alone, Good for CHF, MI, IHD
Sub clinical doses of two drugs
Try one drug in good dosage, then add
Two drugs of same class -
No rationale (like Enalapril + Ramipril)
(Atenelol + Metoprolol, Nefidepine + Amlo)
www.drsarma.in
87
DIURETIC
I am
KNOW
‘D’ for
MEDIURETIC
WELL
 My Good aspects
Fluid depletion, Na washout, Low cost
Improve CHF, Systolic function, Ca saving
Reduce LVH, Morbidity & Mortality
 My Bad aspects
Potassium washout, ↑ in Uric acid, ↑ Ca
Adverse on Lipids, Glucose control
 Don’t use me in
Gout, Hypokalaemia
Dyslipedemia, Uncontrolled DM
www.drsarma.in
88
ACEI, ARB
I am ‘A’
KNOW
for ME
ACEI
WELL
and ARB
 My Good aspects
Improve Diastolic function, Systolic function
Control Proteinuria, Very favourable in DM
Improve Coronary Ischemia, Good on Lipids
Reduce LVH, Morbidity & Mortality
 My Bad aspects
Bradykinin accumulation, Angio-edema
↑ Serum K , ↓ GFR
 Don’t use me in
Pregnancy, Creatinine is > 3 mg%, ↑ K 5.0 meq
Bilateral Renal Artery Stenosis, Angio-edema
www.drsarma.in
89
β Blocker
KNOW
MEβBlocker
WELL
I am
‘B’ for
 My Good aspects
↓Heart rate, ↓Forceof contraction, ↓Conduction
↓Myocardial O2 demand, Improve Ischemia
Improve QUALY in CHD, Useful in CHF, Migraine
 My Bad aspects
Constrict peripheral vessels, Bradycardia
Unfavourable on Lipids, Glucose
 Don’t use me in
Bradycardia, Conduction defects, Caution in CHF
Prinzmetal Angina, MSD, PVD, BA, COPD, Dys lipid
Pheochromocytoma, Chronic smokers
www.drsarma.in
90
Ca+ Blockers I am ‘C’ KNOW
for CaME
channel
WELLBlocker
 My Good aspects
Vasodilatory, Suitable in elderly, Low cost
Anti arrhythmic (Verapamil), ↑Coronary BF (Diltz)
Neutral on lipidemia, Vasospastic Angina
 My Bad aspects
Fluid retention, Impair failing heart
Adverse on Glucose control , Pedal edema ? Rx.
 Don’t use me in
Tachycardia, arrhythmias, CHF,
Uncontrolled DM, Volume overload
www.drsarma.in
91
ABCD Compare & Contrast
Parameter
Diuretic
ACEi, ARB
βblocker
Ca+ Blocker
Ischemia
No effect
Improves
Improves
Negative
LVH, LVF
Improves
Improves
Improves*
Negative
CV Mortality
Improves
Improves
Improves
Increases
Heart rate
No effect
No effect
Bradycardia
Tachycardia
Use in DM
Negative
Excellent
Negative
Negative
Lipid effects
Negative
Excellent
Negative
Neutral
Fluid & Na
Enhances
No effect
Vasoconstr.
Vasodilatory
K ex / bronchi Enhances
No effect
Bronchospa
No effect
UA / Conduct. ↑ Uric acid
No effect
↓conduction
No effect
www.drsarma.in
92
Which drug in each class
DIU
•
•
•
•
•
•
•
HCZ
Chlortha
Indapami
Furosemi
Torsemid
Spirono
Triamter
www.drsarma.in
ACEi
•
•
•
•
•
•
•
Enalapril
Ramipril
Lisinopril
Perindopr
Quinapril
Captopril
Benazopr
ARB
•
•
•
•
•
Losartan
Telmisart
Valsartan
Irbesartan
Candesart
BB
•
•
•
•
•
•
•
•
Metoprol
Carvedio
Atenelol
Labetolol
Nebivol
Bisiprol
Pindolol
Proprano
CCB
•
•
•
•
Amlodep
Nefidepin
Felodepin
Nitrendep
• Verapami
• Diltiazem
93
Persistence with hypertensive therapy
www.drsarma.in
94
Hypertension
Case specific approach
some selected case scenarios
www.drsarma.in
95
Case specific approach
Case 1
Pre Hypertension
TLC, No Drug
Yearly F/u
Case 2
Stage 1 HT
Single Drug
D or D + A
Case 3
Stage 2 HT
Two Drugs
D + A, D + B
Case 4
HT + Tachycardia
Beta blockers
Not CCB
Case 5
HT + Bradycardia
Heart Blocks BBB
CCB, ACEi
Not BB
www.drsarma.in
96
Case specific approach
Case 1
Pre Hypertension
TLC, No Drug
Yearly F/u
Case 2
Stage 1 HT
Single Drug
D or D + A
Case 3
Stage 2 HT
Two Drugs
D + A, D + B
Case 4
HT + Tachycardia
Beta blockers
Not CCB
Case 5
HT + Bradycardia
Heart Blocks BBB
CCB, ACEi
Not BB
www.drsarma.in
97
Case specific approach
Case 1
Pre Hypertension
TLC, No Drug
Yearly F/u
Case 2
Stage 1 HT
Single Drug
D or D + A
Case 3
Stage 2 HT
Two Drugs
D + A, D + B
Case 4
HT + Tachycardia
Beta blockers
Not CCB
Case 5
HT + Bradycardia
Heart Blocks BBB
CCB, ACEi
Not BB
www.drsarma.in
98
Case specific approach
Case 1
Pre Hypertension
TLC, No Drug
Yearly F/u
Case 2
Stage 1 HT
Single Drug
D or D + A
Case 3
Stage 2 HT
Two Drugs
D + A, D + B
Case 4
HT + Tachycardia
Beta blockers
Not CCB
Case 5
HT + Bradycardia
Heart Blocks BBB
CCB, ACEi
Not BB
www.drsarma.in
99
Case specific approach
Case 1
Pre Hypertension
TLC, No Drug
Yearly F/u
Case 2
Stage 1 HT
Single Drug
D or D + A
Case 3
Stage 2 HT
Two Drugs
D + A, D + B
Case 4
HT + Tachycardia
Beta blockers
Not CCB
Case 5
HT + Bradycardia
Heart Blocks BBB
CCB, ACEi
Not BB
www.drsarma.in
100
Case specific approach
Case 1
Pre Hypertension
TLC, No Drug
Yearly F/u
Case 2
Stage 1 HT
Single Drug
D or D + A
Case 3
Stage 2 HT
Two Drugs
D + A, D + B
Case 4
HT + Tachycardia
Beta blockers
Not CCB
Case 5
HT + Bradycardia
Heart Blocks BBB
CCB, ACEi
Not BB
www.drsarma.in
101
Case specific approach
Case 6
HT + CHD Risk F
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
102
Case specific approach
Case 6
HT + CHD Risk F
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
103
Case specific approach
Case 6
HT + CHD Risk F
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
104
Case specific approach
Case 6
HT + CHD Risk f
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
105
Case specific approach
Case 6
HT + CHD Risk F
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
106
Case specific approach
Case 6
HT + CHD Risk F
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
107
Case specific approach
Case 6
HT + CHD Risk F
ACEi (Perindo)
BB (Meto)
Case 7
HT + IHD (No MI)
BB + ACEi
B+A+D
Case 8
HT + MI or (RVP)
BB (Car) +
ACEi, ARB
Aldactone
Diltiazem
Case 9
HT + PZM Angina
CCB, α bloc
Not BB
ARB Losartan
ACE Ramipril
BB - Meto
ACEi + D
A+D+B
Case 10 HT + Diast. Dys
Case 11 HT + Sys Dys
www.drsarma.in
108
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
109
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
110
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
111
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
112
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
113
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
114
Case specific approach
Diu - Fru. Sp.
+ ARB / ACEi
Not CCB,
α bloc
ARB, ACEi
Not D, C
Case 14 HT + DM+ DKD
MD, HYZ, D
Not CCB,
ACEi, ARB
Case 15 HT + Dys lipidem.
ACEi, CCB
Not BB, D
Case 16 HT + BA / COPD
ACEi / ARB
Not BB
Case 12 HT + CHF
Case 13 HT + DM (No DK)
Case 17 HT + PVD / smoker CCB, ACEi, HZ
www.drsarma.in
Not BB
115
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 22 ISH
Case 23 HT + Cough
www.drsarma.in
116
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 22 ISH
Case 23 HT + Cough
www.drsarma.in
117
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 22 ISH
Case 23 HT + Cough
www.drsarma.in
118
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 22 ISH
Case 23 HT + Cough
www.drsarma.in
119
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Case 22 ISH - SBP > 140
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 23 HT + Cough
www.drsarma.in
120
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 22 ISH
Case 23 HT + Cough
www.drsarma.in
121
Case specific approach
α bloc, Tamsu
Not BB
α bloc, HZ,
ACEi /CCB
Not BB
Case 20 HT + Pregnancy
MD, HYZ, CCB
Not ACEi,
or ARB
Case 21 HT + Gout, ￪ UA
ACEi, CCB
Not D
Indap, Amlo,
Enalapril
Not BB
ACEi cough
Cough
remedy
Case 18 HT + BPH
Case 19 HT + ED
Case 22 ISH
Case 23 HT + Cough
www.drsarma.in
122
Case 24
Hypertension and cough
 Hypertensives may present with cough – watch out
1. Consider LVF as the cause of cough
2. Consider ACEI induced dry cough
3. Stop ACEI and give ARB or other agents
4. Check the composition of the cough remedy you give
5. Ephedrine, Pseudephedrine, should be avoided
6. Oral Beta agonists like Orciprenaline, Salbutamol,
Terbutaline the less used, the better.
7. Inhaled beta agonists, ICS are safe
8. Decongestants like phenyl propanolamine to be avoided
www.drsarma.in
123
Case 25
Secondary Hypertension – various causes
 Secondary HT
 Treatment
 Absolute contra
www.drsarma.in
Usually Stage 2 - HT
Secondary causes will be present
May present in young individuals
Look for secondary cause and treat
Life style interventions must
Vigorous efforts required to control HT
Often two or even 3 drugs may be required
Resistant HT may be encountered
Anti HT drugs as per secondary cause
ACEI or ARB in bilateral renal artery stenosis
124
Case 26
Secondary Hypertension in Pheochromocytoma
 Pheochromocytoma Usually Stage 2 HT, Episodic or Labile
Secondary adrenal medullay tumor
May present in young individuals
 Treatment
Surgical Ablation of the chromaffin tissue
HT needs to be controlled before surgery
Alpha blockers are the drugs of choice
Phentolamine, Phenoxybenzamine, Prazocin
Vigorous efforts required to control HT
Often two or even 3 drugs may be required
Resistant HT may be encountered
 Surgery
First reduce HT, then surgery
 Do not use
www.drsarma.in
Beta blockers
125
Case 27
 Resistant HT
 Reasons
 Rationale
www.drsarma.in
Resistant Hypertension
Usually Stage 2 HT
May present in young individuals
May have secondary causes
Not taking medication (liers)
Improper BP measurement
Excessive Na intake, Inadequate diuretic Rx.
Full doses of drugs not employed
Drug interactions – NSAIDs, SMA, OCP, OTC
Herbal remedies, Excessive alcohol use
Identify the above and correct
Secondary causes to be searched for
126
Case 29
Hypertensive emergencies
 HT emergency
 TOD Presentation
 Treatment
 Do not use
www.drsarma.in
Marked DBP elevation
Acute TOD present
Encephalopathy, MI, ACS, Pul Edema,
Eclampsia, stroke, head trauma, lifethreatening arterial bleeding, or aortic
dissection
With TOD immediate admission to ICU
IV Nitroprusside, Diazoxide, Labetolol
Without TOD Combination of 2 or 3 drugs
Close monitoring
Life style modification not now – no time
No sublingual nefedipine,
127
Case 30
Hypertensive with Acute CVA (Stoke)
 HT + CVA (Stroke)
 Rationale
 Treatment
www.drsarma.in
Marked DBP elevation
May be SAH, ICH, Acute Brain Infarction
In acute setting, no consensus on
treatment of elevated BP
HT at time of an acute stroke associated
with increased risk of cerebral hemorrhage
and edema, increased mortality
After acute ischemic stroke, cerebral
auto regulation affected
Active treatment of BP in the first 7 days
could worsen symptoms
Recommendation not to start HT Rx.
before 7 to 10 days after ischemic stroke
128
Current Indications for Alpha Blockers
1. Hypertension with BPH
2. In Pheochromoytoma before surgery
3. In the treatment of Ergot over dose
4. Raynaud’s syndrome and PVD, TAO
5. Vasospastic (prinzemetal Angina)
6. Diabetic neuropathy
7. Hypertensive smokers
8. Hypertension with Dyslipidemia
First dose syncope and Postural Hypotension
How to avoid ?
www.drsarma.in
129
Learning is a cyclical process
Each of these presentations
is a valuable learning
experience for me
Thank You all
www.drsarma.in
130