Download JNC 7 Organizational Structure - Karachi Institute of Heart Diseases

Current Concepts in
Pharmachotherapy in Hypertension
Brig Afsar Raza
FCPS (Medicine), FCPS( Cardiology), MRCP(UK),
CCST Cardiology (UK)
Commandant Army Cardiac Centre
Consultant Cardiologist & Physician
Army Cardiac Centre Lahore
Pakistan
Hypertension : High Prevalence
& Growing Incidence in Pakistan
• Accounts for over 100,000 deaths a year or
12% of all cause mortality .
• Overall 18% of adults in Pakistan suffer from
hypertension: 21.5% in urban areas and 16.2%
in rural areas.
• One in every 3 adults over age 45 suffer from
hypertension.
• Very few Pakistanis with hypertension (<3%) have
their B.P controlled.
PROCOR: 7/25/99 The National Health Survey in Pakistan published in 1998 by (PMRC)
Levels of blood-pressure control in different
countries: Only 3% controlled in Pakistan
Percent of Patients Controlled
*
100%
90%
80%
70%
60%
50%
40%
30%
20%
10%
0%
US
Germany
Finland
Spain
Australia
* Controlled defined as <140/90 mm Hg; other countries <160/95 mm Hg
J Hum Hypertens 1997;11(4):213-220
** 3% controlled: Data from Pakistan Hypertension League
Scotland
Canada
India
England
Pakistan**
Benefits of Lowering BP
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20–25%
Heart failure
50%
Benefits of Lowering BP
Heart Failure
Reduction: 50%
Stroke Reduction:
35-40%
5
MI Reduction:
20-25%
Ref : EWPHE, LANCET, 1985; 1349-1954 SHEP, JAMA’ 1991; 265: 3255-3264
To Prevent Target Organ Damage
 Heart
• Left ventricular hypertrophy
• Angina or prior myocardial infarction
• Prior coronary revascularization
• Heart failure
 Brain
• Stroke or transient ischemic attack
 Chronic kidney disease
 Peripheral arterial disease (PVD)
 Eye: Retinopathy
Benefits of Lowering BP
In stage 1 HTN and additional CVD risk factors, achieving
a sustained 12 mmHg reduction in SBP over 10 years will
prevent 1 death for every 11 patients treated.
Goals of Therapy
 Reduce CVD and renal morbidity and mortality.
 Treat to BP <140/90 mmHg or BP <130/80 mmHg in
patients with diabetes or chronic kidney disease.
 Achieve SBP goal especially in persons >50 years of age.
8
Blood Pressure Classification
BP Classification
SBP mmHg
BP mmHg
Normal
<120
and
<80
Prehypertension
120–139
or
80–89
Stage 1 Hypertension
140–159
or
90–99
Stage 2 Hypertension
>160
or
>100
Treatment
Overview
 Goals of therapy
 Lifestyle modification
 Pharmacologic treatment
• Algorithm for treatment of hypertension
 Followup and monitoring
Is it just BP control which is required or ......
Traditional
Treatment Approach
New
Treatment Approach
Hypertension
systemic disease
Hypertension
disease of blood vessels
Hemodynamics
altered
Vascular biology
altered
Treat
Blood Pressure
Control BP
& Treat vasculature
(Endothelium)
CV Risk Factors affect Prognosis & Guide Treatment
(JNC 7 Report)
>95% of hypertensives have
Other CV risk factors*
High-risk
Hypertension
95%
•Cigarette smoking
•Obesity
•Physical inactivity
•Dyslipidemia
•Diabetes mellitus
•Microalbuminuria or
estimated GFR <60 mL/min
•Age (>55 years for men,
>65 years for women)
•Family history of premature CVD
Hypertension with CV risk factors: Patients highly vulnerable
for JAMA,
target
JNC 7 Report
Mayorgan
21, 2003-damage
Vol 289, No. 19
*Stern N, et al. J Intern Med. 2000;203-210
Identifiable
Causes of Hypertension
 Sleep apnea
 Drug-induced or related causes
 Chronic kidney disease
 Primary aldosteronism
 Renovascular disease
 Chronic steroid therapy and Cushing’s syndrome
 Pheochromocytoma
 Coarctation of the aorta
 Thyroid or parathyroid disease
Lifestyle Modification
Modification
Weight reduction
Approximate SBP reduction
(range)
5–20 mmHg/10 kg weight loss
Adopt DASH eating plan
8–14 mmHg
Dietary sodium reduction
2–8 mmHg
Physical activity
4–9 mmHg
Moderation of alcohol
consumption/Smoking
2–4 mmHg
Classification and Management
of BP for adults
BP
classification
Normal
SBP*
mmHg
DBP*
mmHg
Lifestyle
modification
<120
and <80
Encourage
Initial drug therapy
Without compelling
indication
Prehypertension 120–139 or 80–89
Yes
No antihypertensive drug
indicated.
Stage 1
Hypertension
Yes
Thiazide-type diuretics for
most. May consider ACEI,
ARB, BB, CCB, or
combination.
Yes
Two-drug combination for
most† (usually thiazide-type
diuretic and ACEI or ARB or
BB or CCB).
Stage 2
Hypertension
140–159 or 90–99
>160
or >100
*Treatment determined by highest BP category.
†Initial combined therapy should be used cautiously in those at risk for orthostatic hypotension.
‡Treat patients with chronic kidney disease or diabetes to BP goal of <130/80 mmHg.
With compelling
indications
Drug(s) for compelling
indications. ‡
Drug(s) for the
compelling
indications.‡
Other antihypertensive
drugs (diuretics, ACEI,
ARB, BB, CCB) as
needed.
Special Considerations
 Compelling Indications
 Other Special Situations
•Obesity and the metabolic syndrome
• Peripheral arterial disease
• Hypertension in older persons
• Postural hypotension
• Hypertension in women
•Hypertension urgencies and emergencies
Compelling Indications
Compelling Indications for
Individual Drug Classes
Compelling Indication
Initial Therapy Options
Clinical Trial Basis
Heart failure
THIAZ, BB, ACEI, ARB, ALDO
ANT
ACC/AHA Heart Failure
Guideline, MERIT-HF,
COPERNICUS, CIBIS,
SOLVD, AIRE, TRACE,
ValHEFT, RALES
Postmyocardial
infarction
BB, ACEI, ALDO ANT
High CAD risk
BB, ACE, CCB
ACC/AHA Post-MI
Guideline, BHAT, SAVE,
Capricorn, EPHESUS
ALLHAT, HOPE, ANBP2,
LIFE, CONVINCE
Compelling Indications for
Individual Drug Classes
Compelling Indication
Initial Therapy Options
Clinical Trial Basis
Diabetes
ACE, ARB, CCB , THIAZ,
NKF-ADA Guideline,
UKPDS, ALLHAT
Chronic kidney disease
ACEI, ARB, CCB
NKF Guideline, Captopril
Trial, RENAAL, IDNT, REIN,
AASK
Recurrent stroke prevention
ACEI,ARBs, THIAZ,
PROGRESS
Other Special Situations
Hypertension in Older
Persons
 More than two-thirds of people over 65 have HTN.
 This population has the lowest rates of BP control
 Threshold for treatment Diastolic > 90mm Hg and systolic > 150-160
mm Hg over 3-6 months observation(despite life style intervention)
 Lower initial drug doses may be indicated to avoid symptoms
 Thiazide or CCB(Dihydroyridine). ACE or ARB may be added
Postural Hypotension
 Decrease in standing SBP >10 mmHg, when associated with
dizziness/fainting, more frequent in older SBP patients with diabetes,
taking diuretics or venodilators drugs.
 BP in these individuals should be monitored in the upright position.
 Avoid volume depletion and excessively rapid dose titration of drugs.
Hypertension in Women
 Oral contraceptives may increase BP, and BP should be checked
regularly. In contrast, HRT does not raise BP.
 Development of HTN—consider other forms of contraception.
 Pregnant women with HTN should be followed carefully. Methyldopa,
BBs, and vasodilators, preferred for the safety of the fetus. ACEI and
ARBs contraindicated in pregnancy.
Hypertension in Pregnancy
 May be due to pre existing essential HTN or pre-eclampsia.
 Methyl dopa is safe
 B Blockers are effective & safe in 3rd trimester
 Modified release prep of Nifedepine
 IV Labetalol for hypertensive crises
 ACE and ARBs best avoided
Accelerated Hypertension
(Diasstolic >140 mm Hg)
 Requires hospitalization.
 IV not necessary
 Rapid reduction not recommended can reduce organ perfusion;
cerebral or myocardial ischemia
 Long acting CCB(Amlodipine or modified release Nifedipine) or B
Blocker to start with to reduce BP 100-110 mm Hg. Then ACE/ARB
may be added
 Na Nitroprusside by infusion is the drug of choice if IV necessary
Pheochromocytoma
 Long term remedy is surgery.
 Alpha Blockers(Phenoxybenzamine) for short term management of
episodes
 Tachycardia can be controlled with careful use of BBs
 Phentolamine for short term during surgery
Causes of
Resistant Hypertension
 Improper BP measurement
 Excess sodium intake
 Inadequate diuretic therapy
 Medication
• Inadequate doses
• Drug actions and interactions (e.g., nonsteroidal anti-inflammatory
drugs (NSAIDs), illicit drugs, sympathomimetics, oral contraceptives)
• Over-the-counter (OTC) drugs and herbal supplements
 Excess alcohol intake
 Identifiable causes of HTN
ESH/ESC & ADA Guidelines
ADA Treatment Recommendations for Diabetic
Patients with Hypertension
 Recommended target blood pressure
• Systolic <130 mm Hg
• Diastolic <80 mm Hg
 Drug therapy mandatory above 140 mm Hg systolic and 90 mm Hg
diastolic
 Recommended first-line agents for patients with microalbuminuria or
clinical albuminuria
• ARBs and ACE-Is
ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker.
American Diabetes Association. Diabetes Care. 2002;25(Suppl 1):S71-S73.
ADA Treatment Recommendations for Diabetic
Nephropathy
 Both ACE-Is and ARBs are first-line agents for treatment of
albuminuria/nephropathy
 Initial choice in diabetic nephropathy for hypertensive and
nonhypertensive patients with type 1 diabetes
• ACE-Is
 Initial choice in diabetic nephropathy for hypertensive patients with
microalbuminuria or clinical albuminuria and type 2 diabetes
• ARBs
 If one class is not tolerated, the other should be substituted
American Diabetes Association. Diabetes Care. 2002;25(Suppl 1):S85-S89.
ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker.
ACE Inhibition
Beyond Hypertensive Control
Endothelium-Focus of New Research
Arteriole
lumen
Endothelium
Largest organ of the human body
Causes and consequences of Endothelial
Dysfunction
Heart failure
Vasospasm
(coronory, cerebral)
Diabetes
Reocclusion
Hypertension
Endothelial
dysfunction
Hyperhomocystenemia
Reperfusion
injury
Peripheral artery
disease
Hyperlipidemia
Immune
reaction
Inflammatory
disease
Atherosclerosis
Adopted from Rubanyi GM. J Cardiovasc Pharmacol. 1993;22(suppl 4):S1-S4
Additional Considerations in
Antihypertensive Drug Choices
Potential favorable effects
 Thiazide-type diuretics useful in slowing demineralization in
osteoporosis.
 BBs useful in the treatment of atrial tachyarrhythmias/fibrillation,
migraine, thyrotoxicosis (short-term), essential tremor, or perioperative
HTN.
 CCBs useful in Raynaud’s syndrome and certain arrhythmias.
 Alpha-blockers useful in prostatism.
 Spironlactone in Conn,s syndrome
Additional Considerations in
Antihypertensive Drug Choices
Potential unfavorable effects
 Thiazide diuretics should be used cautiously in gout or a history of
significant hyponatremia.
 BBs should be generally avoided in patients with asthma, reactive
airways disease, or second- or third-degree heart block.
 ACEIs and ARBs are contraindicated in pregnant women or those likely
to become pregnant.
 ACEIs should not be used in individuals with a history of angioedema.
 Aldosterone antagonists and potassium-sparing diuretics can cause
hyperkalemia.
Conclusion
 According to baseline BP and presence or absence of
complications, therapy can be initiated either with a low
dose of a single agent or with a low-dose combination of 2
agents
 Most patients with hypertension will require 2 or more
antihypertensive drugs to achieve BP goals
 Choice of therapy has to be individualized keeping in view
the associated co morbid conditions
Chobanian AV et al. JAMA. 2003;289:2560-2572.
Guidelines Committee. J Hypertens. 2003;21:1011-1053.
Thank You
Trends in Awareness, Treatment, and
Control of Hypertension in the US*
100
1976-1980
90
1988-1991
80
73%
70
Percentage
of Population
60
1991-1994
68% 70%
55% 54%
51%
1999-2000
59%
50
40
29% 27% 34%
31%
30
20
10%
10
0
Aware
Treated
Controlled†
*Data for 1999-2000 were computed (M. Wolz, unpublished data, 2003) from the National Heart, Lung, Blood Institute
and data for National Health and Nutrition Examination Surveys II and III (phases 1 and 2) are from The Sixth Report
of the Joint National Committee on Prevention Detection, Evaluation and Treatment of High Blood Pressure. High blood
pressure is systolic blood pressure of 140 mm Hg or diastolic blood pressure 90 mm Hg, or taking antihypertensive
medication.
†Systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg.
Chobanian AV et al. JAMA. 2003;289:2560-2572.
Effect of Systolic and Diastolic Blood Pressure on
Coronary Heart Disease Mortality: MRFIT
48.3
37.4
31.0
43.8
25.5
23.8
20.6
38.1
16.9
25.3
13.9
10.3
25.2
12.6
8.8
90-99
24.9
12.8
11.8
100+
80.6
11.8
8.5
80-89
9.2
75-79
160+
140-159
120-139
70-74
<70
Adapted from Neaton JD, Wentworth D. Arch Intern Med. 1992;152:56-64.
<120
CVD Risk Factors
 Hypertension*
 Cigarette smoking
 Obesity* (BMI >30 kg/m2)
 Physical inactivity
 Dyslipidemia*
 Diabetes mellitus*
 Microalbuminuria or estimated GFR <60 ml/min
 Age (older than 55 for men, 65 for women)
 Family history of premature CVD
(men under age 55 or women under age 65)
*Components of the metabolic syndrome.
CVD Risk
 HTN prevalence ~ 50 million people in the United States.
 The BP relationship to risk of CVD is continuous, consistent, and
independent of other risk factors.
 Each increment of 20/10 mmHg doubles the risk of CVD across the
entire BP range starting from 115/75 mmHg.
 Prehypertension signals the need for increased education to reduce
BP in order to prevent hypertension.
ESH/ESC 2003: Cardiovascular Risk
Stratification
Blood Pressure (mm Hg)
Other Risk Factors and
Disease History
No other risk factors
1-2 risk factors
≥3 risk factors,
target organ damage, or
diabetes
Associated clinical
conditions
Normal
SBP 120-129
or DBP 80-84
High-Normal
SBP 130-139
or DBP 85-89
Grade 1
SBP 140-159
or DBP 90-99
Grade 2
SBP 160-179
or DBP 100-109
Grade 3
SBP ≥180
or DBP ≥110
Average
risk
Average
risk
Low
added risk
Moderate
added risk
High
added risk
Low
added risk
Low
added risk
Moderate
added risk
Moderate
added risk
Very high
added risk
Moderate added
risk
High
added risk
High
added risk
High
added risk
Very high
added risk
High
added risk
Very high added
risk
Very high
added risk
Very high
added risk
Very high
added risk
Guidelines Committee. J Hypertens. 2003;21:1011-1053.
JNC Classification of Blood Pressure
for adults age 18 and older
Category
Systolic
(mmHg)
Diastolic
(mmHg)
Optimal
Normal
High-normal
<120
<130
130-139
and
or
and
85-89
140-159
160-179
>180
or
or
or
90-99
100-109
110
Hypertension
Stage 1
Stage 2
Stage 3
<80
<85
Relative risk of death
In hypertension With Controlled BP
Mortality Risk is Still Higher Than in Normotensive
2
Male
Female
1.5
1
1
1
1.36 1.3
0.5
Normotensives
Hypertensives,
treated and
controlled
1.82 1.97
Hypertensives
treated and
not controlled
0
High risk of mortality in patients with controlled BP points out to other causes
of target Organ damage (e.g endothelial dysfunction)
Hawlk RJ et al, Hypertension. 1989;13(suppl):1-20-1-32.
Algorithm for Treatment of Hypertension
Lifestyle Modifications
Not at Goal Blood Pressure (<140/90 mmHg)
(<130/80 mmHg for those with diabetes or chronic kidney disease)
Initial Drug Choices
Without Compelling
Indications
With Compelling
Indications
Stage 1 Hypertension
Stage 2 Hypertension
(SBP 140–159 or DBP 90–99 mmHg)
Thiazide-type diuretics for most.
May consider ACEI, ARB, BB, CCB,
or combination.
(SBP >160 or DBP >100 mmHg)
2-drug combination for most (usually
thiazide-type diuretic and
ACEI, or ARB, or BB, or CCB)
Not at Goal
Blood Pressure
Optimize dosages or add additional drugs
until goal blood pressure is achieved.
Consider consultation with hypertension specialist.
Drug(s) for the compelling
indications
Other antihypertensive drugs
(diuretics, ACEI, ARB, BB, CCB)
as needed.
ACE InhibitorsBenefits Beyond Anti
Hypertensive Effects
“ Data collected from various studies suggested that
treatment of hypertension with ACE Inhibitors
could prevent endothelial dysfunction independent
of systemic anti hypertensive effect.”
Medical clinics of North America 1998
Circulating vs tissue ACE
Circulating ACE (endocrine)
•Plasma
Tissue ACE (autocrine/paracrine)
•Vasculature (endothelium)
•CNS
•Adrenal
•Heart
•Kidney
•Reproductive organs
•Lung
Circulating ACE
10%
Tissue ACE
90%
Tissue ACE Mainly Responsible For Target Organ Damage
Dzau VJ.Arch Intern Med. 1993;153:937-942
ACE Inhibition Vasculoprotective Effect
Kininogens
Angiotensinogen
Kallikreinin
Renin
Angiotensin I
Bradykinins
ACE Inhibition
Angiotensin II
Inactive Peptides
ACE Inhibition in vascular endothelium
Ang II; Bradykinin; NO
Laboratory Tests
 Routine Tests
• Electrocardiogram
• Urinalysis
• Blood glucose, and hematocrit
• Serum potassium, creatinine, or the corresponding estimated GFR,
and calcium
• Lipid profile, after 9- to 12-hour fast, that includes high-density and
low-density lipoprotein cholesterol, and triglycerides
 Optional tests
• Measurement of urinary albumin excretion or albumin/creatinine ratio
 More extensive testing for identifiable causes is not generally indicated
unless BP control is not achieved
(JNC 7)
Importance of Endothelium in Vascular Damage

In patients with hypertension permeability
of endothelium is altered

Endothelium - Source of a host of Vasoactive Substances & growth regulating
peptides
• Angiotensin II
• Bradykinin
Healthy Endothelium
• Endothelin
• Nitric Oxide
• Insulin Growth Factor
• Platelet Derived Growth Factor

Many of these factor have been incriminated
in the pathogenesis of Vascular Damage
Damaged Endothelium
Medical Clinics of North America Vol 18, # 5, 1997 -1117
Endothelial Function / Vascular Health
Healthy endothelium maintains a balance between
opposing states :
• Dilation vs constriction
• Growth inhibition vs growth promotion
• Antithrombosis vs prothrombosis
• (antifibrinolysis vs profibrinolysis)
• Anti-inflammation vs pro-inflammation
• Antioxidation vs pro-oxidation
Lusher TF, Barton M. Clin Cardiol. 1997;10 (supplII):11-3-11-10.Vane JR et al.N Eng J Med. 1990;323:27-36.
Harrison DG. Clin Cardiol. 1997;10(suppl):II-11-II-17