Transcript hypertension

HYPERTENSION
TARIQ HADDADIN,MD,FACC,FSCAI
ASSISSTANT PROFESSOR OF INTERNAL
MEDICINE
CHIEF,INTERVENTIONAL CARDIOLOGY
EAST TENNESSEE STATE UNIVERSITY
DISCLOSURE
NOTHING TO
DISCLOSE
THANK YOU
WHAT’S HYPERTENSION
 Definition: a usual BP of 140/90mmHg or
higher, a BP level for which the benefits of
pharmacological therapy have been definitely
established in randomized placebocontrolled trials.
Blood Pressure Classification
BP Classification
SBP mmHg
DBP 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
SYMPTOMS
 NO SYMPTOMS.
 IT’S A SILENT
KILLER.
Rationale for Lowering Blood Pressure
Hypertension
Prevalence
Prevalence of Hypertension
in the United States by Age Group*
†
Age
*Based on data from the 19992000 National Health and Nutrition Examination Survey.
Hypertension is defined as blood pressure 140/90 mm Hg or as receiving antihypertensive
treatment.
†Low reliability due to large relative error.
Fields LE, et al. Hypertension. 2004;44:398-404.
Risk of Hypertension (%)
Lifetime Risk of Developing Hypertension
Among Adults at 65 Years of Age*
Men
Women
Years
*Residual lifetime risk of developing hypertension among adults
at 65 years of age with a blood pressure <140/90 mm Hg.
Vasan RS, et al. JAMA. 2002;287:1003-1010.
Adults (%)
Hypertension Control Rates Are
Slowly Improving (NHANES Data)
19761980
19881991
19911994
19992000
20012002
20032004
*Controlled blood pressure was defined as <140/90 mm Hg and expressed as a %
of all hypertensives. NHANES = National Health and Nutrition Examination Survey.
Chobanian AV, et al. JAMA. 2003;289:2560-2572; Ong KL, et al.
Hypertension. 2007;49:69-75; Ostchega Y, et al. NCHS Data
Brief. 2008;(3):1-8.
20052006
Systolic Blood Pressure Control Rates from
Selected Cardiovascular Outcomes Trials
Blood Pressure Control Among Hypertensive Patients
in the United States Could Be Improved
Clinical Trial
Systolic Blood Pressure
<140 mm Hg
ALLHAT
64%
INVEST
71%
CONVINCE
66%
ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial; INVEST =
International Verapamil SR–Trandolapril Study; CONVINCE = Controlled Onset Verapamil
Investigation of Cardiovascular Endpoints; SBP = systolic blood pressure
ALLHAT Collaborative Research Group. JAMA. 2002;288:2981-2997;
Black HR, et al. JAMA. 2003;289:2073-2082; Dahlöf B, et al. Lancet.
2002;359:995-1003; Pepine CJ, et al. JAMA. 2003;290:2805-2816.
Cardiovascular Mortality Risk
Increases as Blood Pressure
8x
*
Rises
8
Cardiovascular
Mortality Risk
7
6
5
4x
4
3
2x
2
1
0
115/75
135/85
155/95
175/105
Systolic/Diastolic Blood Pressure (mm Hg)
*Measurements taken
in individuals aged 40–69 years, beginning with a blood
pressure of 115/75 mm Hg.
Lewington S, et al. Lancet. 2002;360:1903-1913;
Chobanian AV, et al. JAMA. 2003;289:2560-2572.
Cumulative Incidence of Major
Cardiovascular Events (%)
Impact of High-Normal Blood Pressure on Risk of Major
Cardiovascular Events* in Men
16
Blood Pressure:
14
High-Normal
130–139/85–89 mm Hg
12
Normal
10
120–129/80–84 mm Hg
8
Optimal
6
<120/80 mm Hg
4
2
0
0
2
4
6
8
10
Time (Years)
*Defined as death due to cardiovascular disease or as having recognized
myocardial infarction, stroke, or congestive heart failure.
Vasan RS. N Engl J Med. 2001;345:1291-1297.
12
Patient-Related Barriers to Effective
Antihypertensive Treatment


Increased susceptibility
 Advanced age
 Obesity
Secondary causes (less common)
 Sleep apnea
 Drug side effects
 Chronic kidney disease
 Primary aldosteronism
 Renovascular disease
 Cushing syndrome
 Pheochromocytoma
 Coarctation of the aorta
 Thyroid/parathyroid disease
Wang TJ, Vasan RS. Circulation. 2005;112:1651-1662;
Chobanian AV, et al. JAMA. 2003;289:2560-2572.

Limited access to health care
 Lack of health insurance
 Lack of a regular provider

Nonadherence to therapy
 Knowledge deficits
 Medication cost
 Complicated regimens
 Side effects
 Medication not taken by patient
 Poor physician-patient
communication
 Lack of social support
Complications of Hypertension:
End-Organ Damage
Hypertension
LVH, CHD, CHF
Hemorrhage,
Stroke
Retinopathy
CHD = coronary heart disease
CHF = congestive heart failure
LVH = left ventricular hypertrophy
Chobanian AV, et al. JAMA. 2003;289:2560-2572.
Peripheral
Vascular
Disease
Renal Failure,
Proteinuria
Benefits of Lowering BP
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20–25%
Heart failure
50%
Relationship of Hypertension
to Its Comorbidities
Comorbidity
Relationship to Hypertension
Coronary artery disease
50% of patients with coronary artery disease
have hypertension
Left ventricular hypertrophy
15% to 20% of hypertensive adults have an
increased left ventricular mass
Ischemic stroke
77% of patients who have a first stroke have
a blood pressure >140/90 mm Hg
Chronic kidney disease
8% to 15% of hypertensive adults have
decreased renal function
Diabetes
75% of added cardiovascular risk in diabetic
patients is attributable to hypertension
Peripheral artery disease
74% of patients with peripheral artery
disease have hypertension
Diamond JA, Phillips RA. Hypertens Res. 2005;28:191-202;El-Atat F, et al. Curr Hypertens
Rep. 2004;6:215-223; Pepine CJ. Am J Cardiol. 1998;82(3A):21H-24H; Rosamond W, et al.
Circulation. 2007;115:69-171; Segura J, et al. Curr Opin Nephrol Hypertens. 2004;13:495-500;
Selvin E, Erlinger P. Circulation. 2004;110:738-743.
Effects of Systolic and Diastolic Blood
Pressures on CHD Mortality: MRFIT*
48.3
80.6
CHD Death Rate
Per 10,000
Person-Years
37.4
34.7
31.0
43.8
38.1
25.5
23.8
24.6
25.2
16.9
20.6
24.9
13.9
10.3
12.8
12.6
11.8
90-99
*Data shown only for
160+
11.8
8.8
100+
Diastolic
Blood Pressure
(mm Hg)
25.3
8.5
80-89
140-159
9.2
120-139
75-79
70-74
316,099 white men 35 to 57 years
of age who were followed for a mean of 12 years.
CHD = coronary heart disease
MRFIT = Multiple Risk Factor Intervention Trial
Neaton JD, et al. Arch Intern Med. 1992;152:56-64.
<70
<120
Systolic
Blood Pressure
(mm Hg)
Coronary Artery Disease (CAD) Progression
Is Linked to Systolic Blood Pressure*
n = 247
*The composite regression line represents blood pressure values in patients with
CAD after either amlodipine or enalapril therapy. A systolic blood pressure in
the range of ~120 to 140 mm Hg corresponded to no net progression of CAD.
Sipahi I, et al. J Am Coll Cardiol. 2006;48:833-838.
Risk of Stroke Death According to
Blood Pressure (mm Hg): MRFIT
Relative Risk of Stroke
Death
†
Systolic Blood Pressure (SBP)
Diastolic Blood Pressure (DBP)
†
†
†
*
1
2
3
4
DBP
<112
<71
112
71
5
6
*
*
*
7
8
118
76
121
79
125
81
129
84
MRFIT = Multiple Risk Factor Intervention Trial; *P < 0.01; †P < 0.001.
Stamler J, et al. Arch Intern Med. 1993;153:598-615;
He J, Whelton PK. Am Heart J. 1999;138(Pt 2):211-219.
9
10
(Highest 10%)
Decile
(Lowest 10%)
SBP
*
†
132
86
137
89
142
92
≥151
≥98
Incidence of Fatal and Nonfatal Stroke
The Anglo-Scandinavian Cardiac Outcomes Trial
Proportion of
Stroke Events (%)
-----
Atenolol-Based Regimen (422 Events)
Amlodipine-Based Regimen (327 Events)
p = 0.0003
Number
At Risk
Time (Years)

Amlodipine
Atenolol
9639
9618
9483
9461
Dahlof B, et al. Lancet. 2005;355:895-906.
9331
9274
9156
9059
8972
8843
7863
7720
Incidence of ESRD by Systolic Blood Pressure: Multiple Risk
Incidence of ESRD per 100,000
Person-Years (%)
Factor Intervention Trial*
White Men (n = 300,645)
83.1
Black Men (n = 20,222)
37.2
27.3
26.2
15.8
5.4
<117
5.4
117-123
9.1
124-130
14.2
131-140
Systolic Blood Pressure (mm Hg)
*The original cohort of
332,544 men included 11,677 men in other ethnic groups
whose data are excluded from this comparison.
ESRD = end-stage renal disease
Klag MJ, et al. JAMA. 1997;277:1293-1298.
32.4
>140
Blood Pressure Reduction Slows the Progression of Nondiabetic Kidney
Disease: The MDRD Study
Study
Group
Target
Mean
Arterial
BP*
(mm Hg)
Achieved
Mean
Achieved
Arterial BP Systolic BP
(mm Hg
(mm Hg
± SD)
± SD)
Achieved
Diastolic BP
(mm Hg
± SD)
Number
with
Kidney
Failure
(%)
Usual BP
Control
(n=408)
<107 or
<113
98.4
± 7.4
133.8
± 14.9
80.7
± 7.2
286
(70)
Tighter BP
Control
(n=432)
<92 or
<98
93.3
± 6.0
126.2
± 13.6
76.9
± 6.4
268
(62)†
*The lower value was assigned to participants 60 years of age or younger, and the higher
value was assigned to participants 61 years of age or older.
†Unadjusted hazard ratio = 0.78 (95% CI, 0.66 to 0.93; P = 0.0056); adjusted hazard ratio =
0.68 (95% CI, 0.57 to 0.82; P < 0.001).
BP = blood pressure; SD = standard deviation;
MDRD = Modification of Diet in Renal Disease Study
Sarnak MJ, et al. Ann Intern Med. 2005;142:342-351.
Diabetes Increases Hypertension-Related
Cardiovascular Risk: MRFIT
Cardiovascular Mortality Rate
per
10,000 Person-Years
Nondiabetic Men (n = 342,815)
Diabetic Men (n = 5,163)
<120
120139
140159
160179
Systolic Blood Pressure (mm Hg)
MRFIT = Multiple Risk Factor Intervention Trial
Stamler J, et al. Diabetes Care. 1993;16:434-444.
180199
≤200
Antihypertensive Treatment Can Reduce Cardiovascular Events in
Diabetic Patients
Hypertension Optimal Treatment Study
Achieved
SBP*
Achieved
DBP*
(mm Hg)
(mm Hg)
(mm Hg)
Patients
with
Diabetes
 90
143.7
85.2
501
 85
141.4
83.2
501
 80
139.7
81.1
499
*Mean
of all blood pressures for all study
patients in the blood pressure subgroups from
6 months of follow-up to the end of the study.
DBP = diastolic blood pressure
SBP = systolic blood pressure
†Events include all myocardial infarctions, all
strokes, and all other cardiovascular deaths.
Hansson L, et al. Lancet. 1998;351:1755–1762.
P = 0.005
Events† Per 1000 Patient-Years
Target
DBP
Event Rates for Select End Points with Tight
Versus Less-Tight Blood Pressure Control
United Kingdom Prospective Diabetes Study
Tight Control* (n = 758)
P = 0.005
Events per
1000 Patient-Years
Less-Tight Control† (n = 390)
P = 0.02
P = 0.009
P = 0.01
Any Diabetes-Related
End Point
DiabetesRelated Death
*Mean achieved blood pressure = 144/82 mm Hg.
†Mean achieved blood pressure =
154/87 mm Hg.
UKPDS Group. BMJ. 1998;317:703–713, 713-720.
Stroke
Microvascular
Complications
Hypertension Increases the Risk of Symptomatic
Peripheral Artery Disease
Odds Ratio
(95% CI)
Male Gender
Age/10 Years
Diabetes
Smoking
Hypertension
Dyslipidemia
Hyperhomocysteinemia
Race (Asian/Hispanic/Black vs. White)
C-Reactive Protein
Renal Insufficiency
CI = confidence interval
Norgren L , et al. J Vasc Surg. 2007;45(Suppl 1):S5A-S67A.
1
2
3
4
Current Blood Pressure Targets
for Various Chronic Conditions
Uncomplicated
Hypertension
Chronic Kidney Disease
Coronary Artery Disease
Diabetes
≤140
Systolic
Blood
Pressure
≤90
≤130
≤80
mm Hg
American Diabetes Association. Diabetes Care. 2003;26:S80-S82; Hansson L, et al. Lancet.
1998;351:1755-1762; National Kidney Foundation. Am J Kidney Dis. 2002;39(2 Suppl 1):S1S266;
Rosendorff C, et al. Circulation. 2007;115:2761-2788.
Diastolic
Blood
Pressure
SUMMARY
 The risk of fatal and nonfatal cardiovascular and renal events (stroke, coronary
artery disease, end-stage renal disease) is closely linked to both systolic and
diastolic blood pressure
 Coronary artery disease events and strokes are also linked to both blood pressure
and levels of low-density lipoprotein cholesterol
 Cardiovascular and renal risks are exaggerated in patients with diabetes mellitus
 Among hypertensive patients, the extent to which cardiovascular and renal
events are reduced is closely linked to the extent to which blood pressure is
reduced
 Evidence from clinical trials supports the current recommendations to reduce
blood pressure to 130/80 mm Hg in patients who have diabetes, chronic kidney
disease, and coronary artery disease
DO DIET AND
EXERCISE WORK?
ASH Position Paper :Dietary Approaches to
Lower Blood Pressure.
Lawrence J. Appel, MD, MPH, on Behalf of
the American Society of
Hypertension Writing Group
A substantial body of evidence has implicated
several aspects of diet in the pathogenesis of
elevated blood pressure (BP). Well-established
risk factors for elevated BP include excess salt
intake, low potassium intake, excess weight, high
alcohol consumption, and suboptimal dietary
pattern. African Americans are especially sensitive
to the BP-raising effects of excess salt intake,
insufficient potassium intake, and suboptimal
diet. In this setting, dietary changes have the
potential to substantially reduce racial disparities
in BP and its consequences. I
In nonhypertensives, dietary
changes can lower BP and delay, if not prevent,
hypertension.
In uncomplicated stage I hypertension, dietary
changes serve as initial treatment
before drug therapy.
In hypertensive individuals
already on drug therapy, lifestyle modifications
can further lower BP
Lifestyle Modification
Recommendation
 Weight loss
 For overweight or obese
persons, lose weight,
ideally attaining a body
mass index<25 kg ⁄ m2
 For nonoverweight
persons, maintain
desirable body mass index
<25 kg ⁄ m
Lifestyle modification
Recommendation
 Reduced sodium intake
 Lower sodium intake as
much as possible, with a
goal of no more than 2300
mg ⁄ d in the general
population and no more
than 1500 mg ⁄ d in blacks,
middle- and older-aged
persons, and individuals
with hypertension,
diabetes, or chronic kidney
disease
Lifestyle modification
Recommendation
 DASH-style dietary pattern
 Consume a diet rich in
fruits and vegetables (8–10
servings ⁄ d), rich in low-fat
dairy products (2–3
servings ⁄ d), and reduced
in saturated fat and
cholesterol.
Lifestyle modification
Recommendation
 Increased potassium intake
 Increase potassium intake
to 4.7 gm ⁄ d, which is also
the level provided in the
DASH-
 DASH, Dietary Approaches
to Stop Hypertension diet
Lifestyle modification
Recommendation
 Moderation of alcohol
 For those who drink alcohol,
intake
consume 2 alcoholic drinks per
day (men) and 1 alcohol
drink/day (women)
 One alcoholic drink is defined
as 12 oz of regular beer, 5 oz
 of wine (12% alcohol), or 1.5 oz
of 80 proof distilled spirits.
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
2–4 mmHg
EXERCISE DOES WORK
 Any exercise programs that involve endurance
activities, such as walking, jogging, running, or
cycling, coupled with resistance training can help
prevent the development of hypertension and even
lower blood pressure in adults.
 But even a single exercise session provides an
immediate reduction in blood pressure that can last
for up to 22 hours.
DON’T FORGET SMOKING AS A CAUSE
OF HYPERTENSION
 Tobacco use is the most common cause of avoidable
cardiovascular mortality worldwide .
 The immediate noxious effects of smoking are related to
sympathetic nervous overactivity, which increases
myocardial oxygen consumption through a rise in blood
pressure, heart rate, and myocardial contractility.
 With each cigarette, the blood pressure rises transiently
and the pressor effect may be missed if the blood pressure
is measured 30 minutes after the last smoke. The transient
rise in blood pressure may be most prominent with the
first cigarette of the day even in habitual smokers. In one
study of normotensive smokers, there was an average
elevation in systolic pressure of 20 mmHg after the first
cigarette
A CIGARETTE WITH
A CUP OF COFFEE
Furthermore, ambulatory blood pressure monitoring
suggests an interactive effect between smoking and
coffee drinking in patients with mild essential
hypertension, resulting in a mean elevation in
daytime systolic pressure of approximately 6.0
mmHg
Principles of Antihypertensive
Therapy
Classes of Antihypertensive Drugs





Aldosterone receptor
antagonists (blockers)
Angiotensin II antagonists
Angiotensin-converting
enzyme inhibitors
-Blockers
 1-Selective
 Nonselective
-Blockers
 -1/-2
 -1 predominant
 /
 Intrinsic
sympathomimetic
activity

Calcium channel antagonists
 Nondihydropyridine
 Dihydropyridine

Central 2 agonists

Direct renin inhibitors

Direct vasodilators

Diuretics
 Thiazide-type
 Loop-type
 Potassium-sparing

Ganglionic blockers
Antihypertensive Drug Classes: Action Sites
Blood
Pressure
=
Cardiac
Output
Antihypertensive Drug Classes
-Blockers

Total Peripheral
Resistance
-Blockers
ACE Inhibitors
AT1 Blockers
Direct renin inhibitors
1-Blockers
2-Agonists
Non-DHP
CCBs
Diuretics
Diuretics
Sympatholytics
ACE = angiotensin-converting enzyme; AT1 = angiotensin type 1;
CCBs = calcium channel blockers; DHP = dihydropyridine
All CCBs
Vasodilators
Recommended Drug Classes for Adults with Hypertension and
a Related Comorbidity
Compelling
Indicator*
Diuretic
Heart failure

Prior myocardial
infarction
-Blocker
ACE
Inhibitor
ARB








Diabetes







†
Prior stroke



High risk of
coronary disease
Chronic kidney
disease
CCB
Aldosterone
Antagonist


*Based on documented benefits from outcome studies or on existing clinical guidelines; each compelling
indicator is managed in parallel with hypertension.
† When used in conjunction with a diuretic.
ACE = angiotensin-converting enzyme; ARB = angiotensin receptor blocker;
CCB = calcium channel blocker
Chobanian AV, et al. JAMA. 2003;289:2560-2572. Copyright © 2003
American Medical Association. All rights reserved.
JNC-7 Report: Treatment Algorithm
Initial Drug Choices
No Compelling
Indication
Stage 1 HTN
Stage 2 HTN
• SBP 140159 mm Hg, DBP 9099 mm
Hg
 SBP ≥160 mm Hg , DBP ≥100 mm Hg
• Usually thiazide-type diuretic
 Usually thiazide-type diuretic and
• Also consider ACEI, ARB, BB, or CCB
alone or in combination
 2-drug combination
ACEI, ARB, BB, or CCB*
*More recent data suggest that other options may be considered.
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor blocker;
BB = -blocker; CCB = calcium channel blocker; DBP = diastolic blood pressure; HTN = hypertension; JNC = Joint
National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure; SBP = systolic
blood pressure
Chobanian AV, et al. JAMA. 2003;289:2560-2572. Copyright © 2003
American Medical Association. All rights reserved.
Pharmacokinetic Terms and Their Definitions
Maximum
Effective
Dose*
Drug Effect (% of Maximum)
100%
Minimum effective dose:
The dose that produces some
detectable effect.
DoseResponse
Curve
75%
Maximum effective dose:
The dose beyond which there is no
additional effect.
ED50
50%
Minimum
Effective
Dose*
25%
Area
Under
the
Curve
0%
1
10
102
103
104
[Relative Drug Concentration]
*Dose = the amount of drug that produces the
drug concentration illustrated in the graph.
Reprinted from Taylor AA, Pool JL. Semin Nephrol.
2005;25:215-226. Copyright © 2005 Elsevier.
ED50 (50% effective dose):
The dose that produces 50% of the
maximum effect.
Area under the curve:
An estimate of the range of
concentrations over which a drug is
effective.
Supine Blood Pressure: No Apparent Maximum Dose
Response to Diltiazem
70
Patients Responding (%)
Supine DBP <90 mm Hg
60
Supine DBP <90 mm Hg or a decrease >10 mm Hg
50
40
30
20
10
0
Placebo
90120
180240
Dose (mg/day)
DBP = diastolic blood pressure
Pool PE. Clin Cardiol. 2000;23:18-23. Copyright © 2000.
Reprinted with permission of John Wiley & Sons, Inc.
360
480540
Drug Effect or Adverse Effect (% of
Maximum)
Therapeutic Goal: Use Doses that
Maximize Drug Effects and Minimize Adverse Effects
100%
 Adverse effects usually
occur at doses greater
than the minimally
effective dose and
increase in frequency
and/or severity with
increasing doses
75%
Dose with
Minimum
Adverse
Effects*
50%
25%
Adverse
Effects
0%
1
10
102
103
104
[Relative Drug Concentration]
*Dose = the amount of drug that produces the
drug concentration illustrated in the graph.
Reprinted from Taylor AA, Pool JL. Semin Nephrol. 2005;25:215226. Copyright © 2005 Elsevier.
 Treat with a dose that
provides the greatest
effect with the fewest
adverse effects
Drug Effect or Adverse Effect (% of
Maximum)
Higher Drug Doses Increase Therapeutic Effects but Also
Adverse Effects
100%
100%
75%
75%
Dose with
Minimum
Adverse
Effects*
50%
25%
Higher
Dose*
50%
Adverse
Effects
0%
25%
Adverse
Effects
0%
1
10
102
103
104
[Relative Drug Concentration]
1
10
102
104
[Relative Drug Concentration]
*Dose = the amount of drug that produces the drug concentration illustrated in the graph.
Reprinted from Taylor AA, Pool JL. Semin Nephrol.
2005; 25:215-226. Copyright © 2005 Elsevier.
103
0
4.1
-5
3.9
-10
3.7
-15
3.5
-20
Systolic Blood Pressure
3.3
Serum Potassium
-25
3.1
0.0
12.5
25
50
100
Daily Chlorthalidone Dose (mg)
Carney S, et al. Med J Aust. 1976;2:692-693.
200
Serum Potassium (mEq/L)
Change in Systolic Blood
Pressure (mm Hg)
Changes in Systolic Blood Pressure and Serum
Potassium Level with Increasing Doses of
Chlorthalidone
Drug Effect or Adverse Effect (% of
Maximum)
Drug Combinations Can Increase Therapeutic Effects
Without Increasing Adverse Effects (AEs)*
100%
100%
75%
75%
Drugs A+B
Effect
Additive
Therapeutic
Effect
Drug A
Effect
50%
50%
25%
Drug A
Adverse
Effects
0%
1
10
102
103
104
[Relative Drug Concentration†]
Drug B
Adverse
Effects
Reduced
Adverse
Effect
Rate
Drugs
A+B
Adverse
Effects
Drug B
Effect
25%
0%
1
10
102
103
104
[Relative Drug Concentration†]
*The solid pink line represents the combined therapeutic effect and the dotted fuchsia line represents the combined adverse
effects for drugs A and B together.
†Dose
= the amount of drug that produces the drug concentration illustrated in the graph.
Reprinted from Taylor AA, Pool JL. Semin Nephrol.
2005;25:215-226. Copyright © 2005 Elsevier.
Blood Pressure Reduction (mm
Hg)*
Adding HCTZ to Eprosartan Provides Additional
Blood Pressure Control
0
Eprosartan
(600 mg)
-2
-4
Eprosartan (600 mg)
+ Hydrochlorothiazide
(12.5 mg)
-2.1
-3.6
-5.0
-6
-8
-10
-12
Supine SBP
Supine DBP
-14
*Mean reduction in blood pressure at 8 weeks.
DBP = diastolic blood pressure; HCTZ = hydrochlorothiazide;
SBP = systolic blood pressure
Sachse A, et al. J Hum Hypertens. 2002;16:169-176.
-10.0
Safety Profile of Telmisartan + HCTZ Is
Better Than That of HCTZ Alone
Telmisartan Monotherapy (n = 209)
HCTZ Monotherapy (n = 121)
Telmisartan + HCTZ (n = 414)
Adverse Events (%)
10
8
6
4
2
0
Headache
Dizziness
HCTZ = hydrochlorothiazide
McGill JB , Reilly PA. Clin Ther. 2001;23:833-850.
Fatigue
Hypokalemia
Drug Combinations Can Enhance Therapeutic Effects
While Reducing Adverse Effects*
100%
Drug Effect or Adverse Effect (% of
Maximum)
100%
Drugs A+B
Drug A
75%
75%
50%
50%
25%
25%
0%
0%
1
10
102
103
104
[Relative Drug Concentration†]
Additive
Therapeutic
Effect
Reduced
Adverse
Effect
Rate
1
10
102
103
104
[Relative Drug Concentration†]
*Some drug combinations yield a greater therapeutic effect than does either drug alone and reduced adverse effects
(dotted fuchsia line) when compared to those due to each drug (dotted blue and
dotted yellow lines). The solid lines depict the therapeutic effects of drug A (yellow), drug B (blue), and drugs A and B
combined (pink).
† Dose = the amount of drug that produces the drug concentration
illustrated in the graph.
Reprinted from Taylor AA, Pool JL. Semin Nephrol.
2005;25:215-226. Copyright © 2005 Elsevier.
Change in Mean 24-Hour Systolic Blood Pressure
The Systolic Evaluation of Lotrel Efficacy and
Comparative Therapies Trial*
Reduction in Systolic Blood
Pressure (mm Hg)
0
Amlodipine Besylate
+ Benazepril HCl
(5+20 mg/day)
Amlodipine
Besylate
(10 mg/day)
Benazepril HCl
(40 mg/day)
-5
-10
-12.4
-15
-20
-21.1†
-25
*Ambulatory monitoring was used to measure blood pressure.
†P < 0.0001 for combination vs. amlodipine besylate alone and
combination vs. benazepril hydrochloride (HCl) alone.
Reprinted from Neutel JM, et al. J Clin Hypertens. 2005;
7:641-646, with permission from Blackwell Publishing.
-10.8
Incidence of Peripheral Edema:
The Systolic Evaluation of Lotrel Efficacy and
Comparative Therapies Trial*
10
9.4
Amlodipine Besylate
+Benazepril Hydrochloride
Patients (%)
8
5.6
6
4
Benazepril Hydrochloride
3.8
2
0
n = 6/149
Amlodipine Besylate
n = 15/146
*The data shown were derived from the expanded intentionto-treat population of the Systolic Evaluation of Lotrel Efficacy
and Comparative Therapies (SELECT) Trial.
Neutel JM, et al. J Clin Hypertens. 2005;7:641-646.
n = 9/161
Antihypertensive and Antiproteinuric
Responses to an Increasing Dose of an
Angiotensin-Converting Enzyme Inhibitor*
Lisinopril Dose
5 mg
10 mg
15 mg
20 mg
0
% Reduction
from Control
-10
-20
-30
-40
-50
-60
-70
-80
Blood Pressure
Urine Protein
*Subjects had normal blood pressures that would not be expected to
change much with angiotensin-converting enzyme inhibitor therapy. Similar findings have been shown with ARBs.
Palla R, et al. Int J Clin Pharmacol Res. 1994;14:35-43.
Recommendations in combination therapy
 Preferred
ACE inhibitor/diuretic∗
ARB/diuretic∗
ACE inhibitor/CCB∗
ARB/CCB∗
Acceptable
β-blocker/diuretic∗
CCB (dihydropyridine)/β-blocker
CCB/diuretic
Renin inhibitor/diuretic∗
Renin inhibitor/ARB∗
Thiazide diuretics/K+ sparing diuretics∗
 Less effective
ACE inhibitor/ARB
ACE inhibitor/β-blocker
ARB/β-blocker
CCB (nondihydropyridine)/β-blocker
Centrally acting agent/β-blocker
Summary
 Drugs from 11 major classes have been approved by the United




States Food and Drug Administration to treat hypertension
Many of these drugs have complementary effects to reduce blood
pressure and prevent target organ damage
The goal of antihypertensive therapy is to use doses of drugs that
effectively lower blood pressure while minimizing adverse effects
Combinations of drugs that have complementary actions – or allow
the actions of one drug to offset the adverse effects of a second
drug – are often required to achieve this goal
The dose-response relationship for a single drug may vary with the
target organ-protective effect for which that drug is being
prescribed
When and how to use self (home) and
ambulatory blood pressure monitoring
Thomas G. Pickering, MD, DPhil, William B. White, MD and American Society of Hypertension Writing Group
Journal of the American Society of Hypertension
Volume 2, Issue 3, Pages 119-124 (May 2008)
DOI: 10.1016/j.jash.2008.04.002
Copyright © 2008 American Society of Hypertension Terms and Conditions
Source: Journal of the American Society of Hypertension 2008; 2:119-124 (DOI:10.1016/j.jash.2008.04.002 )
Copyright © 2008 American Society of Hypertension Terms and Conditions
Cardiovascular Disease (CVD) in
Individuals with Diabetes
 CVD is a major cause of morbidity, mortality for
those with diabetes
 Common conditions coexisting with type 2 diabetes
(e.g., hypertension, dyslipidemia) are clear risk
factors for CVD
 Diabetes itself confers independent risk
 Benefits observed when individual cardiovascular
risk factors are controlled to prevent/slow CVD in
people with diabetes
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood Pressure
Control
Screening and diagnosis
 Measure blood pressure at every routine diabetes
visit
 If patients have systolic blood pressure
≥130 mmHg or diastolic blood pressure ≥80 mmHg
 Confirm blood pressure on a separate day
 Repeat systolic blood pressure ≥130 mmHg or diastolic
blood pressure ≥80 confirms a diagnosis of hypertension
(C)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood
Pressure Control
Goals
 A goal systolic blood pressure <130 mmHg is appropriate for
most patients with diabetes (C)
 Based on patient characteristics and response to therapy,
higher or lower systolic blood pressure targets may be
appropriate (B)
 Patients with diabetes should be treated to a diastolic blood
pressure <80 mmHg (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (1)
 Patients with a systolic blood pressure 130–139 mmHg
or a diastolic blood pressure 80–89 mmHg
 May be given lifestyle therapy alone for a maximum of 3
months
 If targets are not achieved, patients should be treated with the
addition of pharmacological agents (E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (2)
 Patients with more severe hypertension (systolic
blood pressure ≥140 mmHg or diastolic blood
pressure ≥90 mmHg) at diagnosis or follow-up
 Should receive pharmacologic therapy in addition to
lifestyle therapy (A)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (3)
 Lifestyle therapy for hypertension
 Weight loss if overweight
 DASH-style dietary pattern including reducing sodium,
increasing potassium intake
 Moderation of alcohol intake
 Increased physical activity (B)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (4)
 Pharmacologic therapy for patients with diabetes and hypertension
 Pair with a regimen that includes either an ACE inhibitor or angiotensin II
receptor blocker
 If one class is not tolerated, the other should be substituted
 If needed to achieve blood pressure targets
 Thiazide diuretic should be added to those with estimated GFR ≥30 ml x
min/1.73 m2
 Loop diuretic for those with an estimated GFR <30 ml x min/1.73 m2 (C)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations: Hypertension/Blood
Pressure Control
Treatment (5)
 Multiple drug therapy (two or more agents at maximal
doses)
 Generally required to achieve blood pressure targets (B)
 If ACE inhibitors, ARBs, or diuretics are used
 Kidney function, serum potassium levels should be monitored
(E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
Recommendations:
Hypertension/Blood Pressure Control
Treatment (6)
 In pregnant patients with diabetes and chronic
hypertension
 Blood pressure target goals of 110–129/65–79 mmHg are
suggested in interest of long-term maternal health and
minimizing impaired fetal growth
 ACE inhibitors, ARBs, contraindicated during pregnancy
(E)
ADA. VI. Prevention, Management of Complications. Diabetes Care 2011;34(suppl 1):S27.
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.
 No evidence to support HCTZ for use as first-line
therapy: Analysis published
 15 COMMENT S - JAN 25, 2011 15:15 EST
 New York, NY (updated) - The antihypertensive effect
of hydrochlorothiazide(HCTZ) at the dose that is most
often used—12.5 to 25 mg a day—is consistently inferior
to that of most other antihypertensive drug classes
when assessed on a 24-hour basis, a newly published
meta-analysis shows [1]. In addition, "there is no
evidence that HCTZ, at these doses, reduces heart
attack, stroke, or death," says lead author Dr Franz
Messerli (St Luke Roosevelt Hospital, New York, NY),
who with his colleagues reports their findings in the
February 1, 2011 issue of the Journal of
the American College ofCardiology. JACC.
Reference Card
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