Transcript Document

Practical Approaches to Managing
Hypertension: Reducing Global
Cardiovascular Risk
Randall M. Zusman, MD
Associate Professor of Medicine
Harvard Medical School
Director
Division of Hypertension and Vascular Medicine
Massachusetts General Hospital
Boston, Massachusetts
Key Question
Which class of agents do you presently
consider first-line treatment for patients
with hypertension?
1. Diuretics
2. β-Blockers (BBs)
3. Calcium channel blockers (CCBs)
4. Angiotensin-converting enzyme inhibitors (ACEIs)
5. Angiotensin receptor blockers (ARBs)
6. All of the above
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Faculty Disclosure
 Dr Zusman: advisory board member, research
support, speakers bureau: AstraZeneca, BristolMyers Squibb Company, Forest Pharmaceuticals,
Inc., Novartis Pharmaceuticals Corporation, Pfizer
Inc, sanofi-aventis Group, Sankyo Co., Ltd.
Learning Objectives
 State the prevalence of hypertension and its role
in the cardiovascular disease continuum
 Formulate hypertension management according
to risk stratification
 Describe the importance of targeting improvement
in vascular function in patients with hypertension
Hypertension and Global CV Risk
What Is Global CV Risk?
 Treating hypertension to goal is good
 Addressing all CV risk factors is better
 Achieve
optimal BP level
 Avoid CV and renal morbidity and mortality
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
JNC 7 Cardiovascular Risk Factors
 Hypertension
 Microalbuminuria
 Cigarette smoking
or estimated GFR
<60 mL/min
 Age (men >55 yr;
women >65 yr)
 Family history of
premature CVD
 Obesity (BMI ≥30 kg/m2)
 Physical inactivity
 Dyslipidemia
 Diabetes mellitus
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Key Question
What percentage of patients with hypertension
have 2 or more additional CV risk factors?
1. 20%
2. 30%
3. 40%
4. 50%
5. >50%
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CV Risk Factor Clustering With Hypertension:
Framingham Offspring, Aged 18 to 74 Years
>50% of Hypertension Occurs in Presence
of 2 or More Risk Factors
Men
Women
1 RF
2 RFs
1 RF
25%
26%
12%
3 RFs
4 or
More RFs
20%
17%
8%
No
Additional
RFs
24%
27%
22%
19%
2 RFs
No
Additional
RFs
RF = risk factor.
Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S.
3 RFs
4 or
More RFs
10-Year Probability of
Event (%)
Risk of CHD in Mild Hypertension by
Intensity of Associated Risk Factors
Risk Factors
40
42
36
30
21
24
18
10
12
6
4
14
6
0
SBP 150-160 mm Hg
TC 240-262 mg/dL
HDL-C 33-35 mg/dL
Diabetes
Cigarette smoking
ECG-LVH
+
−
−
−
−
−
+
+
−
−
−
−
+
+
+
−
−
−
Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S.
+
+
+
+
−
−
+
+
+
+
+
−
+
+
+
+
+
+
JNC 7: Algorithm for Hypertension
LIFESTYLE MODIFICATIONS
Not at Goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients
with diabetes or chronic kidney disease)
INITIAL DRUG CHOICES
Without Compelling Indications
Stage 1 Hypertension
Thiazide-type diuretics
for most; may consider
ACEI, ARB, BB, CCB,
or combo
Stage 2 Hypertension
2-drug combos for most
(usually thiazide-type
diuretics and ACEI,
or ARB, or BB, or CCB)
With Compelling Indications
Compelling Indications
Other drugs
(diuretic, ACEI, ARB,
BB, CCB) as needed
If not at goal BP, optimize dosages or add drugs until
goal BP achieved; consider consultation with hypertension specialist
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Nonpharmacologic Interventions
and BP Reduction
Weight Loss
(19.4 lb)
0
Low-Salt
Diet
Exercise
Alcohol
Potassium
Reduction Supplement
BP Decrease
(mm Hg)
1
2
3
4
5
6
SBP
DBP
7
Adapted from: Stevens VJ et al. Ann Intern Med. 2001;134:1-11; Messerli FH et al. In: Griffin BP et al,
eds. 2004. Manual of Cardiovascular Medicine. 2nd ed; Whelton SP et al. Ann Intern Med.
2002;136:493-503; Cutler JA et al. Am J Clin Nutr. 1997;65(suppl):643S-651S; Xin X et al. Hypertension.
2001;38:1112-1117; Whelton PK et al. JAMA. 1997;277:1624-1632.
JNC 7 Classification of Blood Pressure
STAGE 2
SBP 160 mm Hg or
DBP 100 mm Hg
Treatment
recommended
STAGE 1
SBP 140-159 mm Hg or
DBP 90-99 mm Hg
PREHYPERTENSION
SBP 120-139 mm Hg or
DBP 80-89 mm Hg
NORMAL
Consider treatment in
those with diabetes or
renal disease who fail
lifestyle modification
SBP <120 mm Hg and
DBP <80 mm Hg
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Goal BP Recommendations for Patients
With DM or Renal Disease
Organization
Year
Goal BP
(mm Hg)
Canadian Hypertension Society
2007
<130/80
American Diabetes Association
2006
<130/80
National Kidney Foundation
2004
<130/80
British Hypertension Society
2004
130/80
JNC 7
2003
<130/80
World Health Organization/
International Society of Hypertension
2003
<130/80
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
JNC 7: Compelling Indications
for Antihypertensive Drug Classes
Recommended Drugs
Compelling Indication
Heart failure
Post MI
High coronary
disease risk
Diabetes
Chronic kidney disease
Recurrent stroke
prevention
Diuretic ACEI
•
•
•
•
•
•
•
•
•
and
BB
•
•
Aldo
ARB CCB Ant
•
•
•
•
•
•
•
•
•
•
Aldo Ant = aldosterone antagonist.
Chobanian AV et al, for the NHBPEPCC. Bethesda, Md: NHLBI; 2004. NIH Publication No. 04-5230.
Available at: www.nhlbi.nih.gov/guidelines/hypertension/jnc7full.pdf.
Hypertension and Diabetes:
Global CV Risk Reduction With
Evidence-Based Intervention
Key Question
On average, how many drugs will a patient
need to control hypertension?
1. 1
2. 2
3. 3
4. 4
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Multiple Antihypertensive Agents
Needed to Achieve BP Goal: ALLHAT
1 Drug
2 Drugs
3 Drugs
% Controlled <140/90 mm Hg
100
Patients (%)
80
60
40
20
0
Baseline
6 Months
1 Year
3 Years
5 Years
Patients had hypertension and at least 1 other CHD risk factor. N = 33357.
Adapted from Cushman WC et al. J Clin Hypertens. 2002;4:393-404.
Multiple Antihypertensive Agents Needed to
Achieve BP Goal: Diabetes/Renal Impairment
UKPDS (<150/85 mm Hg)
MDRD (<92 mm Hg, MAP)
HOT (<80 mm Hg, diastolic)
AASK (<92 mm Hg, MAP)
RENAAL (<140/90 mm Hg)
IDNT (135/85 mm Hg)
1
2
3
Average No. of BP Medications
Patients had either diabetes or renal impairment.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661; Brenner BM et al. N Engl J Med. 2001;345:861869; Lewis EJ et al. N Engl J Med. 2001;345:851-860.
4
DM Approximately Doubles CVD Risk
in Patients With Hypertension
Study
Patients With Patients Without
Diabetes
Diabetes
(events per 1000 pt-yr)
Ratio
SHEP
CV events
63.0
36.8
1.71
Stroke
28.8
15.0
1.92
CHD events
32.2
15.2
2.12
CV events
55.0
28.9
1.90
Stroke
26.6
12.3
2.16
CHD events
23.1
12.4
1.87
24.0
9.8
2.45
Syst-Eur
HOT (DBP <90 mm Hg)
CV events
Adapted from Curb JD et al. JAMA. 1996;276:1886-1892; Hansson L et al. Lancet. 1998;351:1755-1762;
Tuomilehto J et al. N Engl J Med. 1999:340:677-684.
HOT Study: Fewer Major CV Events in Patients
With Diabetes Randomized to Lower BP Goal
P = .005
(per 1000 patient-years)
Stroke, MI, or CV Death
25
20
15
10
5
0
80
85
90
Target DBP (mm Hg)
Patients with hypertension and diabetes were given baseline felodipine, plus other agents
in a 5-step regimen. Study N = 18790; diabetes n = 1501.
HOT = Hypertension Optimal Treatment; MI = myocardial infarction.
Adapted from Hansson L et al, for the HOT Study Group. Lancet. 1998;351:1755-1762.
Syst-Eur: CV Protection Resulting From BP
Lowering Was Greatest in Patients With Diabetes
Reduction in Event Rate for
Active Treatment Group (%)
With Diabetes
0
–10
–20
Overall
Mortality
8%
P = .55
–30
–40
–50
Without Diabetes
All CV
CVD
Events
Mortality
16%
P = .37
41%
P = .09
–60
–70
25%
P = .02
70%
P = .01
62%
P = .002
Fatal and
Nonfatal
Stroke
36%
P = .02
69%
P = .02
Fatal and
Nonfatal
Cardiac Events
22%
P = .10
57%
P = .06
Patients with hypertension received nitrendipine  enalapril or HCTZ. N = 4695.
Syst-Eur = Systolic Hypertension in Europe; CV = cardiovascular.
Adapted from Tuomilehto J et al. N Engl J Med. 1999;340:677-684.
UKPDS: Tight Glucose Versus Tight
BP Control and CV Outcomes
Tight glucose control (goal <6.0 mmol/L or 108 mg/dL)
Tight BP control (average 144/82 mm Hg)
Relative Risk Reduction (%)
Stroke
Any Diabetic
Endpoint
DM
Deaths
Microvascular
Complications
0
-10
5%
10%
12%
-20
24%
*
-30
32%
*
-40
-50
44%
*
32%
*P <.05 compared to tight glucose control
Patients had hypertension and type 2 diabetes. N = 1148.
Bakris GL et al. Am J Kidney Dis. 2000;36:646-661.
37%
*
Currently Available Antihypertensive
Medications: Mechanism of Action
Drug Class
Mechanism of Action
 Rid the body of excess fluids and sodium
Diuretics
through urination
 May enhance the effect of other BP medications
ACEIs
 Lower levels of angiotensin II
 Expand blood vessels
ARBs
 Block angiotensin II receptors
 Expand blood vessels
BBs
 Decrease heart rate and cardiac output
CCBs
 Interrupt movement of calcium into heart and
vessel cells
American Heart Association. December 11, 2006. Available at:
http://americanheart.org/presenter.jhtml?identifier=159.
The Renin-Angiotensin-Aldosterone
System (RAAS)
Angiotensinogen
Kininogen
Kallikrein
Nitric
Oxide
Renin
ACEIs
Bradykinin
Inactive Peptides


Angiotensin I
ACE
Angiotensin II

 Blood Pressure
 Vascular Proliferation
 Oxidative Stress
 Vascular Inflammation
 Thrombogenesis
ACEI
AT1
ARB
Adapted with permission from Brown NJ et al. Circulation. 1998;97:1411-1420.
Endemann DH. J Am Soc Nephrol. 2004;15:1983-1992.
ARBs
ARBs
The Renin-Angiotensin-Aldosterone
System (RAAS)
Angiotensinogen
Kininogen
Renin
Inhibitors
Renin 
Kallikrein
Bradykinin
Angiotensin I
ACE
Inactive Peptides
Angiotensin II
ARBs
 Blood Pressure
 Vascular Proliferation
 Oxidative Stress
 Vascular Inflammation
 Thrombogenesis
AT1
Adapted with permission from Brown NJ et al. Circulation. 1998;97:1411-1420; Endemann DH.
J Am Soc Nephrol. 2004;15:1983-1992.
VALUE: Hazard Ratios for Prespecified Analyses
in Patients With Hypertension at High CV Risk
Hazard Ratio
Valsartan/Amlodipine
Primary cardiac composite endpoint
Cardiac mortality
Cardiac morbidity
All myocardial infarction
All congestive heart failure
All stroke
All-cause death
New-onset diabetes
0.5
1
Favors Valsartan
2.0
Favors Amlodipine
Patients had hypertension and were at high CV risk.
VALUE = Valsartan Antihypertensive Long-term Use Evaluation.
Julius S et al, for the VALUE trial group. Lancet. 2004;363:2022-2031.
Event-Free Probability (%)
Val-HeFT: HF Morbidity With ARB
in Patients Not Receiving ACEIs
100
Valsartan (n = 185)
Placebo (n = 181)
80
60
40
Risk Reduction 44%
(P <.001)
20
0
0
3
6
9
12
15
Months
18
21
24
ACEI = angiotensin-converting enzyme inhibitor; ARB = angiotensin receptor
blocker; HF = heart failure.
Maggioni AP et al. J Am Coll Cardiol. 2002;40:1414-1421.
27
VALIANT:
ARBs in Secondary Prevention
All-Cause Mortality
(probability)
Acute dual RAS blockade provides no significant benefit
0.4
Captopril
0.3
Valsartan
Valsartan and captopril
0.2
0.1
Valsartan vs captopril: HR = 1.00; P = .982
Valsartan + captopril vs captopril: HR = 0.98; P = .726
0.0
0
6
12
18
24
30
36
Months
Patients had post-MI HF or LVSD (EF <0.40). N = 14703.
EF = ejection fraction; LVSD = left ventricular systolic dysfunction; MI = myocardial
infarction; RAS = renin-angiotensin system; VALIANT = Valsartan in Acute Myocardial
Infarction Trial.
Pfeffer M et al. N Engl J Med. 2003;349:1893-1906.
All-Cause Mortality (%)
COMET: Primary Endpoint of Mortality
40
Metoprolol
Carvedilol
30
20
HR = 0.83
95% CI, 0.74-0.93
P = .0017
10
0
0
1
2
3
Time (years)
Carvedilol n = 1511; metoprolol n = 1518.
COMET = Carvedilol or Metoprolol European Trial.
Poole-Wilson PA et al. Lancet. 2003;362:7-13.
4
5
OR (95% CL) for the
Occurrence of MI
ACEI Versus Placebo: Effect on MI
1.5
1.0
0.7
0.5
1.3
3.0
3.1
Years
Patients had HF and/or LVD.
Strauss MD, Hall A. Circulation. 2006;114:838-854.
3.4
3.5
EUROPA: CV Death/MI/Cardiac Arrest
Placebo
20% Risk Reduction
HR = 0.80 (0.71–0.91)
P = .0003
Perindopril
8 mg
Time (years)
Percent
15
10
5
Time (years)
0
0
30
25
20
15
10
5
0
HOPE: CV Death/MI/Stroke
Placebo
22% Risk Reduction
HR = 0.78 (0.70–0.86)
Ramipril
P <.001
10 mg
20
Percent
14
12
10
8
6
4
2
0
1
2
3
4
5
0
PEACE: CV Death/MI/CABG/PCI
4% Risk Reduction Placebo
HR = 0.96 (0.88–1.06)
P = .43
Trandolapril
4 mg
Time (years)
1
2
3
4
5
6
1
2
3
QUIET: All CV Events
4% Risk Increase
HR = 1.04 (0.89–1.22)
P = .6
50
Percent
Percent
ACEI Trials in CAD Without HF:
Primary Outcomes
40
30
4
Quinapril
20 mg
Placebo
20
10
Time (years)
0
0
1
2
EUROPA Investigators. Lancet. 2003;362:782-788; HOPE Study Investigators. N Engl J Med.
2000;342:145-153; PEACE Trial Investigators. N Engl J Med. 2004;351:2058-2068; Pitt B, et al.
Am J Cardiol. 2001;87:1058-1063.
3
Primary Outcome (%)
MICRO-HOPE, PERSUADE:
CV Events in Patients With Diabetes
MICRO-HOPE
(n = 3577)
CV death/MI/stroke
25
25
PERSUADE
(n = 1502)
CV death/MI/cardiac arrest
Placebo
20
Placebo
20
25% RRR
P = .0004
15
19% RRR
P = .13
15
10
5
Perindopril
8 mg
10
Ramipril
10 mg
5
0
0
0
1
2
3
4
Follow-Up (years)
5
0
1
2
3
4
Follow-Up (years)
5
HOPE Study Investigators. Lancet. 2000;355:253-259; Daly CA et al. Eur Heart J. 2005;26:1369-1378.
MICRO-HOPE: Albuminuria in Patients
With Diabetes
Mean Albumin/Creatinine
Ratio (urine)
3.0
Placebo
2.5
Ramipril
2.0
P = .02
1.5
P = .001
1.0
0.5
0.0
0
1
2
Time (y)
HOPE Study Investigators. Lancet. 2000;355:253-259.
3
4-5
The Data Support Global CV
Risk Management
 CV disease remains the leading cause of death
in both men and women in the United States
 Framingham data show that CV risk factors tend to
cluster—and that risk of death from CHD and stroke
increases proportionately
 Endothelial dysfunction seems to be a key factor
in the development of CV disease
 Recent clinical trials have given us a wealth of
information with which to manage global CV risk
Adherence
CV Risk Factor Control Among Adults
With Diagnosed Diabetes
Fewer than half of adults with diabetes achieve
treatment goals for CV risk factors
NHANES III (n = 1204)
NHANES 1999-2000 (n = 370)
60
Adults (%)
50
40
48.2
44.3
37.0
35.8
33.9
29.0
30
20
10
0
5.2
A1C Level
<7%
7.3
Blood Pressure Total Cholesterol* Achieved All 3
<130/80 mm Hg
<200 mg/dL
Treatment Goals
*LDL-C and TG not evaluated.
Saydah SH, et al. JAMA. 2004;291:335-342.
Practical Tips to Improve Adherence
 Talk to your patient






Explain the condition and why specific therapy is important
Ask about adherence
Involve the patient as a partner in treatment
Provide clear written and oral instructions
Tailor the regimen to the patient’s lifestyle and needs
Use motivational interviewing techniques
 Look for:
 Different ways to approach patients based on individual
patient attitudes
 Allies in patient care—family, friends
 Ways to simplify the regimen
 Refill dates (if the patient has not refilled the prescription,
the medication is not being taken)
Ockene IS et al. J Am Coll Cardiol. 2002;40:630-640.
Practical Tips to Improve Adherence
 Use systematic approaches


Disease management programs
Periodic review of electronic medical records or manual
chart audits
 Group/shared medical appointments—blend care, education,
social support
 Other techniques
 Follow-up (telephone/mail/e-mail) and reminder cards
 Signed agreements/contracts
 Self-monitoring tools (eg, tape measure, pedometer,
home testing devices)
 Patient assistance programs
 Support patients where medication costs are a barrier
to adherence
Fonarow GC et al. Am J Cardiol. 2001;87:819-822; Ockene IS et al. J Am Coll Cardiol. 2002;40:
630-640; NCEP ATP III. September 2002. NIH publication no. 02-5215;
Pfizer Helpful Answers Web site. Available at: http://www.pfizerhelpfulanswers.com.
Case Study
Case Study: 55-Year-Old Asian Man
With Hypertension and Type 2 Diabetes
 Physical examination






BP: 148/96 mm Hg
Height: 64"
Weight: 178 lb
BMI: 30 kg/m2
Waist circumference: 38"
Cardiac dysfunction status:
normal ventricular function
(LVEF 68%)
 Laboratory values

Glucose: 148 mg/dL
(fasting)
 A1C: 8.8%
 Creatinine: 1.5 mg/dL
 Urinalysis: 1+ proteinuria
 Lipid profile (mg/dL):
TC: 268; LDL-C: 168;
HDL-C: 42; TG: 296
 Medications
 HCTZ 25 mg/d
 Glyburide 5 mg/d
Decision Point
What is the JNC 7 goal for this patient who has
hypertension, diabetes, and renal disease?
1. <120/80 mm Hg
2. <130/80 mm Hg
3. <140/80 mm Hg
4. <140/90 mm Hg
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Decision Point
The patient’s BP is 148/96 mm Hg while
taking HCTZ 25 mg/d and glyburide 5 mg/d.
To bring BP down to <130/80 mm Hg, you would
add a(n):
1. BB
2. CCB
3. ARB
4. ACE
Use your keypad to vote now!
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Q&A
PCE Takeaways
PCE Takeaways
1. Patients with hypertension often present with
multiple cardiac risk factors
2. Be vigilant in your investigation of all clinical
indicators
3. Creatively address patient adherence; not
everyone responds to the same interventions
4. Clinical inertia is the enemy—don't settle for
"close enough"
Key Question
How important is using an antihypertensive agent
with proven risk reduction (reducing morbidity
and mortality) when choosing medications for
your patients with hypertension?
1. Not important
2. Slightly important
3. Somewhat important
4. Extremely important
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