Transcript Improving Treatment and Control - Heart Disease Prevention Program

1
Improving Blood Pressure Treatment
in the Community: Implications of the
JNC7 Recommendations and ALLHAT
Results
Nathan D. Wong, PhD, FACC
Professor and Director
Heart Disease Prevention Program
University of California, Irvine
2
Hypertension: A Significant CV and
Renal Disease Risk Factor
CAD
CHF
LVH
Stroke
Hypertension

Morbidity
Renal
disease
Peripheral
vascular disease

Disability
National High Blood Pressure Education Program Working Group. Arch Intern Med. 1993;153:186208.
3
Hypertension:
How Big Is the Problem?
At Least 65 Million Americans Require
Treatment for Hypertension
Nearly 1 in 3 adults (31%) in the US has hypertension
Fields LE et al. Hypertension. 2004;44:398-404.
4
Risk of Cardiovascular Events
by Hypertensive Status
36-Year Follow-up in Patients Aged 35-64
Years
Biennial Age-Adjusted Rate
per 1,000
50
Coronary Disease
45.4
Peripheral Arterial
Disease
Stroke
Cardiac Failure
40
Normotensive
Hypertensive
30
22.7
21.3
20
13.9
12.4
9.9
9.5
10
6.2
3.3
2.4
7.3
5.0
2.0
6.3
3.5
2.1
0
Men
Women
Men
Women
Men
Women
Reprinted with permission from Kannel WB. JAMA. 1996;275:1571-1576.
Men
Women
5
SBP-Associated Risks: MRFIT
SBP versus DBP in Risk of CHD Mortality
CHD Death Rate
100+
90–99
80–89
Diastolic BP 75–7970–74
(mm Hg)
160+
140–159
120–139
<70
<120
Systolic BP
(mm Hg)
Adapted from Neaton JD et al. Arch Intern Med. 1992;152:56-64.
Distribution of Hypertension Subtype in the untreated
Hypertensive Population in NHANES III by Age
ISH (SBP 140 mm Hg and DBP <90 mm Hg)
SDH (SBP 140 mm Hg and DBP 90 mm Hg)
IDH (SBP <140 mm Hg and DBP 90 mm Hg)
100
17%
16%
<40
40-49
16%
20%
20%
11%
50-59 60-69
Age (y)
70-79
80+
80
Frequency of
hypertension 60
subtypes in all
untreated
40
hypertensives
(%)
20
0
Numbers at top of bars represent the overall percentage distribution of untreated hypertension by
age.
Franklin et al. Hypertension 2001;37: 869-874.
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Elevated SBP Alone Is Associated With
Increased Risk of Cardiovascular and Renal
Disease
Disease
Kidney failure (ESRD)
Stroke
Heart failure
Peripheral vascular disease
Myocardial infarction*
Coronary artery disease
Relative Risk
2.8
2.7
1.5
1.8
=1.6
1.5
ESRD = end-stage renal disease; SBP 165 mm Hg.
*Men only.
Adapted from Kannel WB. Am J Hypertens. 2000;13:3S-10S; Perry HM Jr et al. Hypertension. 1995;25(part
1):587-594;
Klag MJ et al. N Engl J Med. 1996;334:13-18; Nielsen WB et al. Ugeskr Laeger. 1996;158:3779-3783; Neaton
JD et al.
Arch Intern Med. 1992;152:56-64.
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9
Prevalence, Awareness, Treatment, and Control
of Hypertension in US Adults 2003-2004
(Ong et al., Hypertension 2007; 49: 69-75)
60
Percent (%)
50
58
53.7
52.1
48.3
40
30
55
30.7
35.4
35.2
33.3
28.2
28.5
39.1
28.9
27.8 26.5
20
10
0
Men
Women
Prevalence
White
Black
Treatment
Control
Hispanic
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Prevalence (%) of HTN in US Adults, by Disease Status
(Wong et al, Arch Intern Med 2007, in press)
Prevalence of HTN (%)
100
**
76.8
80
**
51.8
60
40
**
81.8
**
61.5
** **
**
69.5 71.4 73.7
**
73
23.1
20
0
Mean age (y):
53.5
No-Disease
59.3
Dyslipidemia
54.8 60.5
Mets
DM
**P<0.01 when compared to No-Disease Group
76.1 65.9 68.2 69.3 67.2
CKD
Stroke
CHF
PAD
CAD
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Treatment (%) of HTN in US Adults, by Disease Status
(Wong et al., Arch Intern Med 2007, in press)
Treatment of HTN (%)
100
80
**
89
**
84
66.5
68
70.9
**
89.3
**
83.4
73.4
65.9
60
40
20
0
No-Disease
Dyslipidemia
Mets
DM
*P<0.05, **P<0.01 when compared to No-Disease group
Treatment is in persons with HTN
CKD
Stroke
CHF
PAD
CAD
12
Control (all treated) (%) of HTN in US Adults, by Disease
Status (Wong et al., Arch Intern Med 2007, in press)
Control of HTN (%)
100
80
60
64.6
*
63.7 61.2
49.3
48.8
**
42.2
40
**
**
46.7 50.3
34.9
20
0
No-Disease
Dyslipidemia
Mets
DM
CKD
Stroke
**P<0.05**P<0.01 when compared to No-Disease Group
Control is in persons with HTN defined as BP < 140/90
If DM and CKD is based on BP<130/80 control is **35.3% and **23.2%, respectively.
If MetS is based on BP<130/85 control is **46.7%
CHF
PAD
CAD
13
Mean BP and Distance to Goal Among HTN Pts Not at Goal
(Wong et al., Arch Intern Med 2007, in press)
SBP mm Hg
(Distance to
Goal)
DBP mm Hg
(Distance
to Goal)
No Disease
154 (14)
93
(3)
Dyslipidemia
154 (19)
90* (7)
MetS
154 (16)
94
DM
149* (14)
87** (6)
CKD
155 (18)
87** (7**)
Stroke
155 (22*)
87** (6)
CHF
154 (22**)
89** (6)
PAD
157 (23**)
89* (7)
CAD
155 (21*)
90
(5)
(6)
Minimum BP distance from goal of < 140/90 in parenthesis, even with DM & CKD
*p<0.05 **p<0.01 compared to no disease
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Blood Pressure Classification
BP Classification
SBP mmHg
DBP mmHg
Normal
Prehypertension
<120
120–139
and
or
<80
80–89
Stage 1 HTN
140–159
or
90–99
Stage 2 HTN
>160
or
>100
15
4-Year Progression To Hypertension:
The Framingham Heart Study
Participants age 36 and older
50
37
Patients (%)
40
30
18
20
10
5
0
Optimal
Normal
(<120/80 mm
(130/85 mm
Hg)
Hg)
Vasan, et al. Lancet 2001;358:1682-86
High-Normal
(130-139/85-89 mm
Hg)
HOT Study: Significant Benefit From
Intensive Treatment in the Diabetic Subgroup
25
20
Major
cardiovascul 15
ar
events/1,00
0 patient- 10
years
p=0.005 for trend
5
0
90
85
Target Diastolic Blood Pressure
Hansson L et al. Lancet. 1998;351:1755-1762.
80
mm Hg
17
Benefits of Lowering BP
Average Percent Reduction
Stroke incidence
35–40%
Myocardial infarction
20–25%
Heart failure
50%
TROPHY Study ACC 2006: Even lowering BP in those with preHTN appears to reduce incidence of new HTN by up to 60%
18
19
Preventable CHD Events from Control of
Hypertension in US Adults
(Wong et al., Am Heart J 2003; 145: 888-95)
56
60
PAR% / NNT
50
39
37
40
31
30
20
21
21
19
11
10
0
Men PAR%
Women PAR%
Treatment to <140/90 mmHg
Men
NNT
Women NNT
Treatment to <120/80 mmHg
PAR% = population attributable risk (proportion of CHD events preventable), NNT
= number needed to treat to prevent 1 CHD event ; <0.01 comparing men and
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Randomized Design
of ALLHAT
ALLHAT
High-risk
hypertensive
patients
Consent /
Randomize
(42,418)
Eligible for lipidlowering
Amlodipine
Chlorthalidone
Doxazosin
Lisinopril
Not eligible for
lipid-lowering
Consent / Randomize (10,355)
Pravastatin
Usual care
Follow for CHD and other outcomes until death or end of study (up to 8 yr).
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ALLHAT
Baseline Characteristics
and Follow-up
Baseline
Follow-up
N
42,418
Known alive
82%
Mean SBP/DBP
146 / 84
Confirmed dead
15%
Mean age, y
67
Lost / refused
3%
Black, %
36
99%
Women, %
47
Person-years
(% obs/exp)
Current smoking %
22
History of CHD, %
26
Type 2 diabetes, %
36
On antihypertensive treatment, %
92
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ALLHAT
Doxazosin Arm
Terminated Early
• Futility of finding a significant difference
for primary CHD outcome
• Statistically significant 20 percent higher
rate of major secondary endpoint,
combined CVD outcomes (80% higher rate
of heart failure)
Hypertension. 2003;42:239-246.
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ALLHAT BP Results by Treatment Group
Amlodipine
Lisinopril
150
90
145
85
mm Hg BP
mm Hg BP
Chlorthalidone
140
80
135
75
130
70
0
1
2
3
Years
4
5
6
0
1
2
3
Years
4
5
Compared to chlorthalidone:
Compared to chlorthalidone:
SBP significantly higher in the
amlodipine group (~1 mm Hg) and
the lisinopril group (~2 mm Hg).
DBP significantly lower in the
amlodipine group (~1 mm Hg),
similar in the lisinopril group.
6
24
ALLHAT
Cumulative Event Rates for the Primary
Outcome (Fatal CHD or Nonfatal MI) by
ALLHAT Treatment Group
Cumulative CHD Event Rate
.2
.16
RR (95% CI)
p value
A/C
0.98 (0.90-1.07)
0.65
L/C
0.99 (0.91-1.08)
0.81
Chlorthalidone
Amlodipine
Lisinopril
.12
.08
.04
0
0
Number at Risk:
Chlorthalidone
Amlodipine
Lisinopril
15,255
9,048
9,054
1
14,477
8,576
8,535
2
13,820
8,218
8,123
3
4
Years to CHD Event
13,102
7,843
7,711
11,362
6,824
6,662
5
6,340
3,870
3,832
6
2,956
1,878
1,770
7
209
215
195
25
ALLHAT
Subgroup Comparisons
Results were consistent across age, race,
gender, and baseline diabetes subgroups,
except:
– Stroke
• Black L/C RR (95% CI) = 1.40 (1.17 – 1.68)
• Non-Black L/C RR (95% CI) = 1.00 (0.85 – 1.17)
– Combined CVD
• Black L/C RR (95% CI) = 1.19 (1.09 – 1.30)
• Non-Black L/C RR (95% CI) = 1.06 (1.00 – 1.13)
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Nonfatal MI + CHD Death – Subgroup
Comparisons – RR (95% CI)
ALLHAT
Total
0.98 (0.90, 1.07)
Total
0.99 (0.91, 1.08)
Age <65
0.99 (0.85, 1.16)
Age < 65
0.95 (0.81, 1.12)
Age>=65
0.97 (0.88, 1.08)
Age >= 65
1.01 (0.91, 1.12)
Men
0.98 (0.87, 1.09)
Men
0.94 (0.85, 1.05)
Women
0.99 (0.85, 1.15)
Women
1.06 (0.92, 1.23)
Black
1.01 (0.86, 1.18)
Black
1.10 (0.94, 1.28)
Non-Black
0.97 (0.87, 1.08)
Non-Black
0.94 (0.85, 1.05)
Diabetic
0.99 (0.87, 1.13)
Diabetic
1.00 (0.87, 1.14)
0.97 (0.86, 1.09)
Non-Diabetic
0.99 (0.88, 1.11)
Non-Diabetic
0.50
Amlodipine Better
1
2
Chlorthalidone Better
0.50
Lisinopril Better
1
2
Chlorthalidone Better
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Predicted Cause-specific Mortality
for 2 mm Hg lower SBP
CHD
Stroke
Heart failure
-4 to -7%
-4 to -10%
-5 to -7%
Higher numbers for younger
hypertensives
Prospective Studies Collaboration, Lancet 2002;360:1903-13
Summary of Outcomes
Relative Risks and 95% CI
ALLHAT
Amlodipine / Chlorthalidone
Lisinopril / Chlorthalidone
CHD
0.98 (0.91, 1.08)
0.99 (0.91, 1.08)
Death
0.96 (0.89, 1.02)
1.00 (0.94, 1.08)
CCHD
1.00 (0.94, 1.07)
1.05 (0.98, 1.11)
Stroke
0.93 (0.82, 1.06)
1.15 (1.02, 1.30)
CCVD
1.04 (0.99, 1.09)
1.10 (1.05, 1.16)
HF
1.38 (1.25, 1.52)
1.19 (1.07, 1.31)
0.50
Amlodipine
Better
1
2
Chlorthalidone
Better
0.50
Lisinopril
Better
1
2
Chlorthalidone
Better
28
29
ALLHAT
Fasting Glucose Results
Chlorthalidone
Amlodipine
Lisinopril
Serum fasting glucose – mmol/L, mean (sd)
Among baseline nondiabetics with baseline <126 mg/dL – mean (SD)
Baseline
4 Years
93.1 (11.7)
93.0 (11.4)
93.3 (11.8)
104.4 (28.5)
103.1 (27.7)
100.5 (19.5)*
Diabetes Incidence (follow-up fasting glucose  126 mg/dL)
4 Years
* p<.05 compared to chlorthalidone
11.6%
9.8%*
8.1%*
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ALLHAT
ALLHAT Results by Baseline
Diabetic Status
• Outcome results were similar in diabetic and
nondiabetic participants
• For both diabetic and nondiabetic participants,
there were significant advantages for the
diuretic arm
31
ALLHAT
Effect of 2-Year Changes in Fasting Glucose on ALLHAT
Endpoints
(Cox Regressions Beginning at 2 Years)
Per 10-Unit of Increase in Fasting Glucose (Baseline to
2 Years)
Endpoint
Hazard Ratio
95% CI
P
CHD
1.022
0.979 – 1.066
0.327
CCHD
1.004
0.968 – 1.042
0.824
Stroke
0.986
0.909 – 1.069
0.727
CCVD
1.003
0.971 – 1.036
0.836
Heart failure
1.000
0.939 – 1.066
0.988
ESRD
1.035
0.921 – 1.164
0.561
Total mortality
0.990
0.948 – 1.035
0.664
32
Diuretics, Potassium,
and Glucose
• Based on 40+ years’ evidence, potassium depletion
is a major factor relating thiazide treatment and
abnormal glucose.
• Both reduced insulin release and decreased insulin
sensitivity have been demonstrated.
• More attention than is often given to preventing or
reversing hypokalemia is warranted, especially in
patients at risk of diabetes.
Reference: Wilcox CS. Seminars in Nephrology, 1999;19:557-68.
33
Large Hypertension Trials Comparing Two or More
Regimens: CVD or CV Mortality
Trial
n
BPΔ
CAPPP
10,985
+3/+1
captopril not superior to D/BB
NORDIL
10,881
+3/0
diltiazem not superior to D/BB
CONVINCE
16,602
0/+1
verapamil not superior to D/BB
6,628
0/-1
isradipine/felodipine &
STOP-2
Outcomes
0/0
ACEIs not superior to D/BB
nifed GITS not superior to diuretic
INSIGHT
6,592
0/0
LIFE
9,193
+1/0
losartan superior to atenolol
ANBP-2
6,083
+1/0
ACEIs not superior to diuretics
ALLHAT
42,418
-3/-1
chlorthalidone superior to doxazosin,
-1/+1,-2/ 0
INVEST
22,576
0/ 0
amlodipine (HF only), lisinopril
verapamil (+trandolapril) equivalent
to atenolol (+HCTZ)
VALUE
15,313
+2/+2
valsartan not superior to amlodipine
34
35
36
Large, controlled trials have shown similar
mortality or morbidity reductions with:
Bendrofluazide (MRC)
Chlorthalidone (SHEP, HDFP)
Hydrochlorothiazide (VA, Oslo, Australian)
Indapamide (PATS, PROGRESS)
HCTZ/amiloride (MRC-O, STOP-H)
HCTZ/triamterene (EWPHE)
Conclusion
Independent trial findings support the view
that all thiazide diuretics are beneficial
37
ACEIs and ARBs Reduce
Cardiovascular Morbidity and
Mortality
ACEIs
Relative Risk Reduction, %
SOLVD
Placebo (n=1284)
Enalapril (n=1285)
CONSENSUS
Placebo (n=126)
Enalapril (n=127)
ARBs
HOPE
Placebo (n=4652)
Ramipril (n=4645)
LIFE
Val-Heft
CHARM-Added
Atenolol (n=4588) Valsartan (n=2511) Placebo (n=1272)
Losartan (n=4605) Placebo (n=2499) Candesartan (n=1276)
0
–10
–20
–30
–40
Mortality in
chronic HF
Total mortality
in severe HF
MI, stroke,
or CV death
in high-risk
patients
Death, MI,
or stroke in
patients aged
55–80 years
with
hypertension
and LVH
All cause
mortality and
morbidity
in patients
with HF
CV death
or HF
hospitalization
in patients
with chronic HF
angiotensin-converting enzyme inhibitors (ACEI); angiotensin receptor blocker (ARB); myocardial infarction (MI);
cardiovascular (CV); heart failure (HF); left ventricular hypertrophy (LVH).
Yusuf S et al. N Engl J Med. 2000;342:145-153; The CONSENSUS Trial Study Group. N Engl J Med. 1987;316:1429-1435;
The SOLVD Investigators. N Engl J Med. 1991;325:293-302; Granger CB et al. Lancet. 2003;362:772-776; Dahlof B et al.
Lancet. 2002;359:995-1003; Cohn JN et al. N Eng J Med. 2001;345:1667-1675.
38
Implications for Your Practice
and Your Patients
•
The blood pressure goal for most patients with
hypertension is <140/90 mm Hg.
•
Initial drug therapy for most should be either
thiazide-type diuretic alone or combined with
other drug classes.
•
Most patients with uncontrolled Stage 1 or Stage
2 hypertension should experience better blood
pressure control and better long term CVD risk
when the medication regimen includes a
thiazide-type diuretic.
39
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.
40
AHA Scientific Statement Recommendations:
General CVD Prevention, High CAD Risk, Stable and
Unstable Angina, NSTEMI, STEMI, LVD
(Circulation 2007; 115: 2761-2788)
41
AHA 2007 Statement Recommendations
• A target BP of <130/80 mmHg is
reasonable for individuals with any of the
following (Class IIa, level of evidence B):
–
–
–
–
–
–
–
–
Diabetes mellitus
Chronic renal disease
Coronary artery disease (CAD)
CAD risk equivalents
Carotid artery disease
Peripheral artery disease
Abdominal aortic aneurysms
High risk pts defined as >=10% 10-year risk
from FRS
42
Compelling Indications for
Individual Drug Classes
Compelling Indication
Initial Therapy Option
Heart failure
THIAZ, BB, ACEI, ARB,
ALDO ANT
Post myocardial
infarction
High CAD Risk
BB, ACEI, ALDO ANT
Diabetes
THIAZ, BB, ACEI, ARB,
CCB
ACEI, ARB
Chronic kidney disease
Recurrent stroke
prevention
THIAZ, BB, ACEI, CCB
THIAZ, ACEI
Renin Inhibition With
Aliskiren
Binding of Angiotensinogen
Prevented
43
•
Angiotensinogen
Rahuel J et al. J Struct Biol. 1991;107:227-236.
Aliskiren binds to a pocket
in the renin molecule,
blocking angiotensinogen
from being cleaved by renin
44
Aliskiren Suppresses the
Entire System—Targets the
Point of Activation
(Pro)Renin Receptor
Actions:
• Binding of (Pro)Renin
• Increased renin
catalytic activity
• Activates VSMC ERK1/2
Aliskiren
Angiotensinogen
Renin
Ang I
Non-ACE
pathways
Aliskiren
Heart
Kidney
Ang II
Vessels
 Vasoconstriction
 Remodelling
ACEIs
(Pro)Renin
receptor
Target cell
ARBs
ACE
Aldosterone
Ang III + IV
AT1 receptor
renin-angiotensin-aldosterone system (RAAS); vascular smooth muscle cells (VSMC); extracellular singal-regulated
kinases (ERK 1/2); angiotensin (Ang); angiotensin-converting enzyme (ACE); angiotensin-converting enzyme inhibitor
(ACEI); angiotensin receptor blockers (ARB); type 1 angiotensin II receptor (AT 1) .
45
Lifestyle Modifications
•
Most patients will experience better control if they modify
diet and exercise.
•
Physician advice sometimes works and should always be
given along with a follow-up visit appointment to monitor
both blood pressure and lifestyle change efforts.
•
Most of us do not do lifestyle counseling beyond simple
advice and admonishment – the time factor is a problem.
•
Nevertheless, lifestyle modification is at the top of the
JNC7 algorithm.
46
47
Lifestyle Modification
Modification
Approximate SBP
reduction (range)
Weight reduction
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
48
The Japanese Diet and Lifestyle
49
Keys to Physician Influence
in Lifestyle Modification
•
Advice giving and follow-up monitoring
are a minimum (many pts are not
adequately titrated to goal BP)
•
Some evidence that brief behavioral
counseling aimed at matching messages
to patient readiness to change and
eliciting the patient’s own motivation to
change can move the patient along a
continuum of change
50
Physician Influence in Lifestyle
Modification- What to Do
PICM
• Permission: Ask the patient for permission to talk
about lifestyle change and get preference for beginning with
diet or exercise
• Interest: Ask the patient about readiness to change – How
interested are you on a scale of 1-10. Ask why they are not a
lower number – to elicit a motivational statement from the
patient.
• Confidence: Ask how sure they are that they can do the
behavior – again ask why not a lower number
• Match a message to interest and confidence
51
Summary: For better long-term CVD
risk for your patients
• Focus on blood pressure control for both
SBP and DBP (<140/90 mm Hg - <130/80 for
patients with diabetes or chronic renal
disease)
• Follow the JNC7 treatment guidelines: Use a
thiazide-type diuretic as first line treatment
and in combination for uncontrolled HTN
• Do your part to disseminate these evidencebased guidelines
• Make a renewed effort to encourage lifestyle
change
52
Tools to Enhance BP Control
For use with patients:
• Physician-patient hypertension treatment planning pad for
exam rooms
• Poster for exam rooms
• The DASH Eating Plan (also on CD & NHLBI.ORG)
• Brief behavioral counseling steps and patient monitoring
tools
For your reference:
•
•
•
•
Pocket card (palm format downloadable from ALLHAT.ORG)
ALLHAT results paper; Setting the Record Straight paper
Newsletter
JNC7 reference card (also on CD & NHLBI.ORG)
53
Web site
www.nhlbi.nih.gov/
54
DASH Fact Sheet
55
Your Guide to Lowering
Blood Pressure
56
Reference Card
57
Thank you for your attention!
For more
information
contact the UCI
Heart Disease
Prevention
Program at:
www.heart.uci.edu
949-824-5561