Are All Antihypertensives The Same? Birju B. Patel, M.D. Geriatric Medicine Trainee Emory University School of Medicine, Division of Geriatrics June 5th, 2003 Journal Club - PowerPoint PPT Presentation

Loading...

PPT – Are All Antihypertensives The Same? Birju B. Patel, M.D. Geriatric Medicine Trainee Emory University School of Medicine, Division of Geriatrics June 5th, 2003 Journal Club PowerPoint presentation | free to download - id: 5bb0c4-ZTU2Y



Loading


The Adobe Flash plugin is needed to view this content

Get the plugin now

View by Category
About This Presentation
Title:

Are All Antihypertensives The Same? Birju B. Patel, M.D. Geriatric Medicine Trainee Emory University School of Medicine, Division of Geriatrics June 5th, 2003 Journal Club

Description:

Title: BIG Core Medical Education Presentation Author: SCS Healthcare Marketing, Inc. Last modified by: Birju B. Patel, M.D. Created Date: 2/14/1996 8:30:10 AM – PowerPoint PPT presentation

Number of Views:1070
Avg rating:3.0/5.0
Slides: 50
Provided by: SCSHealth
Category:

less

Write a Comment
User Comments (0)
Transcript and Presenter's Notes

Title: Are All Antihypertensives The Same? Birju B. Patel, M.D. Geriatric Medicine Trainee Emory University School of Medicine, Division of Geriatrics June 5th, 2003 Journal Club


1
Are All Antihypertensives The Same? Birju B.
Patel, M.D. Geriatric Medicine Trainee Emory
University School of Medicine, Division of
Geriatrics June 5th, 2003 Journal Club

2
Why did I choose this topic?
  • Deep interest in the topic of HTN
  • New guidelines (JNC VII) media coverage
  • Seemingly contradictory trials (ALLHAT vs. ANBP2)
  • Lack of BP control in most patients!
  • So many choices in medications

3
What are we going to talk about?
  • Background and impact of HTN
  • JNC VI and VII goals, recommendations
  • ALLHAT trial synopsis
  • ANBP2 trial
  • Comparison of these two trials
  • Take home lessons
  • Discussion questions

4
Background

5
First direct measurement of blood pressure
  • There was no direct means to measure the arterial
    pressure until 1733 when Stephen Hales sacrificed
    his horse in his back yard by measuring the
    height of a column of blood extending from the
    carotid artery into a glass tube from the time of
    cannulation until the horses' death.

6
1896 - Riva-Roccis first inflatable rubber cuff
7
Auscultatory method described by Korotkoff
Korotkoff, 1905
8
  • Antihypertensive agents produce no
  • obvious benefit in patients over 65
  • Fry J, Lancet 1974

9
  • Hypertensive drugs should probably not
  • be given (in the elderly) unless the blood
  • pressure is more than 200/110 mm Hg.
  • Editorial, Br Med J, 1978

10
Cardiovascular Disease is the 1 Cause of Death
in the US
2001 Heart and Stroke Statistical Update.
American Heart Association.
11
  • Prevalence of Cardiovascular Disease

Estimated Number of Persons With Cardiovascular
Disease in the US
Prevalence (millions)
10
20
30
40
50
60
(24)
50,000,000
High BP
12,200,000
CAD
4,600,000
CHF
4,400,000
Stroke
2,800,000
Other
BPblood pressure, CADcoronary artery disease,
CHFcongestive heart failure
American Heart Association . 2000 Heart and
Stroke Statistical Update. 1999.
12
A Public Health Crisis
60.8 MILLION AMERICANS HAVE CARDIOVASCULAR
DISEASE
  • High BP 50 million
  • 1 Cardiovascular Disease
  • Coronary heart disease 12.4 million
  • Myocardial infarction 7.3 million
  • Angina pectoris 6.4 million
  • Stroke 4.5 million
  • CHF 4.7 million

2001 Heart and Stroke Statistical Update.
American Heart Association.
13
Hypertension in the elderly
  • More than two-thirds of people over 65 have HTN.
  • This population has the lowest rates of BP
    control.
  • Isolated systolic HTN is common.
  • Lower initial drug doses may be used to avoid
    symptoms standard doses and multiple drugs will
    be needed to reach BP targets.

Adapted from JNC VII. JAMA. 20032982560-2572
14
Millimeters Matter...
  • A 2-mm Hg reduction in DBP would result in
    a 6 reduction in the risk
    of CHD and a 15 reduction in the risk of
    stroke and TIAs

Cook, et al. Arch Int Med. 1995155701-709.
15
Development of Antihypertensive Therapies
Effectiveness
Tolerability
1940s 1950 1957 1960s 1970s 1980s 1990s 2001
16
Treated hypertensive subjects with BP lt140/90 mmHg
17
Approximately 50 Million Americans Have
Hypertension
13.7 million
Controlled 27.4
36 million
Uncontrolled 72.6
American Heart Association, February 1999.
18
JNC VI BP Classification
BP (mm Hg)
Category Optimal Normal High-normal Hypertension
stage 1 stage 2 stage 3
Systolic ?120 ?130 130139 140159 160179 ?180
and and or or or or
Diastolic ?80 ?85 8589 9099 100109 ?110
Adapted from JNC VI. Arch Intern Med.
19971572413-2446.
19
JNC VII
BP Classification SBP mmHg DBP mmHg
Normal lt120 and lt80
Prehypertension 120139 or 8089
Stage 1 HTN 140159 or 9099
Stage 2 HTN gt160 or gt100
Approximately 45 million americans fall into
prehypertensive category
Adapted from JNC VII. JAMA. 20032982560-2572
20
Hypertension
  • The greatest danger to a man with high blood
    pressure lies in its discovery, because then some
    fool is certain to try and reduce it.
  • Brit Med J 1931243-7.

21
Lifestyle Modification
Modification Approximate SBP reduction (range)
Weight reduction 520 mmHg/10 kg weight loss
DASH eating plan 814 mmHg
sodium reduction 28 mmHg
Physical activity 49 mmHg
Moderation of alcohol 24 mmHg
Adapted from JNC VII. JAMA. 20032982560-2572.
22

New Features and Key Messages
  • For persons over age 50, SBP is a more important
    than DBP as CVD risk factor.
  • Starting at 115/75 mmHg, CVD risk doubles with
    each increment of
  • 20/10 mmHg throughout the BP range.
  • Persons who are normotensive at age 55 have a 90
    lifetime risk for developing HTN.
  • Those who are prehypertensive require
    health-promoting lifestyle modifications to
    prevent CVD.

Adapted from JNC VII. JAMA. 20032982560-2572
23
New Features and Key Messages
  • Thiazide diuretics should be initial drug therapy
    for most, either alone or combined with other
    drug classes.
  • Certain high-risk conditions are compelling
    indications for other drug classes.
  • Most patients will require two or more
    antihypertensive drugs to achieve goal BP.
  • If BP is gt20/10 mmHg above goal, initiate therapy
    with two agents, one usually should be a
    thiazide-type diuretic.

Adapted from JNC VII. JAMA. 20032982560-2572
24
Major Outcomes in High Risk Hypertensive Patients
Randomized to Angiotensin-Converting Enzyme
Inhibitor or Calcium Channel Blocker vs Diuretic
  • The Antihypertensive and Lipid-Lowering Treatment
    to Prevent Heart Attack Trial (ALLHAT)

The ALLHAT Collaborative Research Group Sponsored
by the National Heart, Lung, and Blood Institute
(NHLBI)
JAMA. 20022882981-2997
25
(No Transcript)
26
ALLHAT
  • 42,418 patients with hypertension
  • SBP gt140mmHg and/or DBP gt90 mmHg OR
  • Took medication for hypertension and had at least
    one additional risk factor for CHD
  • Age 55-79, mean age 67 yrs

Calcium Channel Blocker Amlodipine 2.5-10
mg/day (n9,048)
ACE Inhibitor Lisinopril 10-40 mg/day (n9,054)
Alpha Blocker Doxazosin 2-8 mg/day (n9,061)
Diuretic Chlorthalidone 12-25 mg/day (n15,255)
  • Endpoints
  • Primary Fatal coronary heart disease and
    nonfatal MI
  • Secondary All-cause mortality, stroke, and
    major cardiovascular disease events (CHF,
    coronary revascularization, angina, and
    peripheral artery disease)
  • Mean follow-up 4.9 years

JAMA 20022882981-2997
Discontinued prior to study completion
27
ALLHAT Primary Endpoint
Chlorthalidone vs Lisinopril Primary Endpoint RR
0.99 p 0.81
Chlorthalidone vs Amlodipine Primary Endpoint RR
0.98 p 0.65
Lisinopril
Chlorthalidone
Amlodipine
Chlorthalidone
JAMA 20022882981-2997
Primary Endpoint Fatal CHD or nonfatal MI
28
Secondary Endpoints
Chlorthalidone vs Amlodipine
All Cause Mortality RR 0.96 p 0.20
Heart Failure RR 1.38 p lt 0.001
Amlodipine
Chlorthalidone
Amlodipine
Chlorthalidone
JAMA 20022882981-2997
29
Secondary Endpoints
Chlorthalidone vs Lisinopril
All Cause Mortality RR 1.00 p 0.90
Stroke RR 1.15 p 0.02
Heart Failure RR 1.19 p lt 0.001
Chlorthalidone
Lisinopril
Chlorthalidone
Chlorthalidone
Lisinopril
Lisinopril
JAMA 20022882981-2997
30
ALLHAT Conclusions
  • Better control of systolic BP was achieved with
    chlorthalidone than with amlodipine or lisinopril
  • There were no differences in risk for CHD
    death/nonfatal MI between chlorthalidone and
    amlodipine or lisinopril
  • In secondary endpoints, chlorthalidone was
    associated with lower risk for
  • stroke, combined CVD, and HF compared with
    lisinopril
  • HF compared with amlodipine

MImyocardial infarction CHDcoronary heart
disease HFheart failure
ALLHAT Research Group. JAMA. 20022882981-2997.
31
ALLHAT Implications
  • Unless contraindicated, or unless specific
    indications are present that would favor use of
    another drug class, diuretics should be the
    initial drug of choice in antihypertensive
    regimens
  • Only 30 percent of patients achieve both systolic
    BP lt140 mmHg and diastolic BP lt90 mmHg on
    monotherapy
  • Many high-risk hypertensive patients will require
    2 or more drugs for BP control

ALLHAT Research Group. JAMA. 20022882981-2997.
32
ALLHAT Limitations
  • Add-on therapy
  • Especially atenolol not ideal and not synergistic
    for ACEI group.
  • Large crossover rate by 4 year follow-up
  • ACEI known to be less effective in blacks and
    also less well tolerated.

33
(No Transcript)
34
ANBP2 trial at a glance
  • Prospective, randomized, open-label study with
    blinded assessment of end points.
  • 6083 subjects with hypertension
  • Aged 65 to 84 years
  • 1594 family practices throughout Australia.
  • The ACE inhibitor enalapril or the diuretic
    hydrochlorothiazide were recommended as initial
    therapy however, the choice of the specific
    agent and dose was made by the family
    practitioner.

35
Inclusion criteria
  • Average systolic at least 160 mm Hg or an average
    diastolic of at least 90 mm Hg.
  • Absence of recent CV event in 6 months
  • Informed consent

36
Exclusion criteria
  • Life threatening illness
  • Contraindication to ACEI or diuretic
  • Creatinine gt 2.5 mg/dl
  • Malignant hypertension
  • Dementia

37
(No Transcript)
38
ANBP2 trial
  • To achieve the blood-pressure goals (lt160/90),
    the addition of beta blockers, calcium channel
    blockers, and alpha blockers was recommended in
    both groups.
  • Subjects were followed for a median of 4.1 years.
  • At baseline the treatment groups were similar in
    terms of age, sex, blood pressure, previous
    treatment of BP, BMI, tobacco and alcohol use,
    level of physical activity, hx of CAD, CVD, DM,
    and Hypercholestrolemia.

39
(No Transcript)
40
BP decreased to a similar extent in both groups
(a decrease of 26/12 mm Hg).
41
Table 2
  • Hazard ratio of all cardiovascular events or
    death from any cause in ACEI group vs. diuretic
    group was 0.89 (95 percent confidence interval,
    0.79 to 1.00 P0.05)
  • 11 reduction in total burden of CV events or
    death of any cause.
  • 32 subjects of either sex or 23 men need to be
    treated with ACEI to prevent one additional first
    CV event or death in first five years after
    treatment.

42
(No Transcript)
43
(No Transcript)
44
(No Transcript)
45
Limitations of ANBP2
  • Open-labeled design and lack of step up protocol
    allows bias in treatment approach
  • Limited statistical power, smaller study, lower
    risk population
  • Only 58 of ACEI group and 62 of diuretic group
    were receiving assigned treatment at end of study.

46
ALLHAT vs. ANBP2
  • Lower initial bp in ALLHAT trial vs. ANBP2
  • More caucasian (lack of black subjects) and low
    CV risk subjects in ANBP2 vs. ALLHAT (35 black
    subjects in ALLHAT)
  • More diabetics 36 in ALLHAT vs. 7 in ANBP2.
  • Open label vs. double-blinded design
  • ALLHAT trial much larger
  • ALLHAT with well defined protocol of starting
    dose, titration, and add-ons.

47
Take home points
  • ACEIs have good outcome evidence in non-black
    hypertensive patients ALLHAT
  • Low-dose thiazides have outcome advantages over
    ACEIs in black patients. ALLHAT
  • Low-dose thiazides have good outcome evidence in
    elderly patients with CV risk factors (including
    diabetes) ALLHAT
  • Low-dose thiazides good evidence in females
    ALLHAT, ANBP2

48
Take home points
  • ACEIs have good outcome evidence in caucasian
    hypertensive male patients low-dose thiazides
    also have good evidence ALLHAT given
    limitations of ANBP2 trial design.
  • ACEIs and low-dose thiazides work synergistically
    are a logical combination option in non-black
    patients
  • CAUTION very different study designs and
    population groups limit comparison

49
Collaboration can get us a long way.
About PowerShow.com