Transcript 02 WS Padwal Hypertensionx

Update on HTN and ABPM
Raj Padwal
Division of General Internal Medicine
University of Alberta
Disclosures
Funding: CIHR, AIHS, HSF, UHF
Research Collaboration: Novo Nordisk, CVRx
Consulting: Vivus, Medtronic
Speaking and other Honoraria: Abbott
Outline
1. Understand how to interpret ABPM.
2. Review the pros and cons of different
methods to diagnose hypertension.
3. Discuss some current controversies in HTN
management.
Epidemiology and Significance
European Society of Hypertension
Classification of Blood Pressure
Category
Systolic
Diastolic
Optimal
<120
and / or
<80
Normal
<130
and / or
<85
High-Normal
130-139
and / or
85-89
Grade 1 (mild hypertension )
140-159
and / or
90-99
Grade 2 (moderate hypertension)
160-179
and / or
100-109
Grade 3 (severe hypertension)
 180
and / or
 110
Isolated Systolic Hypertension (ISH)
140
and
<90
The category pertains to the highest risk blood pressure
*ISH=Isolated Systolic Hypertension.
J Hypertens 2007;25:1105-87.
Hypertension in Canada:
Prevalence and Control
Overall prevalence is 21%
McAlister et al. CMAJ 2011
Life time risk of Hypertension in Normotensive
Women and Men aged 65 years
Risk of Hypertension %
Risk of Hypertension %
100
100
Women
80
80
60
60
40
40
20
20
0
0
2
4
6
8
10
12
14
Years to Follow-up
16
18
20
0
Men
0
2
4
6
8
10
12
14
16
18
20
Years to Follow-up
JAMA 2002: Framingham data.
Diagnosing Hypertension
Blood Pressure Assessment:
Patient preparation and posture
Standardized Preparation:
Patient
1. No acute anxiety, stress or pain.
2. No caffeine, smoking or nicotine in the preceding
30 minutes.
3. No use of substances containing adrenergic
stimulants such as phenylephrine or
pseudoephedrine (may be present in nasal
decongestants or ophthalmic drops).
4. Bladder and bowel comfortable.
5. No tight clothing on arm or forearm.
6. Quiet room with comfortable temperature
7. Rest for at least 5 minutes before measurement
8. Patient should stay silent prior and during the
procedure.
II. Criteria for the diagnosis of hypertension and
recommendations for follow-up
BP: 140-179 / 90-109
Clinic BP
ABPM (If available)
Home BPM
Hypertension visit 3
>160 SBP or
>100 DBP
<160 / 100
Diagnosis
of HTN
or
ABPM or HBPM
Awake BP
<135/85
and
24-hour
<130/80
Awake BP
>135 SBP or
>85 DBP or
24-hour
>130 SBP or
>80 DBP
Continue to
follow-up
Diagnosis
of HTN
Hypertension visit 4-5
>140 SBP or
>90 DBP
< 140 / 90
Diagnosis
of HTN
Continue to
follow-up
< 135/85
>135/85
Confirm
with repeat
Home BPM
or ABPM
Continue to
follow-up
Diagnosis
of HTN
Patients with high normal blood pressure (clinic SBP
130-139 and/or DBP 85-89) should be followed annually.
Clinic, Home, Ambulatory (ABP) Blood
Pressure Measurement Equivalence Numbers
A clinic blood pressure of 140/90 mmHg has a
similar risk of a:
Description
Blood Pressure mmHg
Home pressure average
135 / 85
Daytime average ABP
135 / 85
24-hour average ABP
130 / 80
ABPM Indications
Chughtai and Peixoto. Hosp Phys 2003
Contraindications to ABPM
1. Not cooperative
2. Severe PVD or thrombocytopenia
3. Afib (relative): not accurate
4. Arm too big
5. Severe office HTN (≈220/120)
ABPM 1
ABPM 1
Information Provided by ABPM
1. Estimate of true overall 24 hour BP
2. Diurnal variation in BP
3. Variability in BP
4. Duration of action of drug
ABPM Normal Parameters
BP should dip by 10-20% during sleep
Chughtai and Peixoto. Hosp Phys 2003
ABPM 2
ABPM 2
ABPM 3
ABPM 3
ABPM 4
ABPM: Number of Readings
• Recommendation is at least 14 readings in the
daytime (NICE Guidance).
• Minimum number is 2 per hour.
• We usually do a reading an hour at night.
ABPM 5
ABPM 5
ABPM 5
Ziemmsen. J Neurol Sci 2010
White Coat and Masked Hypertension
Home/Ambulatory SBP mmHg
200
180
160
Masked
Hypertension
Hypertension
140
135
120
White Coat
Hypertension
Normotension
100
100
120
140
160
180
200
Office SBP mmHg
Derived from Pickering et al. Hypertension 2002: 40: 795-796
Prognosis of Masked Hypertension
Prevalence of masked hypertension is approximately 10% in the general population but is
higher in patients with diabetes
J Hypertension 2007;25:2193-98
Prognostic Significance of Clinic vs.
ABPM
Dawes. BP Monit 2006
Prognostic Significance of Clinic vs.
ABPM
Dawes. BP Monit 2006
Diagnostic Utility of BP Measures
NICE 2011 Guidance Document
Diagnostic Utility of BP Measures
Hodgkinson. BMJ 2011
Cost-Effectiveness of ABPM
Lovibond. Lancet 2011
Diagnosis of Hypertension: Key
Points
• Non-automated office BP measurements are
not accurate.
• This results in inappropriate management.
• Out-of-office measurement – particularly
ABPM – should be used to confirm the
diagnosis of HTN.
Bedtime Dosing of
Antihypertensive Drugs
Predictive Role of Nighttime BP
Hansen. Hypertension 2012
The MAPEC Trial
MAPEC
Hypothesis: Bedtime chronotherapy leads to better
BP control and reduces CV endpoints.
Design: PROBE RCT
Country: Spain
Sample Size: 2156; mean age 56
Endpoints:
1. All-cause mortality and CVD events (huge
composite endpoint)
2. 48-hour ABPM
MAPEC: Results
Baseline awake systolic ABPM was 134 mm Hg.
Baseline asleep systolic ABPM was 123 mm Hg.
MAPEC: Results
MAPEC Study: Issues
• Inconsistent numbers presented across trial
publications. Is this truly an RCT with a
predefined start and end? Original sample size in
the protocol was 3344. Subsequent publication
mentions 734 normotensive subjects – uncertain
if they are included in the main paper.
• Most of the literature in the field comes from a
single centre and one group of investigators.
• Huge effect size from such a small, simple
change.
Bottom Line: Bedtime Dosing
• Practical point: relatively simple ‘intervention’
• Conversely, I don’t view the data as definitive
yet.
• I don’t routinely do it; however, I will in
refractory hypertension. Also, in this group, I
often use drugs that need bedtime dosing
(alpha blockers and some CCBs).
Choice of ‘Thiazide’ Diuretic for
HTN
Chlorthalidone vs. HCTZ
Pharmacologic Structure
• Chlorthalidone is often
mislabeled as ‘thiazidelike’.
• It is a non-thiazide with a
distinct pharmacological
structure….
• ….that has similar
pharmacological action
(DCT NaCl symporter
blockade)
Kurtz. Hypertension 2012.
Thiazides and Non-thiazides
Thiazides
Hydrochlorothiazide
Chlorothiazide
Methychlothiazide
Polythiazide
Bendroflumethiazide
Non-thiazides
Chlorthalidone
Indapamide
Metolazone
Pharmacokinetics
DRUG
ONSET
(h)
PEAK
T1/2 (h)
Duration (h)
HCTZ
2
4-6
6-9 (single)
8-15 (long
term)
12 (single)
16-24 (long
term)
2-6
40 (single)
45-60 (long
term)
24-48
(single)
48-72 (long
term)
Chlorthalidone 2-3
Carter BL. Hypertension 2004;43:4-9
BP Control
• Meta-analysis of 108
HCTZ and 20
chlorthalidone studies
(n=10443)
• Comparisons are indirect,
not head-to-head
Dose
• Chlorthalidone is a more
potent drug
Ernst, ME. Am J Hypertens. 2010
MRFIT Trial Results
MRFIT. JAMA 1986
Trial Results
Trial
Drug
Result
MRFIT
Both
+
HDFP
Chlorthalidone
+
ALLHAT
Chlorthalidone
+
SHEP
Chlorthalidone
+
Oslo BP
HCTZ
-
MAPHY
HCTZ
-
MRC
HCTZ
-
Wing
HCTZ
-
Amery
HCTZ
+
MIDAS
HCTZ
+
ANBP
HCTZ
+
INSIGHT
HCTZ
+
ACCOMPLISH
HCTZ
-
Diuretic Choice: Summary
• Thiazides and non-thiazides are similar and
dissimilar properties.
• Chlorthalidone (non-thiazide) is more potent
and can reduce BP more than HCTZ at equal
doses.
• Non-definitive ‘hard outcome’ indirect
comparisons: ?chlorthalidone better
Diuretic Choice: Practical
Considerations
• Chlorthalidone: smallest dose available in Canada is 50 mg.
• Chlorthalidone: not commonly available in combos
(atenolol only). HCTZ: many combos
• If BP controlled on HCTZ, I don’t change. If I need to
choose a fixed dose combo with a diuretic, I use perindopril
indapamide or a HCTZ combo ($$ and coverage considered)
• In uncontrolled refractory hypertension, I will usually use
chlorthalidone
Treatment Target in Mild HTN
Treatment of Mild Hypertension
Treatment of Mild Hypertension
Treatment of Mild Hypertension
Primary Prevention Subjects with Mild HTN
Total events 77 vs 90: Nearly all from one study
Diao et al. Cochrane Collaboration 2013
Comments on This Review
1. Essentially reflects one study (that used BB in
half the active treatment group)
2. Underpowered – study not designed to
specifically look at this subgroup.
Randomization not stratified for this subgroup.
3. The authors excluded relevant studies:
a) Non-placebo controlled studies (e.g., HDFP).
b) Didn’t have data for some studies (VA, Oslo, others)
but number of events for these would have been
small
Major Trials Including Patients with Mild
Hypertension
Trial (n)
Age
BP
Results for Primary Endpoint
(intervention vs. control)
MRC
17354
5y
35-64
Stroke events: 60 vs 109
0.14 vs. 0.26 per 100 pt*y
p<0.01
ARD 0.12% over 5 y
ANBP
3427
4y
30-70
HDFP
10940
5y
30-69
90-109
95-109
≥ 90
Nonfatal and fatal CV events:138 vs 168
2.0 vs. 2.5 per 100 pt*y
P<0.05
ARD 0.5% over 4 y
Total mortality: 349 vs. 419
6.4% vs. 7.7%
P<0.01;
ARD 1.3% over 5 y
Major Trials Including Patients with
Mild Hypertension
Trial (n)
Age
BP
Results for Primary Endpoint
(intervention vs. control)
HDFP
7825
30-69
Total mortality: 231 vs. 291
5.9% vs. 7.4%
P<0.01;
ARD 1.5%
90-104 stratum
HDFP Mortality RRR
HDFP. JAMA 1971
Canadian Hypertension Education Program
Recommendations For Initiating Drug Therapy
1. Prescribe for DBP ≥ 100 or SBP ≥ 160 (Grade
A).
2. Strongly consider for DBP ≥ 90 and TOD or
other CV risk factors (Grade A).
3. Strongly consider for SBP ≥ 140 and TOD
(Grade C for mild HTN).
Major Trials Including Patients with Mild
Hypertension
Trial (n)
Age
BP
Results for Primary Endpoint
(intervention vs. control)
NNT over 1 year
NNT over 10 y
MRC
17354
5y
35-64
Stroke events: 60 vs 109
0.14 vs. 0.26 per 100 pt*y
p<0.01
ARD 0.12% over 5 y
4167
416
ANBP
3427
4y
30-70
Nonfatal and fatal CV
events:138 vs 168
2.0 vs. 2.5 per 100 pt*y
P<0.05
ARD 0.5% over 4 y
800
80
HDFP
10940
5y
30-69
Total mortality: 349 vs. 419
6.4% vs. 7.7%
P<0.01;
ARD 1.3% over 5 y
385
39
90-109
95-109
≥ 90
NNT over 10y for statins for CV event in high-risk patient is 11 and in mod risk pt. is 23.
Major Trials Including Patients with
Mild Hypertension
Trial (n)
Age
BP
Results for Primary
Endpoint
(intervention vs. control)
NNT over NNT over 10 y
1 year
HDFP
subgroup
7825
30-69
Total mortality: 231 vs. 291
5.9% vs. 7.4%
P<0.01;
ARD 1.5%
333
90-104
stratum
33
HDFP Trial
Alderman. Hypertension 1983
II. Indications for Pharmacotherapy
after diagnosis of hypertension (1)
• Patients at low risk with stage 1 hypertension (140159/90-99 mmHg)
– lifestyle modification can be the sole therapy.
• Patients with target organ damage (e.g. left
ventricular hypertrophy) (140-159/90-99 mmHg)
– Treat with pharmacotherapy
• Patients with chronic kidney disease should be
considered for pharmacotherapy if the blood pressure
is equal or over 140/90 mmHg
• Patients with diabetes should be considered for
pharmacotherapy if the blood pressure is equal or
over 140/90 mmHg
II. Indications for Pharmacotherapy
after diagnosis of hypertension (2)
• Patients with other risk factors (over 90% of Canadians
with hypertension have other risk factors) (140-159/9099 mmHg despite lifestyle modification)
– Treat with pharmacotherapy
• Treatment Gap Alert: Many younger hypertensive
Canadians with multiple cardiovascular risks are
currently not treated with pharmacotherapy. Health care
professionals need to be aware of this important care
gap and recommend pharmacotherapy.
Treatment of Mild Hypertension: Key
Points
1. All patients should be treated with lifestyle
modification.
2. Decision to institute drug treatment should
take into account global risk.
Renal Denervation
Resistant Hypertension
• Failure to achieve BP target despite treatment
with three antihypertensive drugs (including a
diuretic) at optimal doses.
• Prevalence is not well studied. Appears to be
about 10-20% of hypertensive patients.
Sarafidis. J Clin Hypertens 2011
Sympathectomy for Severe
Hypertension
Bilateral T8-L3
Sympathectomy
Ray BS. Ann Surg 1949
Renal Sympathetic Denervation
Papademetriou et al. Int J Hypertens 2011
Renal Sympathetic Denervation for Resistant
Hypertension
Source: Medtronic
73
Renal Sympathetic Denervation for Resistant
Hypertension: SYMPLICITY HTN-2 RCT
6 month BP difference of 33/11
P<0.0001 (n=106)
Esler et al. Lancet 2010
74
Renal Sympathetic Denervation: Safety
• Well tolerated – one femoral pseudoaneurysm was the
only adverse effect. Renal function similar at end of six
months.
• Only half had ABPM measured; ABPM difference was
16/8 mm Hg between groups.
• Irreversible nature of the procedure
• Renal adverse effects?
– Stenosis, dilation
– Proteinuria
– Renal function
Renal Sympathetic Denervation: Key Point
• An emerging procedure
• Potential to be used in a large number of
patients
• Long-term efficacy and safety data required.
Outline
1. Understand how to interpret ABPM.
2. Review the pros and cons of different
methods to diagnose hypertension.
3. Discuss some current controversies in HTN
management.