Update on HTN and ABPM

Raj PadwalDivision 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

McAlister et al. CMAJ 2011

Overall prevalence is 21%

Life time risk of Hypertension in Normotensive Women and Men aged 65 years

Risk of Hypertension %

0 2 4 6 8 10 12 14 16 18 20

Years to Follow-up

Women

Risk of Hypertension %

Years to Follow-up

0 2 4 6 8 10 12 14 16 18 20

Men

JAMA 2002: Framingham data.

100

80

60

40

20

0

100

80

60

40

20

0

Diagnosing Hypertension

Blood Pressure Assessment:Patient preparation and posture

Standardized Preparation:

Patient1. 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 measurement8. 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

ABPM (If available)

Diagnosisof HTN

Awake BP>135 SBP or>85 DBP or

24-hour>130 SBP or

>80 DBP

Awake BP<135/85

and24-hour<130/80

Continue to follow-up

Clinic BP

Diagnosisof HTN

Hypertension visit 3

>160 SBP or >100 DBP

>140 SBP or>90 DBP

< 140 / 90

Diagnosisof HTN

Continue to follow-up

<160 / 100

Hypertension visit 4-5

ABPM or HBPMor

Home BPM

>135/85 < 135/85

Diagnosisof HTN

Continue to follow-up

Patients with high normal blood pressure (clinic SBP 130-139 and/or DBP 85-89) should be followed annually.

Confirm with repeat Home BPM or ABPM

Clinic, Home, Ambulatory (ABP) Blood Pressure Measurement Equivalence Numbers

Description Blood Pressure mmHg

Home pressure average 135 / 85

Daytime average ABP 135 / 85

24-hour average ABP 130 / 80

A clinic blood pressure of 140/90 mmHg has a similar risk of a:

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

Chughtai and Peixoto. Hosp Phys 2003

BP should dip by 10-20% during sleep

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

Derived from Pickering et al. Hypertension 2002: 40: 795-796

Office SBP mmHg

Ho

me/

Am

bu

lato

ry S

BP

mm

Hg

Hypertension

Normotension White CoatHypertension

MaskedHypertension

200

180

160

140

120

100

100 120 140 160 180 200

135

Prognosis of Masked Hypertension

J Hypertension 2007;25:2193-98

Prevalence of masked hypertension is approximately 10% in the general population but is higher in patients with diabetes

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

MAPECHypothesis: Bedtime chronotherapy leads to better

BP control and reduces CV endpoints.Design: PROBE RCTCountry: SpainSample 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 ‘thiazide-like’.

• 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

ThiazidesHydrochlorothiazideChlorothiazideMethychlothiazidePolythiazideBendroflumethiazide

Non-thiazidesChlorthalidoneIndapamideMetolazone

Pharmacokinetics

Carter BL. Hypertension 2004;43:4-9

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)

Chlorthalidone 2-3 2-6 40 (single)45-60 (long term)

24-48 (single)48-72 (long term)

BP Control

• Meta-analysis of 108 HCTZ and 20 chlorthalidone studies (n=10443)

• Comparisons are indirect, not head-to-head

• Chlorthalidone is a more potent drugDose

Ernst, ME. Am J Hypertens. 2010

MRFIT Trial Results

MRFIT. JAMA 1986

Trial ResultsTrial 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

Diao et al. Cochrane Collaboration 2013

Total events 77 vs 90: Nearly all from one study

Primary Prevention Subjects with Mild HTN

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) AgeBP

Results for Primary Endpoint(intervention vs. control)

MRC173545y

35-64

90-109

Stroke events: 60 vs 1090.14 vs. 0.26 per 100 pt*y p<0.01 ARD 0.12% over 5 y

ANBP34274y

30-70

95-109

Nonfatal and fatal CV events:138 vs 1682.0 vs. 2.5 per 100 pt*yP<0.05ARD 0.5% over 4 y

HDFP109405y

30-69

≥ 90

Total mortality: 349 vs. 4196.4% vs. 7.7%P<0.01; ARD 1.3% over 5 y

Major Trials Including Patients with Mild Hypertension

Trial (n) AgeBP

Results for Primary Endpoint(intervention vs. control)

HDFP7825

30-69

90-104 stratum

Total mortality: 231 vs. 2915.9% vs. 7.4%P<0.01; ARD 1.5%

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) AgeBP

Results for Primary Endpoint(intervention vs. control)

NNT over 1 year NNT over 10 y

MRC173545y

35-64

90-109

Stroke events: 60 vs 1090.14 vs. 0.26 per 100 pt*y p<0.01 ARD 0.12% over 5 y

4167 416

ANBP34274y

30-70

95-109

Nonfatal and fatal CV events:138 vs 1682.0 vs. 2.5 per 100 pt*yP<0.05ARD 0.5% over 4 y

800 80

HDFP109405y

30-69

≥ 90

Total mortality: 349 vs. 4196.4% vs. 7.7%P<0.01; ARD 1.3% over 5 y

385 39

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) AgeBP

Results for Primary Endpoint(intervention vs. control)

NNT over 1 year

NNT over 10 y

HDFPsubgroup7825

30-69

90-104 stratum

Total mortality: 231 vs. 2915.9% vs. 7.4%P<0.01; ARD 1.5%

333 33

HDFP Trial

Alderman. Hypertension 1983

II. Indications for Pharmacotherapyafter diagnosis of hypertension (1)

• Patients at low risk with stage 1 hypertension (140-159/90-99 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 Pharmacotherapyafter diagnosis of hypertension (2)

• Patients with other risk factors (over 90% of Canadians with hypertension have other risk factors) (140-159/90-99 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

73

Renal Sympathetic Denervation for Resistant Hypertension

Source: Medtronic

74

Renal Sympathetic Denervation for Resistant Hypertension: SYMPLICITY HTN-2 RCT

Esler et al. Lancet 2010

6 month BP difference of 33/11P<0.0001 (n=106)

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.