hypertension lin show pdf -...

Masked HypertensionWhy Should We Care?

Dr. Peter J. Lin Director Primary Care Initiatives - Canadian Heart Research Centre

PRESENTER DISCLOSUREFaculty: Dr. Peter Lin•Relationships with commercial interests:

•Grants/Research Support: None

•Speakers Bureau/Honoraria: Astrazeneca, BMS, Takeda, Purdue BoeringherIngelheim, Bayer, Eli Lilly, Amgen, Janssen, Forest Laboratories, J&J, Merck, Novartis, Pfizer, Servier, Sanofi, Abbott, Mylan

•Consulting Fees: Astrazeneca, Boeringher Ingelheim, Bayer, Eli Lilly, Merck, Sanofi, Amgen, MdBriefCase•Other: None

MITIGATING POTENTIAL BIAS

Potential bias was mitigated through the use of current Hypertension Canada guidelines as the primary literature source for recommendations in the slide deck.

1931 - Key Opinion Leaders :

Please do not measure the blood pressure because you

might want to treat it.

1X risk2X risk

Cardiovascular mortality risk

0

2

4

8

115/75 135/85 155/95 175/105

6

Systolic BP/Diastolic BP (mmHg)

*Individuals aged 40–69 years

4X risk

8X risk

Cardiovascular Mortality Risk Doubles with each 20/10 mmHg Increase in Systolic/Diastolic BP*

Lewington et al. Lancet 2002;360:1903–13

Staessen JA, et al. Lancet. 2001;358:1305-15.

Difference in SBP (mm Hg)Difference in SBP (mm Hg)

Odd

s R

atio

Odd

s R

atio

P = 0.003

0 5 10 15 20 25- 5

HOPE

MIDAS/NICS/VHAS

UKPDS C vs A

NORDIL INSIGHTHOT L vs H

HOT M vs HSTOP ACEIs

STOP CCBs

CAPPP UKPDS L vs HSyst-China

STONESyst-Eur

MRC1MRC2

SHEP HEPEWPHE

RCT70-80

STOP-1PART 2/SCAT

ATMH

1.50

1.25

1.00

0.75

0.50

0.25

SBP Reduction and CV Mortality

Staessen JA, et al. Lancet. 2001;358:1305-15.

Difference in SBP (mm Hg)Difference in SBP (mm Hg)

Odd

s R

atio

Odd

s R

atio

P = 0.003

0 5 10 15 20 25- 5

1.50

1.25

1.00

0.75

0.50

0.25

SBP Reduction and CV Mortality

102009 Canadian Hypertension Education Program Recommendations2009 Canadian Hypertension Education Program Recommendations

Office SBP mmHg

Hom

e or

Day

tim

e A

BP

MS

BP

mm

Hg

135 135

140

140

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

Measuring Blood Pressure


Office SBP mmHg

Hom

e or

Day

tim

e A

BP

MS

BP

mm

Hg

Truehypertensive

TrueNormotensive White Coat HTN

135

140

135

140



Stroke: Normotensive vs WCH vs Hypertensive

Verdecchia P et al. Hypertension 2005;45:203-208


Office SBP mmHg

Hom

e or

Day

tim

e A

BP

MS

BP

mm

Hg

Truehypertensive


Masked HTN

135

140

135

140




Office SBP mmHg

Hom

e or

Day

tim

e A

BP

MS

BP

mm

Hg

Truehypertensive


Masked HTN

135

140

135

140



150


Office SBP mmHg

Hom

e or

Day

tim

e A

BP

MS

BP

mm

Hg

Truehypertensive


Masked HTN

135

140

135

140



130

Prevalence of Masked Hypertension

Overall, the prevalence of masked hypertension is:

10%about

in the general population

30%about

in treated hypertensive patients

diabetesin patients with

and

higher

chronic kidney disease patients

18

20

ACCOMPLISH trial : ACEi‐CCB vs ACEi‐HCTZ

Absolute risk reduction in primary outcome events (i.e., CV death, nonfatal MI, nonfatal stroke, hospitalization for angina, resuscitation after sudden cardiac arrest, coronary revascularization): 2.2%

Absolute risk reduction in deaths from CV causes: 0.4% 1. Jamerson K, et al. N Engl J Med. 2008;359(23):2417-2428.

ACEi + HCTZ

ACEi + CCB

21

Non-persistence with AntihypertensiveTherapy Leads to Increased Risk of Myocardial Infarction or Stroke

Risk* of MI or stroke associated with nonpersistent use of antihypertensive therapy relative to 2-year persistent use

*Adjusted for gender, age, prescriber, initial antihypertensive,number of antihypertensives and other CV drugsValues in parentheses are the 95% confidence intervals Breekveldt-Postma NS, et al. 2008

1

Acute MI Stroke

1.15 (1.00–1.33)1.28 (1.15–1.45)

0

2

22

Poor Compliance is Linked to Hospitalization Risk

Level of compliance (%)

All-cause hospitalization risk† (%)

†The probability of one or more hospitalizations during a 12-month period*p<0.05 vs 80–100% compliant group

(n=350) (n=344) (n=562) (n=921) (n=5804)

Sokol MC, et al. 2005

**

*

*

4439

36

3027

0

10

20

30

40

50

1–19 20–39 40–59 60–79 80–100

The ACCORD Study Group. N Engl J Med 2010;10.1056/NEJMoa1001286

ACCORD – Blood Pressure

135 mmHg

120 mmHg

1X risk2X risk

Cardiovascular mortality risk

0

2

4

8

115/75 135/85 155/95 175/105

6

Systolic BP/Diastolic BP (mmHg)

*Individuals aged 40–69 years

4X risk

8X risk

Cardiovascular Mortality Risk Doubles with each 20/10 mmHg Increase in Systolic/Diastolic BP*

Lewington et al. Lancet 2002;360:1903–13

mmHg

ALLHAT 1

HOPE

PROGRESS

CAPPP

INSIGHT

NORDIL

HOT

STONE

STOP-2

LIFE

ALLHAT 2

ANBP2

INVEST

SCOPE

ASCOTVALUE

BP reductions achieved in recent trials

Mancia and Grassi J.Hypertension 2002 updated

130

140

150

160

170

180

190

200

SBP

Recommendations: Hypertension/ Blood Pressure Control (2)

Systolic Targets:• People with diabetes and hypertension should be

treated to a systolic blood pressure goal of <140 mmHg. A

American Diabetes Association Standards of Medical Care in Diabetes. Cardiovascular disease and risk management. Diabetes Care 2017; 40 (Suppl. 1): S75-S87


Stroke benefit


Systolic Targets:• People with diabetes and hypertension should be

treated to a systolic blood pressure goal of <140 mmHg. A

• Lower systolic targets, such as <130 mmHg, may be appropriate for certain individuals at high risk of CVD, if they can be achieved without undue treatment burden. C


mmHgmmHg

ALLHAT 1

HOPE

PROGRESS

CAPPP

INSIGHT

NORDIL

HOT

STONE

STOP-2

LIFE

ALLHAT 2

ANBP2

INVEST

SCOPE

ASCOTVALUE

BP reductions achieved in recent trials

Mancia and Grassi J.Hypertension 2002 updated

130

140

150

160

170

180

190

200

SBP

70

80

90

100

110

120

DBP

BP Control Reduces CV Events: HOT Trial

Hansson et al. Lancet. 1998;351:1755.

P<0.005

MI,

stro

ke, C

V m

orta

lity/

1000

pt-y

Diabetes SubgroupDiabetes Subgroup

90 mm Hg (n=501)85 mm Hg (n=501)80 mm Hg (n=499)

Goal of therapy: target diastolic BP24.4

18.8

11.9

30

25

20

15

10

5

0

< 80 mmHg

< 85 mmHg

Source: Hansson L et al. Lancet 1998;351:1755-1762

Hypertension Optimal Treatment (HOT) Study

Diastolic BP goal

Patients without Diabetes

Maj

or C

V ev

ents

per

1000

pat

ient

-yea

rs

Patients with Diabetes

Diastolic BP goal

18,790 patients with a baseline diastolic BP of 100-115 mm Hg randomized to a target diastolic BP of <90 mm Hg, <85 mm Hg, or <80 mm Hg

More intensive blood pressure control provides greater benefit in patients with diabetes

Blood Pressure Lowering Therapy Evidence: Effect of Intensive Blood Pressure Control

BP=Blood pressure, CV=Cardiovascular


Diastolic Targets:• Patients with diabetes should be treated to a

diastolic blood pressure <90 mmHg. A• Lower diastolic targets, such as <80 mmHg,

may be appropriate for certain individuals at high risk for CVD if they can be achieved without undue treatment burden. C


Pre SPRINT Targets

Population SBP DBPHigh Risk (SPRINT) ≤120 NADiabetes < 130 < 80All others* < 140 < 90

*Target BP with Automated Office Blood Pressure (AOBP) threshold < 135/85

Leung AA. 2016 CHEP Guidelines. Hypertension Canada’s 2016 Canadian Hypertension Education Program Guidelines for Blood PressureMeasurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can Cardio Soc 2016;32:569-588.

SPRINT Trial ACCORD Trial

• Patients (n=9361)• age ≥50 years• SBP ≥130 mm Hg• ↑CV risk (but without diabetes) • assigned to:

o SBP target <120 mm Hg (intensive treatment), oro SBP target <140 mm Hg (standard treatment)

• Primary composite outcome: MI, other acute coronary syndromes, stroke, HF, or death from CV causes

1. SPRINT Research Group. N Engl J Med 2015.

Mean SBP136.2 mm Hg

Mean SBP121.4 mm Hg

Standard

Intensive

Year 1

Number ofParticipants

Hazard Ratio = 0.75 (95% CI: 0.64 to 0.89) Standard

Intensive(243 events)

Mean Follow up = 3.26 yearsNNT=61

SPRINT Primary Outcome

(319 events)

Adapt from Figure 2B in the N Engl J Med manuscript

Include NNT

All‐cause Mortality

Standard(210 deaths)

Intensive(155 deaths)

Hazard Ratio = 0.73 (95% CI: 0.60 to 0.90)NNT = 90Median = 3.26 years

Primary Outcome Experience in the Six Pre‐specified Subgroups of Interest

*Treatment by subgroup interaction

SPRINTTreatmentAlgorithm

IntensiveTreatment May begin with a single agent for Age >75 or

Older with SBP < 140 on 0 ‐1 med at study entry. Second drugAdded at 1 month visit if asymptomatic and SBP > 130

Number (%) of Participants with aMonitored Clinical Measure During Follow‐up

Number (%) of ParticipantsIntensive Standard HR (P Value)

Laboratory Measures1

Sodium <130 mmol/L 180 (3.9) 100 (2.2) 1.76 (<0.001)Potassium <3.0 mmol/L 114 (2.5) 74 (1.6) 1.50 (0.006)Potassium >5.5 mmol/l 176 (3.8) 171 (3.7) 1.00 (0.97)

Signs and SymptomsOrthostatic hypotension2 777 (16.6) 857 (18.3) 0.88 (0.013)Orthostatic hypotension with dizziness 62 (1.3) 71 (1.5) 0.85 (0.35)

1. Detected on routine or PRN labs; routine labs drawn quarterly for first year, then q 6 months2. Drop in SBP ≥20 mmHg or DBP ≥10 mmHg 1 minute after standing (measured at 1, 6, and 12 months and yearly thereafter)

Serious Adverse Events* (SAE) During Follow‐up

All SAE reports

Number (%) of ParticipantsIntensive Standard HR (P Value)

1793 (38.3) 1736 (37.1) 1.04 (0.25)

SAEs associated with Specific Conditions of Interest

Hypotension 110 (2.4) 66 (1.4) 1.67 (0.001)Syncope 107 (2.3) 80 (1.7) 1.33 (0.05)Injurious fall 105 (2.2) 110 (2.3) 0.95 (0.71)Bradycardia 87 (1.9) 73 (1.6) 1.19 (0.28)Electrolyte abnormality 144 (3.1) 107 (2.3) 1.35 (0.020)Acute kidney injury or acute renal failure 193 (4.1) 117 (2.5) 1.66 (<0.001)

*Fatal or life threatening event, resulting in significant or persistent disability,requiring or prolonging hospitalization, or judged important medical event.

Old BP Targets




New BP Targets (Post SPRINT)




Who is a High Risk (SPRINT) Patient? Someone with any of the following:


Who is a High Risk (SPRINT) Patient? Someone with any of the following:

CVD - Clinical or sub-clinical

CKD (non-diabetic nephropathy, proteinuria <1 g/d, *eGFR 20-59 mL/min/1.73m2)

CV Risk - †Estimated 10-year global CV risk ≥15%

Age ≥ 75 years

* Four variable MDRD equation† Framingham Risk Score


How do you make it easy?Systolic ≤ 120 < 130/80 <140/90

Diabetes □CVD □CKD (eGFR 20-59) □CV Risk > 15% □Age > 75 □Nothing from list □

INVEST International Verapamil SR‐Trandolapril studyMI and Stroke based on Diastolic Blood Pressure Achieved

Ann Intern Med. 2006;144:884–893.DBP

INVEST International Verapamil SR-Trandolapril studyMI and Stroke based on Diastolic Blood Pressure Achieved

Ann Intern Med. 2006;144:884–893.DBP

Ann Intern Med. 2006;144:884–893.

Variable Mean ± SD or%

No. of diseased vessels 1 0.1%

2 16.6%

3 83.3%

Location of disease LAD 98.9%

LCX 92.6%

RCA 91.7%

Proximal LAD involvement (target lesion = LAD located in proximal)

13.8%

No. of lesions per patient 5.7 ± 2.2 (1888)

Extent of disease per patient (total length of lesions, mm) 77.6 ± 33.8 (1888)

Duke jeopardy score 9.3 ± 3.1 (1874)

LVEF (%) 66.2 ± 11.3 (1291)

LVEF >50% 90.9%

35%‐50% 8.0%

<35% 1.1%

No. of Diseased Vessels 3 - 83.3%

No. of Lesions per Patient - 5.7

Systolic ≤ 120 < 130/80 <140/90

Diabetes □CVD □CKD (eGFR 20-59) □CV Risk > 15% □Age > 75 □Nothing from list □

Measure BP Properly

Outside BP

0

20

40

60

80

100

0

0.4

0.8

1.2

1.6

2

ALLHAT Number of Pills Needed

6 mos 1 yr 3 yr 5 yr

1 Drug 2 Drugs 3 Drugs

Pat

ien

ts (

%)

Cushman WC, et al. J Clin Hypertens. 2002;4:393-405. www.hypertensiononline.org

Averag

e # of d

rug

s

Blood pressure controlled <140/90 mmHg

49.8% 55.2% 62.3% 65.6%

1.4

1.7

2.0

1.3

Single Pill Combo and adherence

1. Sherrill B, et al. J Clin Hypertens. 2011;13(12):898‐909.

Combine or Double Up?Ratio of Incremental SBP‐Lowering Effect at Standard Dose

Incr

emen

tal

SB

P r

edu

ctio

n

rati

o ob

serv

ed/

exp

ecte

d

(ad

dit

ive)

1. Wald DS, et al. Am J Med 2009;122:290

CCB = calcium channel blocker

CV risk ‐ Initial combination therapy

1. Corrao G, et al. Hypertension. 2011;58(4):566‐572.

What can you combine?

A: ACEI inhibitorsARBs

B: Beta-blockers

C: CCB

D: Diuretics

E: Everything elseDRI (Direct Renin Inhibitor)Alpha-blockers (doxazosin, terazosin)Vasodilators (hydralazine, minoxidil)Central sympatholytics (clonidine, methyldopa)

63

64

AmlodipineDilates

ACEi Dilates

AmlodipineDilates

ACEiDilates

STITCH algorithm

1. Feldman RD, et al. Hypertension. 2009;53(4):646-653.

STITCH study: Results

1. Feldman RD, et al. Hypertension. 2009;53(4):646-653.

Absolute difference: 12.0% 95% CI 1.5-22.4%P = 0.026

Thiazide/thiazide‐like* ACEI§ Long‐acting

CCB

TARGET <135/85 mmHg (automated measurement method)

ARB § Beta‐blocker†

First Line Treatment of Adults with Systolic/DiastolicHypertension Without Other Compelling Indications

Health behaviour management

Single pill combination**

† BBs are not indicated as first line therapy for age 60 and above§Renin angiotensin system (RAS) inhibitors are contraindicated in pregnancy and

caution is required in prescribing to women of child bearing potential

* Longer‐acting (thiazide‐like) diuretics are preferred over shorter‐acting (thiazide) diuretics

INITIAL TREATMENT

**Recommended SPC choices are those in which an ACE‐I is combined with a CCB,an ARB with a CCB, or an ACE‐I or ARB with a diuretic

hypertension lin show pdf -...

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